75N91021R00007 All Attachments.pdf

Attachment 1 eCPS – dated 11/20/2020

PACKAGING AND DELIVERY OF PROPOSAL ATTACHMENT 1

September 28, 2016 Page 1 of 2

Attachment 1 - Packaging and Delivery of Proposals for Use with the NIH electronic Contract Proposal Submission (eCPS) Website

I. PROPOSAL SUBMISSION

A. eCPS

1. Proposals must be submitted via the electronic Contract Proposal Submission (eCPS) website at https://ecps.nih.gov.

2. Proposals submitted by facsimile or e-mail will not be accepted.

3. Follow the “How to Submit an Electronic Proposal” instructions provided on the eCPS website at: https://ecps.nih.gov/home/howto. Please note that creating an account to submit may take up to three (3) business days. Please apply for a new account early to allow enough time for the registration process.

4. Offerors are solely responsible for submitting proposals and any modifications or revisions so as to reach the Government office designated above by the date and time specified in the solicitation. If your proposal is not received by the date and time specified in the solicitation, it will be considered a “late proposal,” in accordance with FAR 52.215-1, Instructions to Offerors- Competitive Acquisitions and HHSAR 352.215-70, Late Proposals and Revisions (December 18, 2015).

B. Creating and Naming Files:

1. Create one PDF file of your Technical Proposal, including all attachments. The

Technical Proposal should be created in a PDF format that enables word searches to the maximum extent practicable. Forms and/or documents requiring signature(s) may be scanned, but must be merged into the Technical Proposal PDF file.

2. Create one PDF file of your Business Proposal, including all attachments: The Business Proposal should be created in a PDF format that enables word searches to the maximum extent practicable. Forms and/or documents requiring signature(s) may be scanned, but must be merged into the Business Proposal PDF file. Additionally, the “Breakdown of Proposed Estimated Costs (plus Fee) with Excel Spreadsheet” (http://oamp.od.nih.gov/sites/default/files/DGS/contracting-forms/spshexcl_dec2012.xlsx) must be included in the Business Proposal.

3. Create your Business Document Excel. The Excel file should be the “Breakdown of Proposed Estimated Costs (plus Fee) with Excel Spreadsheet” (http://oamp.od.nih.gov/sites/default/files/DGS/contracting-forms/spshexcl_dec2012.xlsx) included in the Business Proposal in its original Excel format, not PDF. Multiple Excel files may be included, as necessary.

4. Each of the proposals, Technical and Business, must be separate and complete in itself.

Do not reference one proposal in another.

https://ecps.nih.gov/ https://ecps.nih.gov/home/howto http://oamp.od.nih.gov/sites/default/files/DGS/contracting-forms/spshexcl_dec2012.xlsx http://oamp.od.nih.gov/sites/default/files/DGS/contracting-forms/spshexcl_dec2012.xlsx http://oamp.od.nih.gov/sites/default/files/DGS/contracting-forms/spshexcl_dec2012.xlsx http://oamp.od.nih.gov/sites/default/files/DGS/contracting-forms/spshexcl_dec2012.xlsx

Attachment 1 eCPS – dated 11/20/2020

PACKAGING AND DELIVERY OF PROPOSAL ATTACHMENT 1

September 28, 2016 Page 2 of 2

5. File naming convention: It is requested that the filenames for your Technical Proposal, Business Proposal, and Excel Workbook include the name of the offeror, the solicitation number and the type of proposal (i.e., Technical, Business, or Excel Workbook).

Examples:

Technical Proposal: XYZ Company_NIHAI2012001_Technical.pdf Business Proposal: XYZ Company_NIHAI2012001_Business.pdf Excel Workbook: XYZ Company_NIHAI2012001_Business.xlsx

II. FORMATTING AND PAGE LIMITATIONS

A. Formatting for proposals

1. Proposal page layout shall be letter size 8.5” x 11” for all pages.

2. Proposals shall not include links to internet web site addresses (URLs) or otherwise direct readers to alternate sources of information.

3. Proposals shall not include audio or video files of any type.

4. Font size must be 10 to 12 points.

5. Spacing should be no more than 15 characters per inch. Within a vertical inch, there must be no more than six lines of text.

6. Margins must be at least one-inch on all sides.

7. Failure to adhere to the formatting requirements above may impact whether your proposal is reviewed in its entirety.

B. Page limitations:

1. The total page count of the Technical proposal shall not exceed 150 pages. Proposal pages shall be numbered "Page 1 of 150, "Page 2 of 150" etc. The page Limits for the Technical Proposals excludes any sample task order proposals and the proposal for Task Order # 1 Kick-Off meeting. The total page count for Technical proposals for the Task Order and each Sample Task Orders shall not exceed 10 pages (per task order/sample task order). Pages in excess of this limitation will be removed form the proposal and will not be provided to the reviewers to read or evaluate.

2. Total page count does not include: Title and Back Page; Table of Contents, Resumes, Appendixes & Attachments; and Section Dividers that do not contain information other than title of Section.

3. Pages in excess of this limitation will be removed from the proposal and will not be considered.

PROPOSAL INTENT RESPONSE FORM

RFP No:

RFP Title:

Please review the Request for Proposal (RFP). Furnish the information requested below and return this page to the Contracting Officer/Contract Specialist identified on Section A-Solicitation/Contract Form by

Your expression of intent is not binding but will greatly assist us in planning for proposal evaluation.

