Strata PATH™ (Precision Indications for Approved Therapies)

Study Overview
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Brief Summary
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StrataPATH™ is a non-randomized, open-label trial designed to explore efficacy and safety of multiple FDA-approved and commercially available cancer therapies in new, biomarker-guided patient populations.

Detailed Description
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StrataPATH is a non-randomized, open-label trial designed to explore efficacy and safety of multiple FDA-approved and commercially available cancer therapies in new, biomarker-guided patient populations. Aiming to increase clinical benefit for patients, this study will leverage technology advancements, scientific literature, and Strata's real-world evidence to define novel, highly responsive pan-tumor molecular indications for FDA-approved therapies in both the advanced and micro-metastatic settings. Strata will rapidly identify participants who have efficacy signals for possible expansion into adaptive or randomized studies. Enrollment in each drug/biomarker cohort is competitive. Cohorts may be added, changed, or discontinued over the course of the study

Official Title
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Strata PATH™ (Precision Indications for Approved Therapies): A Study Evaluating the Clinical Activity and Safety of Approved Drugs Within Biomarker-Guided Patients With Solid Tumors

Conditions
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Cancer, Advanced Solid Tumor

Intervention / Treatment
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* Drug: lorlatinib
* Drug: encorafenib + binimetinib
* Drug: talazoparib
* Drug: fam-trastuzumab deruxtecan-nxki
* Drug: enfortumab vedotin
* Drug: sacituzumab govitecan
* Drug: pembrolizumab
* Drug: axitinib


