Draft_SOW.pdf

STATEMENT OF WORK (SOW)

1.0 TITLE

Multi‐omic Analyses for the Comprehensive Interrogation of Tumors with the SMART System

2.0 BACKGROUND

The Metastasis Biology Section of the Surgical Oncology Program (SOP) of the at the National Cancer Institute, National Institutes of Health, seeks to interrogate the molecular underpinnings of metastatic solid tumor biology. Some cancers are resistant to current treatments, and many individuals fail to respond to therapies that are highly beneficial to others with the same diagnosis. In particular the spatial organization of cells in the tumor microenvironment is central to understanding determinants of response. Complicating the translational applicability of potential tumor models has been inter‐tumoral heterogeneity. It is well established that patients with solid tumors succumb from metastatic disease, which can differ substantially from the primary tumor in terms of composition.

Currently, there is no tumor model that accurately and faithfully recapitulates the heterogeneity of the human tumor microenvironment inclusive of 3D structure, stromal components, and immune populations. The Government circumvented this shortcoming by generating an ex vivo model directly from patient derived metastasis‐bearing tissue and, by means of prolonged ex vivo animation, to produce a powerful platform for therapeutic testing. To date, the Surgical Oncology Program has engineered a comprehensive translational platform capable of achieving this goal, termed the SMART (Surgically‐resected Mesothelium containing Unaltered Tumor Microenvironment) System. This platform utilizes thin sections of human tissue containing macroscopically apparent tumor that are affixed to small platforms and placed into a chamber integrated into a perfusion circuit. The setup has been designed to continuously expose the tissue to well oxygenated autologous perfusate made from the patient’s own plasma. This allows for the maintenance of physiologic conditions and monitoring a myriad of metabolic parameters. The system was designed with the ease of adding experimental agents and sampling of both the tissue and the perfusate in mind, which ensures minimal disruption of the tissue environment. Furthermore, this system provides the ability to observe the tumor ex vivo via live multiplex imaging. Utilizing a patented imaging adaptor, the tumor microenvironment can be interrogated, giving special consideration to the interaction of tumor cells with various immune cells in real‐time, with and with the addition of oncology agents.

The Government has already begun to exploit the SMART system with the targeting of a cytosolic complex between Exportin‐7 (XPO7) and Ste20‐like kinase (SLK), which were discovered by the SOP in cholangiocarcinoma (CCA) and have subsequently expanded to ovarian carcinoma (OC). Most translational efforts for uncommon diseases stem from next generation sequencing approach that identify and target specific mutations, or general attempts to alter/augment the immune system. The SOP used 318 patient samples to demonstrate specific cytoplasmic accumulation of XPO7 within tumor cells in a subset of patients with CCA and OC and further verified this localization pattern in cell lines.

The SOP then used the cells lines to show that XPO7 binds to and stabilizes Ste20‐like kinase (SLK), which in turn activates downstream oncogenic signaling pathways. Given the absence of specific SLK inhibitors, the SOP next profiled the kinome‐specificity of 250 inhibitors to identify those with activity against SLK.

Using murine xenografts, a GEMM (TgK18GT121tg/+/p53fl/fl/Brca1fl/fl) and tumors from patients in the SMART system, the SOP demonstrated that tivozanib treatment resulted in tumor shrinkage/tumor cell killing and substantial morphologic alterations similar to those observed with XPO7 or SLK knockdown.

Based upon these results, the Government opened a Phase I/II trial (NCT 04645160) for patients with CCA and expect to achieve high response rates in a heavily pre‐treated population. However, tumor cells lacking demonstrable staining. Not surprisingly, cures have not been reported with single agent tivozanib treatment despite impressive responses in some patients. Therefore, combination therapies pursue a multi‐faceted approach including comprehensive interrogation using the SMART system.

2.1 OBJECTIVE

The Government will share de‐identified clinical information (overall survival or recurrence‐free survival, treatment, and response, SMART system outcomes) with the contractor. These clinical information data sets will encompass an estimated 18‐24 patients annually (not all data may be delivered for each patient). These data will guide the application of oncology agents and a great appreciation of tumor heterogeneity is required.

3.0 SCOPE

The scope of work will cover bio‐informatic analysis for data generated by SOP’s ex vivo human tumor systems. Integrated analyses shall be performed across all clinical information datasets and with clinical outcome and SMART system results. The contractor shall share all generated bioinformatic data with the Government.

4.0 CONTRACT REQUIREMENTS

Independently and not as an agent of the Government, the contractor shall provide all labor, materials, equipment, and personnel to accomplish the following Task:

4.1 TASK #1 – Initial Management Meeting

Within three (3) days of contract award, the Contractor shall provide the NCI’s TPOC and COR with information regarding the Contractors’ Primary Point of Contact for all services to be provided in relation to this award. This will include a meeting to discuss and plan upcoming analysis to be performed, as well as initial annual forecasting.