Choose one of the following Options:

Do intend to submit a proposal Do Not intend to submit a proposal

If you are not responding to this RFP, please provide your reason(s):

Please provide the following contact information:

Name (First, Middle Initial, Last):

Title:

Organization:

E-mail:

Attachment 1 – Statement of Work (SOW) PK IDIQ Base 11/19/2020

Statement of Work PK IDIQ Base

Title: Preclinical Pharmacokinetic and Pharmacology Evaluations of Agents Being Developed for Cancer Patients

Independently and not as an agent of the Government, the Contractor shall furnish all of the necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government, as required to perform the work stated below in accordance with laboratory protocols developed by the National Cancer Institute’s (NCI) Contracting Officer’s Representative (COR).

SCOPE

The Contractor shall characterize the pharmacokinetics and other pharmacological properties of investigational and approved agents being developed for the treatment of cancer.

TASKS

Compounds under evaluation will vary in their stage of development and in their requirements for evaluation. Therefore, Task Orders specific for each compound (or series of compounds) will be awarded to perform one or more of the following tasks as specified on the individual task order, such as:

1. Implement and validate analytical methodologies that are sufficiently sensitive, specific, and reproducible for measurement and quantitation of assigned test agents (e.g., drug-like small molecules and well-characterized biologicals) and their metabolites in body fluids and/or tissues of animals and tissues of humans at therapeutic and/or toxic concentrations.

2. Conduct pharmacokinetic evaluations in animals (e.g., mice, rats, tumor-bearing rodents, optionally larger animals) to support early lead and candidate drug characterizations. Various routes of administration (e.g., intravenous, oral, intraperitoneal, subcutaneous, continuous infusion, etc.)

may be utilized. Studies may include collection of multiple blood samples to obtain plasma or serum and, in some studies, collection of urine, feces, tissues or tumor samples. Detailed experimental protocols will be developed by the COR and if needed, modified following input from the contractor.

3. Utilize established analytical methods/protocols to determine concentrations of test agents in various matrices (cell extracts, media, plasma, urine, bile, saliva, tumors, and normal tissues) that may be obtained from:

(a) Pharmacokinetic evaluations conducted under item 2 above

(generated in-house);

(b) Other Government laboratories; and/or

(c) human materials/samples from clinical trials (de-identified of patient Personally Identifiable Information or PII)

4. Use state-of-the-art modeling software to fit concentration vs. time data

(for plasma and possibly tissues) to suitable non-compartmental and/or compartmental pharmacokinetic models and calculate relevant pharmacokinetic parameters (e.g., half-life, volume of distribution, area under the curve, clearance, etc.) for a given agent and route of administration.

5. Calculate systemic bioavailability for various routes (e.g., oral, ip, sc) and determine (as requested) if bioavailability is dose-dependent. Calculate mass-balance parameters when sufficient data are collected.

6. Determine the suitability of standard formulation strategies for the administration of test agents to animals by the desired route and at the desired dose level(s).

7. Determine the in vitro plasma protein binding and stability of test agents in biological fluids and tissues using standard techniques.

8. Carry out pharmacokinetic-pharmacodynamic (PK-PD) study protocols using tumor-bearing mice and collect plasma, tissue, and/or tumor samples for drug level determinations and analysis of specified pharmacodynamic endpoints.

9. Utilize standard mass spectroscopic techniques to characterize the metabolites and/or degradation products of test agents present in blood, plasma, urine, and/or other fluids. The extent of metabolite characterization will be specified by the NCI COR in the Task Order.

10. Characterize the plasma and tissue pharmacokinetics of major metabolites.

11. Store samples generated in-house or received from other laboratories under suitable conditions and ship samples to other laboratories upon request by the NCI COR.

The Contractor shall adhere to the following requirements for all task orders issued under the base contract:

A. PROJECT MANAGEMENT

Unless otherwise specified in an individual task order, the Contractor shall engage in the following project management tasks:

1. Task Order Initiation Meeting and/or Teleconference:

a. Within 10 calendar days after the effective date of the Task Order or before the start of any tasks, the Contractor shall plan for and participate in an Initiation Meeting or Teleconference to review the Task Order requirements and timelines, discuss Task Order technical plans and approaches, and identify any anticipated problems/obstacles to completing the Task Order requirements. The Task Initiation Meeting shall be attended by Contractor key personnel (including subcontractor personnel as appropriate), the COR, and other representatives at the discretion of the COR (e.g., CO, Subject Matter Experts, investigator representatives).

2. Progress Review Meetings and Teleconferences

a. The Contractor shall plan and participate in Progress Review Meetings or Teleconferences, which shall be attended by Contractor key personnel (including subcontractor personnel as appropriate), the COR, the Contracting Officer, and other individuals designated by the COR (e.g., Subject Matter Experts, investigator representatives), as necessary or as issues arise. The purpose of these meetings/teleconferences shall be to review and discuss:

1) ongoing and planned activities, protocols, and associated data;

2) timelines for task initiation and completion, submission of data, and other information;

3) any problems or deficiencies identified with respect to the accuracy, timeliness, and completeness of data submitted; and

4) any other matters relevant to the technical and financial administration of the task.

b. Key personnel or other senior staff coordinator(s) shall be available for ad hoc meetings/teleconferences with the COR immediately upon a meeting request.

B. HEALTH AND SAFETY PLAN

Each agent provided to the contractor will be considered potentially hazardous. Therefore, all necessary precautions must be taken to protect personnel and the environment against possible exposure to the agents being tested. The Contractor shall perform all work associated with this contract in accordance with all applicable Federal, State and local regulations including transportation and disposal of hazardous waste.

C. ACCESS TO DATA

The Government requires that all data accumulated under the projected contracts be immediately available for its review and those provisions are made to maintain confidentiality of all data. Authority to release data may be granted only by the Contracting Officer together with the COR and must be in writing. Upon request, individual animal data should be provided to the COR in a format that allows integration into Developmental Therapeutics Program (DTP) databases. Excel or other tab delimited file formats for are acceptable.