Participation Criteria
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Eligibility Criteria
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To be eligible to participate in this study, an individual must meet each of the criterion below and the criteria indicated in the selected biomarker/drug cohort appendix: Male or female ≥18 years of age. Pathologically confirmed solid tumor Participants must be able to follow study visit schedule and willing to provide up to 20 mL of peripheral blood samples at the indicated time points CGP results need to be from a test conducted in a CLIA approved laboratory and archival formalin-fixed, paraffin-embedded (FFPE) tumor tissue is required for confirmatory testing of non-Strata test results unless otherwise indicated within the cohort-specific protocol criteria. Biomarker positive for the defined cohort For individuals with non-primary, treated or stable brain metastases: No evidence of progression (defined as no radiographic evidence of progression) for at least 4 weeks prior to consent. Adequate bone marrow, organ function & laboratory parameters as determined by the treating physician unless otherwise indicated within the cohort-specific protocol criteria. Adequate cardiac function: 1) Left ventricular ejection fraction (LVEF) ≥ 50% and 2) QTc interval ≤ 470 ms (females) or ≤ 450 ms (males) average preferred. An individual who meets any of the following criteria will be excluded from participation in this study: Receiving another cancer treatment Major surgery within 4 weeks prior to study entry Has received a systemic cancer treatment within 3 weeks of first study dose Individuals with a history of a second malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years or are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers that have been diagnosed and treated within the past 3 years are eligible: cervical/prostate carcinoma in situ, superficial bladder cancer, non-melanoma cancer of the skin. Patients with other cancers diagnosed within the past 3 years and felt to be at low risk of recurrence should be discussed with the study principal investigator to determine eligibility. Participant has primary central nervous system tumor. A woman of childbearing potential who has a positive urine pregnancy test (within 72 hours) prior to treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Females who are pregnant or nursing or plan to become pregnant or anyone unwilling to use contraception for the duration of treatment. Ongoing toxicity of CTCAE grade >2, other than peripheral neuropathy, related to anticancer therapy that was completed within 4 weeks of consent. Ongoing peripheral neuropathy of CTCAE grade >3. History of stroke including transient ischemic attack (TIA) or acute myocardial infarction within 6 months of consent. Participant has a known history of human immunodeficiency virus (HIV), Hepatitis B or known active Hepatitis C virus infection. Medical condition that would place the patient at risk as a result of blood donation, such as bleeding disorder. Any other clinically significant medical condition that, in the opinion of the treating physician, makes participation undesirable, including but not limited to ongoing or active infection, significant uncontrolled hypertension, or severe psychiatric illness.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Lorbrena® (lorlatinib)<br> | Drug: lorlatinib<br>* This arm of the Strata PATH trial will assess the clinical benefit of Lorbrena® (lorlatinib) in ALK and ROS1 gene fusion positive solid tumors, as detected by Strata testing, with the exception of NSCLC.<br>|
| Other: Braftovi® (encorafenib) + Mektovi® (binimetinib)<br> | Drug: encorafenib + binimetinib<br>* This arm of the Strata PATH trial will assess the clinical benefit of Braftovi® (encorafenib) + Mektovi® (binimetinib) in BRAF p.v600X mutated solid tumors, as detected by Strata testing, with the exception of melanoma and colorectal cancer.<br>|
| Other: Talzenna® (talazoparib)<br> | Drug: talazoparib<br>* This arm of the Strata PATH trial will assess the clinical benefit of Talzenna® (talazoparib) in patients with advanced solid tumors harboring deep deletions or deleterious mutations with LOH in BRCA1/2 and PALB2, as detected by Strata testing, excluding HER2 negative breast cancer.<br>|
| Other: Enhertu® (fam-trastuzumab deruxtecan-nxki)<br> | Drug: fam-trastuzumab deruxtecan-nxki<br>* This arm of the Strata PATH trial will assess the clinical benefit of Enhertu® (fam-trastuzumab deruxtecan-nxki) in patients with advanced solid tumors harboring HER2 over-expression, as detected by Strata testing (HER2 Expression Score positive [HER2 ES-positive]), excluding breast cancer, gastric cancer, or gastroesophageal junction (GEJ) cancer.<br>|
| Other: Padcev® (enfortumab-vedotin)<br> | Drug: enfortumab vedotin<br>* This arm of the Strata PATH trial will assess the clinical benefit of Padcev® (enfortumab-vedotin) in patients with advanced solid tumors and are Nectin-4 Expression Score High (Nectin-4 ES-H), as detected by Strata testing, excluding urothelial cancer.<br>|
| Other: Trodelvy® (sacituzumab govitecan-hziy)<br> | Drug: sacituzumab govitecan<br>* This arm of the Strata PATH trial will assess the clinical benefit of Trodelvy® (sacituzumab govitecan) in patients with advanced solid tumors and are Trop2 Treatment Response Score High (Trop2 TRS-H), as detected by Strata testing, excluding triple negative breast cancer, hormone receptor positive/ human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer, metastatic urothelial cancer, non-small cell lung (NSCLC) cancer, small cell lung cancer (SCLC), head and neck cancer, colorectal cancer (CRC), and endometrial cancer.<br>|
| Other: Keytruda® (pembrolizumab)<br> | Drug: pembrolizumab<br>* This arm of the Strata PATH trial will assess the clinical benefit of pembrolizumab in patients with advanced solid tumors and are Immunotherapy Response Score High (IRS-H), as detected by Strata testing, excluding approved pembrolizumab indications.<br>|
| Other: Inlyta® (axitinib)<br> | Drug: axitinib<br>* This arm of the Strata PATH trial will assess the clinical benefit of Inlyta® (axitinib) in patients with advanced solid tumors and are Angiogensis Inhibitor Treatment Response Score High (Angio TRS-H), as detected by Strata testing, excluding renal cell carcinoma, alveolar soft part sarcoma, and solitary fibrous tumors.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) defined as the percentage of participants with a best overall response of CR or PR based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, as assessed by the investigator | RECIST criteria will be used to assess the clinical activity of cancer treatments in participants with pre-specified biomarker profiles. | Assessed throughout end of study, up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DoR) defined as the time from first documentation of disease response (CR or PR) until first documentation of progressive disease | DoR will be used to assess the duration of response of cancer treatments in participants with pre-specified biomarker profiles. | Assessed throughout end of study, up to 5 years | 
| Time to Treatment Discontinuation (TTD) defined as length of time from the date the participant initiates the systemic treatment to the date the participant discontinues treatment as compared to prior TTD from prior cancer treatment | TTD will be used to assess the duration of response of cancer treatments in participants with pre-specified biomarker profiles. | Assessed throughout end of study, up to 5 years | 
| TTnT (Time to Next Treatment) defined as the length of time from the date the participant initiates study treatment to the date the participant initiates their next systemic treatment or death. | TTnT will be used to assess the duration of response of cancer treatments in participants with pre-specified biomarker profiles. | Assessed throughout end of study, up to 5 years | 
| ctDNA response: The proportion of participants with a <50% ratio of mean variant allele frequency (VAF) will be defined as ctDNA responders | Molecular response calculated as a ratio of mean VAF on treatment at 6 months compared to baseline VAF will be used to assess the clinical activity of cancer treatments in participants with pre-specified biomarker profiles. | 6 months | 
| Overall Survival (OS) | Evaluate overall survival (OS) for participants who received a cancer treatment with pre-specified biomarker profiles | Assessed throughout end of study, up to 5 years | 
| Incidence of serious adverse events (SAEs) | Monitor and summarize any unexpected safety events in participants who received a biomarker-guided cancer treatment | Assessed throughout end of study, up to 5 years | 
| ctDNA Response Rate | Evaluate ctDNA response rate at additional timepoints for participants who received cancer treatment with pre-specified biomarker profiles | Assessed throughout end of study, up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Advanced Solid Tumor