4.2 TASK #2 – Multi‐omic Analyses Analysis of Clinical Information

The Contractor shall perform analysis of data generated and provided by the Government as requested.

Data analysis shall include the following for all data sets provided.

1) Conduct generated datasets as requested:

a. Whole genome sequence (WES) analysis;

b. RNA sequence (RNAseq) analysis;

c. Small circular RNA (scRNA‐seq) analysis.

Results shall include mutation calling, gene expression level, tumor cellular composition, activity of tumor‐promoting and inhibiting processes. The generated molecular profiles will be correlated with clinical outcome and integrated with the other analyses.

2) Perform analysis of already imaged datasets:

a. Generation of cell‐segmentation masks;

b. Extraction of single‐cell features to individual FCS (Flow Cytometry Standard) files corresponding to each ROI;

c. Cell phenotype clustering and annotation of FCS files;

d. Generation of t‐SNE (t‐distributed Stochastic Neighbor Embedding) plots, annotated for cell phenotype clusters, per region and combined;

e. Generation of metrics describing the frequency of different immune cell phenotypes, per region and combined;

f. Generation of cellular contact analysis, per region and combined;

g. Cell proximity analysis (communities), per region and combined.

3) Perform flow cytometry analyses for cell population detection.

4) Perform proteomics analyses, to include:

a. Correlation with gene expression;

b. Comprehensive pathway analysis;

c. Integrative pathway analysis;

d. Neoantigen analysis.

5) Conduct perfusate analysis, which shall include ELISA.

6) Perform integrated analyses across all datasets and with clinical outcomes and SMART system results.

Immediately upon completion, all information will be sent directly to the government’s Technical Point of Contact.

4.3 TASK #3 – Annual Report

One (1) week prior to the expiration of the award, the Contractor shall provide the TPOC and COR with a report summarizing work completed in support of NCI. This shall include the number of analyses conducted, as well as the average time required for each analysis to be performed.

5.0 GOVERNMENT FURNISHED INFORMATION

The Government will furnish the clinical data sets to the contractor for analysis within (3) days of identified need. All data shared, or otherwise generated throughout the duration of this Purchase Order shall remain or become the sole property of the U.S. Government.

6.0 PLACE OF PERFORMANCE

All Services shall be performed at the Contractor’s facilities.

7.0 PERIOD OF PERFORMANCE:

The estimated Period of Performance shall be for one (1) twelve (12) month base period, with one (1) twelve (12) month Option Period as follows:

Base: 9/25/2022 – 9/24/2023 Option Period: 9/25/2023 – 9/24/2024

8.0 TYPE OF ORDER

This is a severable Firm‐Fixed‐Unit‐Price Purchase Order. The services acquired under this contract are severable services. Funds are only available for use for the contract line item (CLIN) to which they are obligated. Unused funds from one CLIN may not rollover for use in other periods.

8.1 CEILING PRICE

(a) The parties estimate that performance of this contract will not cost the Government more than the Ceiling Price specified in the Price Schedule.

(b) The Government is not obligated to reimburse the Contractor for costs incurred in excess of the Ceiling Price; and the Contractor is not obligated to continue performance under this contract in excess of the Ceiling Price specified in the Price Schedule, until the Contracting Officer (i) notifies the Contractor in writing that the Ceiling Price has been increased and (ii) provides a revised Ceiling Price of performing this contract.

(c) No notice, communication, or representation in any form other than that specified in paragraph (b) of this clause, or from any person other than the Contracting Officer, shall affect this contract’s Ceiling Price to the Government. In the absence of the specified notice, the Government is not obligated to reimburse the Contractor for any costs in excess of the Ceiling Price.

(d) Change Orders/Modifications shall not be considered an authorization by the Government to exceed the Ceiling Price specified in the Price Schedule unless the action explicitly contains a statement increasing the Ceiling Price.

(e) Funds remaining following receipt of the Final Invoice may be unilaterally de‐obligated by the Government.

(f) This contract is divisible. In the case of default, the Contractor shall be paid for units delivered and accepted. The Contractor’s responsibility for default shall only be with respect to uncompleted work.

9.0 PRICE SCHEDULE

The following price schedule is for estimated quantities to establish the price per imaging analysis of clinical datasets and the overall Ceiling Price for line items. Actual quantities purchased may vary.

10.1 Base Period

Item

Item Description Estimated Quantity

Price Per Data Analysis

Estimated Total

Ceiling Price

1 Imaging Analysis of clinical data sets to include:

NGS Analysis

Flow Cytometry Analysis

Proteomics Analysis

Perfusate Analysis

Ceiling Price:

10.3 Option Period 1

Item

Item Description Estimated Quantity

Price Per Data Analysis

Estimated Total

Ceiling Price

1 Imaging Analysis of clinical data sets to include:

NGS Analysis

Flow Cytometry Analysis

Proteomics Analysis

Perfusate Analysis

Ceiling Price:

* Estimated Quantities are provided to establish the Price Per unit and overall ceiling price for line items.