Other formats will be considered but compatibility shall be confirmed.

D. Section 508 – ICT Accessibility Requirements

Section 508 of the Rehabilitation Act, as amended by the Workforce Investment Act of 1998 (P.L. 105-220) requires that when Federal agencies develop, procure, maintain, or use Information and Communication Technology (ICT), it shall be accessible to people with disabilities. Federal employees and members of the public who have disabilities must have access to, and use of, information and data that is comparable to people without disabilities.

Products, platforms and services delivered as part of this work statement that are ICT, or contain ICT, must conform to the Revised 508 Standards, which are located at 36 C.F.R. § 1194.1 & Apps. A, C & D, and available at https://www.access-board.gov/guidelines-and-standards/communications-and-it/about-the-ict-refresh/final-rule/text-of-the-standards-and-guidelines Section 508 Conformance (as outlined in the attached Word document) of electronic documents shall be determined or confirmed by successful completion and submission of the relevant checklists and acceptance by NCI. Fillable versions of the GSA Section 508 Create Accessible Products may be downloaded at https://www.section508.gov/create and/or HHS’s Making Files Accessible shall be provided to the selected offeror upon initiation of this contract. NCI retains the right to confirm the accessibility and Section 508-conformance of vendor submitted documents and to return them for remediation, at no cost to the National Cancer Institute but at the contractor’s expense.

Any and all reports (including monthly and ad-hoc reports) shall be formatted for Section 508-conformance and accessibility for persons with disabilities.

Instructions may be found at HHS Making Files Accessible and at GSA Section508.gov Create Accessible Digital Products. The respective checklists from either of these sites will be considered acceptable.

All reports required herein shall be submitted in electronic format.

All electronic reports submitted shall be compliant with Section 508 of the Rehabilitation Act of 1973. Additional information about testing documents for Section 508 compliance, including guidance and specific checklists, by application, can be found at: http://www.hhs.gov/web/508/index.html under "Making Files Accessible."

https://www.access-board.gov/guidelines-and-standards/communications-and-it/about-the-ict-refresh/final-rule/text-of-the-standards-and-guidelines https://www.access-board.gov/guidelines-and-standards/communications-and-it/about-the-ict-refresh/final-rule/text-of-the-standards-and-guidelines https://www.section508.gov/create https://www.section508.gov/create https://www.hhs.gov/web/section-508/making-files-accessible/index.html https://www.hhs.gov/web/section-508/making-files-accessible/index.html https://www.hhs.gov/web/section-508/making-files-accessible/index.html https://section508.gov/create https://section508.gov/create http://www.hhs.gov/web/508/index.html

RFP 75N91021R00007

Attachment 4- Task Order #1 Statement of Work (11/20/20)

TASK ORDER #1 Request for Proposals & Statement of Work

Kick-off Meeting with NCI Staff NOTE: This Task Order will be funded upon award for each contract resulting from solicitation No.

75N91021R00007

A. Task Order Title: - “Contract Orientation and Kickoff Meeting”

B. Task Order Number – TORFP #1

C. Background and Task Order Statement of Work: The purpose of this task order is to hold an orientation/kickoff meeting to discuss Standard operating Procedures (SOP) for all Contractors awarded an Indefinite Delivery, Indefinite Quantity (ID/IQ) contract for the Division of Cancer Treatment and Diagnosis (DCTD) under the “Preclinical Pharmacokinetic and Pharmacology Evaluations of Agents Being Developed for Cancer Patients” pool.

The contractor shall budget for all key personnel and business representatives who will be most involved in contract activities to attend a webinar orientation/kickoff meeting with the National Cancer Institute (NCI) on or about 6/21/2021. It is anticipated the duration of the meeting will be not more than one hour. The contractor can comment on their capabilities and experience, but a formal presentation is not required.

During the meeting, the NCI will present overarching goals of the contract, reporting requirements, invoicing requirements, scheduling, and future task orders. Contractors will be able to ask specific questions and discuss contracting procedures at this meeting.

No technical proposal is required for this task order; however, a detailed budget proposal indicating all costs associated with the subject task order must be submitted.

D. Reporting Requirements and Deliverables: NONE

E. Proposal Due Date: Proposals are due by 4:00 PM ET on January 4, 2021 in an electronic format through the NIH electronic Contract Proposal Submission (eCPS) Website. Please reference Attachment 1 of the RFP titled “Packaging and Delivery of Proposals for Use with the NIH electronic Contract Proposal Submission (eCPS) Website,” for proposal submission instructions.

The National Cancer Institute reserves the right to make a single award, multiple awards, or no award.

In addition, changes might occur as a result of availability of funds.

The Government reserves the right to award a task order without discussions if the Contracting Officer determines that the initial proposed cost/price is fair and reasonable and that discussions are not necessary.

If a proposal is not received on the date and time specified herein, it will be considered late and handled in accordance with subparagraph (c)(3) of FAR Clause 52.215-1, “Instructions to Offerors – Competitive Acquisition” and HHSAR Clause 352.215-70, “Late Proposals and Revisions”.

