Influencing Next-Generation Oncologic Outcomes Through Rapid Integration of Functional Precision Medicine (NOORI): A Feasibility Study of SmartMatch in Rare Gynecologic Cancers

OUTLINE: This is an observational study.

Patients undergo tissue sample collection obtained from standard of care surgical resection or biopsy for SmartMatch laboratory analysis and have their medical records reviewed on study.

Primary outcomes

• Proportion of participants for whom SmartMatch generates at least one actionable treatment recommendation that is presented at the PMTB within 4 weeks (≤ 28 days) of fresh tissue acquisition [From enrollment up to 36 months]: An actionable recommendation is defined as: 1. FDA-approved therapy for any indication or available clinical trial; 2. Predicted to have activity by SmartMatch functional precision medicine (FPM) and/or genomics; 3. Endorsed by PMTB as clinically reasonable.

Secondary outcomes

• Implementation Feasibility: Proportion of PMTB-recommended therapies successfully obtained [Up to 36 months]
• Implementation Feasibility: Time from PMTB recommendation to first dose of matched therapy [Up to 36 months]
• Implementation Feasibility: Time from live tissue collection to SmartMatch report [Up to 36 months]
• Implementation Feasibility: Reasons for access failure/delay (insurance denial, clinical decline, etc.) [Up to 36 months]: Will document reasons for failure or delay (insurance denial, lack of trial access, toxicity concerns, clinical deterioration, patient preference)
• Proportion of patients achieving growth modulation index (GMI) ≥ 1.3 [Up to 36 months]
• Proportion of patients achieving progression-free survival on matched therapy (PFSmatched) [Up to 36 months]
• Proportion of patients achieving progression-free survival on the prior line of therapy (PFSpast) [Up to 36 months]
• Proportion of patients achieving GMI = PFSmatched / PFSpast [Up to 36 months]
• Proportion of patients who begin identified treatment pathways following Precision Medicine Tumor Board (PMTB) review [Up to 36 months]: Proportion of patients falling into each pathway: * Genomic-matched therapy implemented * Functional/organoid-matched therapy implemented * Physician's choice therapy (no matched therapy recommended, not obtainable, or declined)

Sex: Female, ages: 18 Years to any

Inclusion Criteria:

* Age ≥ 18 years
* Histologically confirmed rare gynecologic malignancy, including but not limited to those listed
* Metastatic or unresectable disease, OR disease for which additional systemic therapy is indicated
* Fresh tumor tissue available from a SOC surgical procedure or biopsy that in the judgment of the treating team will yield adequate viable tumor for SmartMatch analysis
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Adequate organ function to receive systemic therapy as determined by the treating oncologist (protocol does not specify thresholds because therapy is not mandated)
* Ability to understand and willingness to sign informed consent
* Willingness to allow data abstraction from the electronic health record for study endpoints

Exclusion Criteria:

* Lack of tumor tissue suitable for SmartMatch analysis
* Purely borderline tumors or benign ovarian/uterine neoplasms
* Any condition that, in the opinion of the treating oncologist or PI, would interfere with receiving systemic therapy
* Inability to provide informed consent or comply with study procedures

• Kalyan Banda, MD, Principal investigator, Fred Hutch/University of Washington Cancer Consortium