Actual quantities of analysis may vary.

9.1.1 Delivery report shall be sent to the COR and Technical Point of Contact (TPOC) indicating the number of analyses furnished.

9.1.2 A final report shall be sent to the COR and TPOC indicating the number of awards furnished throughout the period of performance and broken down by award type

10.0 REPORT(S)/DELIVERABLES AND DELIVERY SCHEDULE

DELIVERABLE

DELIVERABLE DESCRIPTION / FORMAT

REQUIREMENTS

DUE DATE

Task #1 Project Management Plan in Word or PDF format Three (3) Days

Task #2 Data Analysis of Clinical Information Immediately Upon Completetion

Task #3 Annual Report One (1) Week Prior to Award Expiration.

11.0 INSPECTION AND ACCEPTANCE

Pursuant to FAR clause 52.212‐4, all work described in the SOW is to be delivered under this purchase order is subject to final inspection and acceptance by an authorized representative of the Government.

The authorized representative of the Government is the TPOC who is responsible for inspection and acceptance of all services, materials, or supplies to be provided by the Contractor.

Regardless of format, all digital content or communications materials produced as a deliverable under this contract, shall conform to applicable Section 508 Standards to allow Federal employees and members of the public with disabilities to have access to and use of information and data that is comparable to the access to and use of information and data by Federal employees or by members of the public who are not individuals with disabilities. Remediation of any materials that do not comply with the applicable Section 508 requirements as set forth below, shall be the responsibility of the Contractor.

HHS guidance regarding accessibility of documents can be found at:

https://www.hhs.gov/web/section‐508/making‐files‐accessible/create‐accessible‐pdfs/index.html.

Federal government‐wide guidance regarding accessibility of documents can be found at https://www.section508.gov/, including the documents describing the preferred method of authoring and testing documents produced in Microsoft Word 2013 or later, Microsoft Excel, and files formatted as PDF.

All written deliverable products shall be submitted in draft format for review, comment, and approval by the TPOC. Final copies of approved drafts shall be delivered to the COR/TPOC within three (3) business days after receipt of the Government’s comments.

All written draft and final deliverable products shall be submitted in electronic copy for review and comment. If requested, final deliverable products shall be submitted in an electronic format. Other quantities and formats may be submitted after prior approval from the COR/TPOC.

All deliverables shall be sent electronically (Microsoft Excel 2013, Microsoft Excel, or Adobe Portable Document Format (PFD), unless otherwise approved by the COR/TPOC) per the following deliverable schedule contained in Section 9.0 below.

12.0 CONTRACTING OFFICERS REPRESENATIVE (COR)

The following Contracting Officer Representative (COR) will represent the Government for the purpose of this Purchase Order:

TBD AT AWARD

The Following Individual shall be the Technical Point of Contact for this Purchase Order:

TBD AT AWARD

The COR is responsible for:

1. Monitoring the Contractor's technical progress, including the surveillance and assessment of performance and recommending to the Contracting Officer changes in requirements;

2. Interpreting the statement of work and any other technical performance requirements;

3. Performing technical evaluations as required;

4. Performing technical inspections and acceptances required by this contract; and

5. Assisting in the resolution of technical problems encountered during performance.

The COR does not have the authority to issues technical directions that:

1. Constitutes a change of assignment or additional work outside the Statement of Work (SOW);

2. Constitutes a change as defined in the clause 52.212‐4 (c)";

3. In any manner causes an increase or decrease in the contract price, or the time required for contract performance;

4. Changes any of the terms, conditions, or requirements of the contract;

5. Interferes with the Contractor's right to perform under the terms and conditions of the contract;

or

6. Directs, supervises, or otherwise controls the actions of the Contractor's employees.

The alternate TPOC is responsible for carrying out the duties of the COR only in the event that the COR is not available or can no longer perform his/her duties as assigned.

The Contracting Officer is the only person with authority to act as agent of the Government under this Purchase Order. Only the Contracting Officer has authority to:

1. Direct or negotiate any changes in the statement of work;

2. Modify or extend the period of performance;

3. Change the delivery schedule;

4. Authorize reimbursement to the Contractor for any costs incurred during the performance of this contract;

5. Otherwise change any terms and conditions of this contract; or

6. Unilaterally change the Governments COR.

13.0 PAYMENT

Payment shall be made in arrears after performance of service is confirmed through the monthly reports submitted to the COR as described in section 9.0 above. Payment authorization requires submission and approval of invoices to the COR, Purchasing Agent (PA) and NIH OFM, in accordance with the attached payment provisions.