F. Offerors Questions: Questions regarding this TORFP #1 must be submitted to the Contracting Officer by 4:00 PM ET on 12/7/2020. Submit questions via email to the Contracting Officer, Ms. Alexis Hudak at alexis.hudak@nih.gov. Responses to questions will be emailed as an amendment to the TORFP.

mailto:alexis.hudak@nih.gov

Attachment 4- Task Order #1 Statement of Work (11/20/20)

G. Type of Task Order: Firm Fixed Price

H. Invoicing and Payment: See the base award for invoicing and payment instructions.

I. Anticipated Number of Task Order Awards: 3 (tentative)

J. Task Order Period of Performance: on or about 6/21/2021 - 7/20/2021

K. Technical Proposal Instructions: NONE

L. Business Proposal Instructions:

1. Business Proposal COVER SHEET: Submit the following:

• Solicitation or contract number

• Task order number

• Name and telephone number of point of contact

• Name, address, and telephone number of contract administration office (if applicable)

• Date of submission

• Name, title, and signature of authorized representative

2. Budget: Provide a summary of proposed cost and/or price (Attachment 1); profit or fee (as applicable); and total.

M. Evaluation Factors for Award:

1. Cost/Price: Offerors’ cost/price proposal will be evaluated for reasonableness. For a price to be reasonable, it must represent a price to the government that a prudent person would pay when consideration is given to prices in the market. Normally, price reasonableness is established through adequate price competition, but may also be determined through price analysis techniques as described in

FAR 15.404.

2. Understanding of the Requirement: Offer’s proposal will be evaluated for reasonableness of appropriate personnel and labor hours proposed.

N. Attachments

Attachment: Breakdown of Proposed Estimated Cost and labor hours (see Section J of the RFP).

Attachment 5 – Sample Task Order #2 (11/20/2020)

SAMPLE TASK ORDER #2

STATEMENT OF WORK

NOTE: THIS IS ONLY AN SAMPLE TASK ORDER REQUEST FOR PROPOSAL. WHILE A RESPONSE IS

REQUIRED AS PART OF YOUR SUBMISSION AS REFERENCED IN SECTION L OF THE RFP, NO

ACTUAL TASK ORDER AWARD WILL BE MADE IN RESPONSE TO THIS SAMPLE TASK ORDER.

TORFP No: _#2__

Order Title: Pharmacokinetic-Pharmacodynamic-Efficacy Evaluations with Selected Compounds in Human Tumor Xenografts in Nude Mice

Type of Order: Cost type task order

Period of Performance: Six months from date of award (estimated)

A. Statement of Work/Protocol/Project Description:

The purpose of this Task Order is to perform pharmacokinetic-pharmacodynamic-efficacy evaluation(s) with two investigational anticancer agents in a mouse tumor model (xenograft).

The contractor shall provide all necessary labor and materials to carry out the appended sample protocol entitled, “Pharmacokinetic-Pharmacodynamic-Efficacy Evaluation of [NSC XXX] in [cell line TBD] Tumor Xenografts in Nude Mice.” All collected samples are to be shipped to an NCI-designated laboratory for analysis.

B. Deliverables:

The following deliverables will be required.

1. A final protocol signed by the PII shall be provided to the COR prior to initiation of the study. A proposed study schedule shall be indicated on the cover page. Evidence of IACUC approval of the protocol shall also be provided.

2. Data Sheets: Data collected (animal weights, tumor weights, clinical observations, etc.) to be provided in Excel (or other agreed upon format) within 5 working days after the end of the in-life phase.

3. Samples Collected: Collected samples will be shipped to the protocol-designated laboratory.

Sample collection information and inventory/packing sheets to be provided with shipment and copied to the COR electronically.

4. Monthly Reports: Monthly Technical Progress Reports are required for this task order. These reports shall include: 1) a summary of progress on the study during the past month, 2) whether or not these projects are on schedule, and (3) whether any problems were encountered in the collection, handling or processing of data, including resolution of the problems.

The reporting period shall consist of each calendar month. The first report shall cover the period consisting of the first full calendar month following the effective date of the task order and any fractional part of the initial month. Reports shall be due on or before the 15th of each month following the end of each reporting period. A Monthly Study Progress Report shall not be submitted when the Final Report is due.

5. Draft and Final Reports: A narrative report shall include methods, in-life observations, and any problems or deviations encountered on the study. A draft report will be due 14 working days after the last sample is collected. The final report will be due 14 working days after return of the draft report for revision.

C. Evaluation Factors:

The evaluation criteria found in Section M of the ID/IQ RFP will govern the evaluation of responses received to this Sample Task Order Request for Proposals or TORFP (see Section M).

In an actual TORFP competed under any resultant IDIQ contract, study-specific evaluation criteria will be provided in this section.

D. Order Response Due Date: Responses to this Task Order shall be included in your technical and business proposals for this RFP.

E. Attachment: Protocol for Sample Task Order #2

SAMPLE PROTOCOL

TASK ORDER #2

Pharmacokinetic-Pharmacodynamic-Efficacy Evaluation of [NSCXXXXX] in [Cell Line TBD] Tumor Xenografts in Nude Mice

SPONSOR: Toxicology and Pharmacology Branch

Developmental Therapeutics Program Division of Cancer Treatment and Diagnosis National Cancer Institute National Institutes of Health Bethesda, Maryland 20892

MONITOR: TBD

CONTRACT NUMBER: TBD

CONTRACTOR: TBD

PRINCIPAL INVESTIGATOR: TBD

STUDY DIRECTOR: TBD

KEY DATES: I. OBJECTIVE

The objectives of this evaluation are to determine the efficacy of NSC(s) XXXXX against [cell line] xenografts in mice and to obtain plasma and tumor samples at various times to characterize the plasma and tumor pharmacokinetics and pharmacodynamics of the compound(s).

II. MATERIALS AND METHODS

A. Test Article and Vehicle:

1. Name of Test Article:

TBD

2. Vehicle:

TBD

3. Characterization and Documentation of Methods of Synthesis, Fabrication or Derivation or test article and vehicle:

a. Test Article:

Compound identity, strength, quality, stability and purity and documentation of methods of synthesis, fabrication or derivation are the responsibility of the NCI and will be communicated to the CRO.

b. Vehicle:

The vehicle (and its components) is stable throughout the date of expiration on the container labels when stored according to the manufacturer’s instructions.

B. Test System:

1. Species, Strain Supplier and Test System Justification:

Athymic nude (nu/nu NCr) mice obtained from an approved commercial supplier will be used in this evaluation.

2. Initial Age, Sex and Weight:

On the first day of dosing, the weight ranges of mice will be approximately 20-24 grams and the mice will be approximately 6 to 7 weeks of age. Only females will be used.

3. Care and Housing:

General procedures for animal care and housing will be in accordance with the Guide for the Care and Use of Laboratory Animals, National Research Council, 2011 and the U.S. Department of Agriculture through the Animal Welfare Act (Public Law 99-198). Appropriate caging and bedding or cage board (not cedar or pine chips) will be used. No contaminants should be present in the bedding that could interfere and affect the results of the evaluation. Environmental parameters will be set to maintain conditions specified in the facility SOPs. Environmental conditions will be within specified limits of at least 90 percent of scheduled observations.

4. Diet and Water Supply:

Diet shall consist of certified, commercial, dry rodent chow provided ad libitum.

Water source will be the public supply given ad libitum. No contaminants will be present in the feed or water that could interfere and affect the results of the evaluation.

5. Acclimation:

All animals will be isolated upon arrival, and the Attending Veterinarian or designee will document that the animals are healthy and free from disease and parasites.

The animals will be acclimated to the housing room for at least 5 days prior to dosing. Only healthy animals will be placed on test.

6. Animal Identification:

All mice will be given a unique identification number by ear punch or other approved method.

7. Human Tumor Xenograft:

Tumor cells will be obtained from the American Type Culture Collection (ATCC) or other approved source. Cells should be passaged in vitro according to the supplier’s recommendations. A suspension of [1x107] cells shall be implanted subcutaneously in sufficient host animals to conduct the evaluation described below. Tumors will be staged when the median tumor size reaches approximately 200 mg (or a designated size as per NCI direction).

C. Experimental Design

1. Randomization:

In order to obtain groups that are comparable by tumor weight, all mice will be randomly assigned to each treatment group using a computer-based body weight stratification procedure, randomizing for tumor volumes calculated as follows:

Tumor volume = 1/2(length × width2)

2. Group Assignments:

Upon randomization, 59 female mice will be assigned to the vehicle control group and 51 mice will be assigned to each of four treatment groups. Eight mice will be used as untreated controls.

Group # Mice Cpd. Route Dose (mg/kg) Conc. in

Formulation (mg/mL)

Dose Volume (mL/kg)

Schedule

1 59 (16 for efficacy) Vehicle IP 0 0 10 QD x 14

2 51 (8 for efficacy) NSC 1 IP Level 1 TBD 10 QD x 14

3 51 (8 for efficacy) NSC 1 IP Level 2 TBD 10 QD x 14

4 51 (8 for efficacy) NSC 2 IP Level 1 TBD 10 QD x 14

5 51 (8 for efficacy) NSC 2 IP Level 2 TBD 10 QD x 14

6 8 Untreated Controls -- -- -- -- --

3. Route of Administration and Reason for Choice:

The test compound will be given as daily intraperitoneal injections for 14 days in order to characterize the effects on tumor growth and the pharmacokinetic-pharmacodynamic time course in plasma and tumor.

4. Formulation Preparation

[Prepared twice-weekly; detailed procedures to be specified]

5. Dosing Procedure:

All mice in each group will receive either vehicle (Group 1) or formulated test article (Groups 2-5) by intraperitoneal injection on days 1 to 14. The dose volume will be 10 mL/kg of body weight for all dose groups. The amount of drug administered to each mouse will be based on each animal’s most recently determined individual body weight.

6. Measurements:

a. Clinical signs:

The mice will be observed at least once daily during the dosing period and at least twice weekly thereafter. Any adverse clinical signs will be recorded.

b. Body Weight:

Mice shall be weighed prior to dosing each day and the weight shall be used to adjust the dose volume for test article administration.

c. Tumor Volume:

Tumor volumes for all mice remaining on study will be measured by caliper at least twice weekly. Note that cohorts of 8 mice/group (16 in control group) will remain after the dosing/sampling period and should have tumor volume measurements at the above interval until the end of the evaluation (~50-60 days post-implant).

d. Plasma and Tumor Sample Collection:

Plasma and tumor samples will be collected as follows:

Day 1 Collections

Harvest tumors from 5 mice in Groups 1-5 at 2, 4, 8, 16, and 24 hr after dose 1 (the latter just prior to dose 2), cut into halves and flash freeze.

Collect blood in EDTA tubes at times of sacrifice - spin, flash freeze plasma.

Harvest tumor and plasma samples from all Group 6 (untreated) mice at a convenient time on Day 1

Day 4 Collections

Harvest tumors from 3 mice in Groups 1-5 at 2 hr after dose 4 and 24 hours (just prior to dose 5), cut into halves and flash freeze.

Collect blood in EDTA tubes at times of sacrifice - spin, flash freeze plasma.

Day 9 Collections

Harvest tumors from 3 mice in Groups 1-5 at 2 hr after dose 9 and 24 hours (just prior to dose 10), cut into halves and flash freeze.

Collect blood in EDTA tubes at times of sacrifice - spin, flash freeze plasma.

Day 14 Collections

Harvest tumors from 3 mice in Groups 1-5 at 2 hr and 24 hours after dose 14, cut into halves and flash freeze.

Collect blood in EDTA tubes at times of sacrifice - spin, flash freeze plasma.

Actual collection times will be recorded.

Blood samples will be placed on wet ice until centrifuged to obtain plasma.

Plasma samples will be transferred into appropriately labeled tubes and placed on dry ice until stored in a freezer set to maintain at least -70 ºC until all samples are ready for shipping.

Tumors will be excised from the implant site (according to facility SOP), cut into halves and flash frozen. Each tumor piece will be placed in a separate cryo vial and stored at least -70 ºC until all samples are ready for shipping.

d. Necropsy Procedure:

Necropsy is not required in this evaluation. Moribund animals and animals with excessive or necrotic tumor growth will be euthanized according to facility SOP.

e. Bioanalytical and Pharmacodynamic Analysis:

Plasma and tumor levels of the test article, as well as pharmacodynamic measurements will be conducted at another NCI-designated facility.

All samples from the evaluation should be shipped on dry ice in one batch to:

[To be specified in final protocol]

III. QUALITY ASSURANCE

A. Type of Evaluation This evaluation will not require compliance with the FDA Good Laboratory Practice Regulations.

B. Standard Operating Procedures

All operations pertaining to this evaluation, unless specifically defined in this protocol, will be performed according to the standard operating procedures of the laboratory and any deviations will be documented.

C. Protocol Amendments

All changes in or revisions of an approved protocol and the reasons therefore will be documented, signed, and dated by the Project Manager/Project Director and the NCI COR. Amendments will be maintained with the protocol. Verbal approval for minor modifications to the protocol (e.g., that do not impact cost/price, delivery schedule or other provisions) may be granted by the NCI COR, but a written amendment will follow. The Contractor shall promptly notify the Contracting Officer of any Government conduct that the Contractor regards as a change to the task order terms and conditions in accordance with FAR 52.243-7 “Notification of Changes”.

IV. REPORTING AND DISCUSSION OF DATA

B. Report and Data Analysis

6. Protocol: A fully signed protocol shall be provided to the COR prior to initiation of the evaluation, along with evidence of IACUC approval.

7. Data Sheets: Data collected (animal weights, tumor weights, clinical observations, etc.) to be provided in Excel (or other agreed upon format) within 5 working days after the end of the in-life phase.

8. Samples Collected: Collected samples will be shipped to the protocol-designated laboratory. Sample collection information and inventory/packing sheets to be provided with shipment and copied to the COR electronically.

9. Draft and Final Reports: Each report shall include methods, in-life observations, and any problems or deviations encountered. Draft reports will be due 14 working days after the last sample is collected. The final report will be due 14 working days after return of the draft report for revision.

V. REGULATORY REFERENCES

A. Facilities and Animal Husbandry:

Animal care will be in compliance with facility SOPs, the Guide for the Care and Use of Laboratory Animals, (Institute of Laboratory Animal Research, Division on Earth and Life Sciences, National Research Council; National Academy Press;

Washington, DC; 2011), and the U.S. Department of Agriculture through the Animal Welfare Act (Public Law 99-198).

B. Animal Welfare Act Compliance:

By signing this protocol, the Sponsor signifies that there are no generally accepted alternatives to the use of animals, and that the evaluation described by this protocol does not unnecessarily duplicate previously conducted or reported experiments.

Procedures used in this protocol are designed to conform to accepted practices and to minimize or avoid causing pain, distress, or discomfort in the animals. In those circumstances in which required test procedures are likely to cause more than momentary or slight pain or distress, the animals will receive appropriate analgesics or anesthetics unless the withholding of these agents has been justified in writing by the Project Director and approved by the facility’s Institutional Animal Care and Use Committee (IACUC).

C. Safety Compliance:

This evaluation will comply with all applicable federal and state regulations, including the CDC/NIH’s BMBL current edition, OSHA standard 1910.1450 “Occupational Exposure to Hazardous Chemical in Laboratories” and by applying recommended best practices or other recognized safe practices and codes. The evaluations will be conducted in a manner that ensures that the health, safety, and welfare of our employees, the public, and the environment are maintained.

Protocol Approvals:

Project Manager/Project Director:

TBD Date

NCI's Representative:

TBD Date

Attachment 6 – Sample Task Order #3 (11/20/2020)

SAMPLE TASK ORDER #3

NOTE: THIS IS ONLY AN SAMPLE TASK ORDER REQUEST FOR PROPOSAL. WHILE A RESPONSE IS REQUIRED AS PART OF YOUR SUBMISSION AS REFERENCED IN SECTION L OF THE RFP, NO ACTUAL

TASK ORDER AWARD WILL BE MADE IN RESPONSE TO THIS SAMPLE TASK ORDER.

TORFP No: _#3__

Order Title: Analytical Support for Pharmacology Evaluations of Selected Anticancer Agents_

Type of Order: Fixed-price type task order Period of Performance: One year from date of award

For the Base Task:

The contractor shall provide analytical support for the quantification of one small-molecule anticancer agent in plasma and tumor samples to be provided by NCI. These samples may be derived from efficacy or pharmacodynamic evaluations in mice or other pharmacology/toxicology evaluations to be specified. The in-life portion of all evaluations will be conducted at another NCI-designated facility.

Assume for costing purposes that a total 100 samples will be provided for quantification of a single analyte and that there will be no more than two matrices (e.g., plasma, tumor fragments).

The following specific efforts shall be carried out for the set of samples:

• Implement LC-MS/MS methodology for the quantification of the compound in plasma and tumor samples and perform limited validation as required. Assume a drug-like small molecule of ~300-700 MW. Full validation to GLP standard is not required.

• Determine levels of the compound in a total of 100 unknown samples to be provided to you by NCI. Run appropriate blanks, standards, and QC samples. Control matrix will be provided to the extent available.

• Non-compartmental PK parameters (Cmax, Tmax, AUC, t1/2) shall be calculated for plasma and tissues in each dose group (where allowed by the data available).

For Options 1 through 5:

For each Option exercised during the Period of Performance, the contractor shall analyze 100 additional plasma and/or tumor samples in the manner outlined above. The compounds to be determined may be different for the base period and each option. For each set of samples there will be no more than two matrices. Options are considered additional quantities, are not directly related to predetermined dates, and may be exercised at any time within the Task Order period of performance.

B. Deliverables:

Separately for the Base task and each Option exercised:

Attachment 6 – Sample Task Order #3 (11/20/2020)

• Preliminary Data File: Results of each study and data analysis performed (c vs. t data and derived PK parameters, with plots as appropriate) shall be provided to the COR in a tabular format (Excel) within two weeks of receipt of the samples to be analyzed.

• Final Data File: The Preliminary Data File shall be updated to include an outline of methods used (analytical conditions and validation, etc.), results of any sample or PK re-analysis, and any changes requested by the COR. All information should be formatted on separate tabs in Excel.

The Final Data File shall be due two weeks after receipt of comments on the Preliminary Data File.

• Monthly Reports: Monthly Technical Progress Reports are required for this task order. These reports shall include: 1) a summary of progress on the study during the past month, 2) whether or not the project is on schedule, and (3) whether any problems were encountered in the collection, handling or processing of data, including resolution of the problems.

The reporting period shall consist of each calendar month. The first report shall cover the period consisting of the first full calendar month following the effective date of the task order and any fractional part of the initial month. Reports shall be due on or before the 15th of each month following the end of each reporting period. A Monthly Study Progress Report shall not be submitted when the Final Report is due.

• A narrative final report (e.g., Word document) will NOT be required for this Task Order.

The evaluation criteria found in Section M of the ID/IQ RFP will govern the evaluation of responses received to this Sample Task Order Request for Proposals or TORFP (see Section M). In an actual TORFP competed under any resultant IDIQ contract, study-specific evaluation criteria will be provided in this section. Per the RFP, any options will be evaluated in accordance with FAR 52.217- 5.

D. Order Response Due Date: Responses to this Task Order shall be included in your technical and business proposals for this RFP.

Attachment 7 – Sample Task Order #4 (11/20/2020)

SAMPLE TASK ORDER #4

NOTE: THIS IS ONLY AN SAMPLE TASK ORDER REQUEST FOR PROPOSAL. WHILE A RESPONSE IS

REQUIRED AS PART OF YOUR SUBMISSION AS REFERENCED IN SECTION L OF THE RFP, NO

ACTUAL TASK ORDER AWARD WILL BE MADE IN RESPONSE TO THIS SAMPLE TASK ORDER.

TORFP No: _#4__

Order Title: Clinical Pharmacology Support for an NCI Phase I Trial of NSC XXXXX_

Type of Order: Fixed-price type task order

Period of Performance: Eighteen months from date of award (estimated)

The purpose of this Task Order (TO) is to provide a resource for analytical and pharmacokinetic support to an NCI Phase I clinical trial with NSC XXXXX:

Phase I Trial of NSC XXXXX in Adults with Refractory Solid Tumors

The following specific elements are included:

• Develop and validate to LC-MS/MS methodology for the quantification of NSC XXXXX in human plasma and urine. Full GLP not required, but validation should follow FDA guidance for clinical pharmacology assays.

• Secure all needed internal approval(s) for receipt and analysis of human samples to be generated by this NCI Phase I trial. The clinical protocol and certification of NIH IRB approval will be provided to the Contractor.

• Determine levels of NSC XXXXX in human plasma and urine samples obtained from up to

30 patients in the clinical trial. It is anticipated that 12 plasma and 3 urine samples will be collected from each patient in cycle 1 only (= 360 plasma samples and 90 urine samples).

Samples sets will be shipped as patients are accrued and treated, so planning for intermittent analyses will be critical. For costing purposes, assume samples will be analyzed in five (5) batches over the course Task Order period of performance.

• Pharmacokinetic data analysis shall include standard non-compartmental modeling to determine Cmax, Tmax, AUC0∞, AUClast, CL, and t½, Vss, for each patient. Cumulative urinary excretion and clearance shall also be determined. Compartmental and population modeling approaches may be also proposed.

B. Deliverables:

• Bioanalytical Validation Report. A narrative report documenting the proposed assay for

NSC XXXXX in plasma and urine shall be submitted to the COR before clinical sample

Attachment 7 – Sample Task Order #4 (11/20/2020) analysis begins. Suitability for intended use (accuracy, precision, reproducibility, specificity, etc.) statistics shall be tabulated consistent with FDA guidelines.

• Preliminary Data File. Interim c vs. t data and preliminary PK parameter estimates for each patient shall be tabulated in Excel and sent to the COR within 14 working days after receipt of samples.

• Final Data File: The Preliminary Data File shall be updated to include an outline of methods used (analytical conditions and validation, etc.), results of any sample or PK re-analysis, and any changes requested by the COR. All information should be formatted on separate tabs in Excel. The Final Data File shall be due two weeks after receipt of comments on the Preliminary Data File.

• Monthly Reports: Monthly Technical Progress Reports are required for this task order.

These reports shall include: 1) a summary of progress on the study during the past month,

2) whether or not the project is on schedule, and (3) whether any problems were encountered in the collection, handling or processing of data, including resolution of the problems.

The reporting period shall consist of each calendar month. The first report shall cover the period consisting of the first full calendar month following the effective date of the task order and any fractional part of the initial month. Reports shall be due on or before the 15th of each month following the end of each reporting period. A Monthly Study Progress Report shall not be submitted when the Final Report is due

• Draft Final and Final Reports: A draft clinical pharmacokinetics final report containing summary data, analysis, graphs, and conclusions across all patients in the trial will be due one month after completion of the final patient sample set. The final report will be due 14 working days after receipt of comments from the COR on the draft report.

C. Evaluation Factors

The evaluation criteria found in Section M of the ID/IQ RFP will govern the evaluation of responses received to this Sample Task Order Request for Proposals or TORFP (see Section M).

In an actual TORFP competed under any resultant IDIQ contract, study-specific evaluation criteria will be provided in this section.

D. Order Response Due Date: Responses to this Task Order shall be included in your technical and business proposals for this RFP.

Attachment 8 – Sample Task Order #5 (11/20/20)

SAMPLE TASK ORDER #5

NOTE: THIS IS ONLY AN SAMPLE TASK ORDER REQUEST FOR PROPOSAL. WHILE A RESPONSE IS REQUIRED AS PART OF YOUR SUBMISSION AS REFERENCED IN SECTION L OF THE RFP, NO ACTUAL

TASK ORDER AWARD WILL BE MADE IN RESPONSE TO THIS SAMPLE TASK ORDER.

TORFP No: _#5__

Order Title: Pharmacokinetics and Bioavailability Evaluations of Selected Anticancer Compounds in Mice

Type of Order: Fixed Price type task order Period of Performance: One year from date of award

The purpose of this Task Order is to characterize the plasma pharmacokinetics and bioavailability of candidate anticancer compounds in mice as outlined below.

For the base task:

1. Develop and/or adapt a standard LC-MS/MS bioanalytical approach for quantification of a small drug-like molecule in mouse plasma. A “generic” assay platform is acceptable and validation to full FDA bioanalytical guidance is not required. Potential internal standards will be provided if available. A lower limit of quantitation (LLOQ) of <5 ng/mL is desirable.

2. Carry out the appended protocol for mouse PK and bioavailability evaluations with one small-molecule, drug-like compound to be provided by NCI. Note for costing purposes that the protocol specifies 2 dose groups, two routes of administration, 8 time points, and 3 mice/time point, for a total of 48 plasma samples to be generated for analysis.

3. Pharmacokinetic data analysis should include standard non-compartmental modeling to determine Cmax(po), C0(iv), Tmax, AUC0∞, AUClast, CL, and t½, Vss, and %F for each compound.

For Options 1 - 5:

1. For each Option task exercised, the contractor shall perform PK-bioavailability evaluations as above and per the attached protocol for one additional small-molecule, drug-like compound per Option. Assume all compounds will be different. Minor adjustments to the protocol that should not affect cost or schedule (e.g., routes of administration, specific sampling times) may be made.

Options are considered additional quantities, are not directly related to predetermined dates, and may be exercised at any time within the Task Order period of performance.

B. Deliverables:

The following deliverables will be required for the base task and each option exercised:

1. A final protocol signed by the PII shall be provided to the COR prior to initiation of each PK study. A proposed study schedule should be indicated on the cover page. Evidence of IACUC approval of the protocol should also be provided.

2. Preliminary Data File: Results of each study and data analysis performed (c vs. t data and derived PK parameters, with plots as appropriate) shall be provided to the COR in an agreed upon tabular format (Excel) within two weeks of receipt of the finalization of the protocol.

3. Final Data File: The Preliminary Data File shall be updated to include an outline of methods used (analytical conditions and validation, formulation, etc.), results of any sample or PK re-analysis, and any changes requested by the COR. All information should be formatted on separate tabs in Excel. The Final Data File shall be due two weeks after receipt of comments on the Preliminary Data File.

4. Monthly Reports: Monthly Technical Progress Reports are required for this task order. These reports shall include: 1) a summary of progress on the study during the past month, 2) whether or not the project is on schedule, and (3) whether any problems were encountered in the collection, handling or processing of data, including resolution of the problems.

The reporting period shall consist of each calendar month. The first report shall cover the period consisting of the first full calendar month following the effective date of the task order and any fractional part of the initial month. Reports shall be due on or before the 15th of each month following the end of each reporting period. A Monthly Study Progress Report shall not be submitted when the Final Report is due.

5. A narrative final report (e.g., Word document) will NOT be required for this Task Order.

The evaluation criteria found in Section M of the ID/IQ RFP will govern the evaluation of responses received to this Sample Task Order Request for Proposals or TORFP (see Section M). In an actual TORFP competed under any resultant IDIQ contract, study-specific evaluation criteria will be provided in this section. Per the RFP, options will be evaluated in accordance with FAR 52.217-5.

D. Order Response Due Date: Responses to this Task Order shall be included in your technical and business proposals for this RFP.

E. Attachment- Protocol for Sample Task Order #5

SAMPLE PROTOCOL

TASK ORDER #5

PHARMACOKINETICS AND ORAL BIOAVAILABILITY OF NSC [TBD] IN MALE MICE

SPONSOR: Toxicology and Pharmacology Branch

Developmental Therapeutics Program

Division of Cancer Treatment and Diagnosis National Cancer Institute National Institutes of Health Bethesda, Maryland 20892

COR: TBD

CONTRACT NUMBER: TBD

CONTRACTOR: TBD

PRINCIPAL INVESTIGATOR: TBD

STUDY DIRECTOR: TBD

PROPOSED IN-LIFE PHASE:

Start: TBD

Finish: TBD

I. OBJECTIVE

The objective of this protocol is to characterize the plasma pharmacokinetics and oral bioavailability of NSC [TBD] in male mice.

II. MATERIALS AND METHODS

A. Test Article and Vehicle:

1. Name of Test Article:

NSC TBD (drug-like small molecule)

2. Name of Vehicle:

TBD in conjunction with the COR

3. Characterization and Documentation of Methods of Synthesis, Fabrication or Derivation:

a.