PRO1184 for Advanced Solid Tumors

Study Overview
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Brief Summary
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This study will test the safety, including side effects, and determine the characteristics of a drug called PRO1184 in participants with solid tumors. Participants will have solid tumor cancer that has spread through the body (metastatic) or cannot be removed with surgery (unresectable). This study will have two parts. Part A of the study will find out how much and how frequently PRO1184 should be given to participants. Part B will use the dose and schedule found in Part A to find out how safe PRO1184 is and if it works to treat solid tumor cancers.

Detailed Description
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This is a Phase 1/2 study of PRO1184, a folate receptor alpha (FRα) targeted antibody-drug conjugate, to evaluate the safety, tolerability, PK, and antitumor activity of PRO1184 in patients with selected locally advanced and/or metastatic solid tumors, including epithelial ovarian cancer, endometrial cancer, breast cancer, non-small cell lung cancer, and mesothelioma. This study consists of 2 parts, Part A: Dose Escalation and Part B: Dose Expansion. Part A may evaluate up to 7 dose levels of PRO1184 on Day 1 of a 21 day cycle by IV infusion. Part B will be initiated at a dose level based on a comprehensive analysis of safety, tolerability, clinical PK, PD and activity data from Part A in up to 4 different cohorts of up to 20 patients per cohort. Patients will continue to receive study treatment until the first instance of disease progression, unacceptable toxicity, investigator decision, consent withdrawal, study termination by the Sponsor, pregnancy, or death.

Official Title
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Phase 1/2 Study of PRO1184 in Patients With Locally Advanced and/or Metastatic Solid Tumors

Conditions
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Ovarian Cancer, Primary Peritoneal Carcinoma, Fallopian Tube Cancer, Endometrial Cancer, Non-small Cell Lung Cancer, Mesothelioma, Triple Negative Breast Cancer, HER2-negative Breast Cancer, Hormone Receptor-positive Breast Cancer

Intervention / Treatment
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* Drug: PRO1184


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histologically or cytologically confirmed metastatic or unresectable solid malignancy including ovarian cancer (must have epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer), endometrial cancer, non-small cell lung cancer, breast cancer (hormone receptor positive, HER2-negative and triple-negative), mesothelioma previously received therapies known to confer clinical benefit willing to provide a tumor sample (archive tissue or fresh biopsy) ECOG performance status 0 or 1 measurable disease per RECIST v1.1 for all tumor types other than pleural mesothelioma which will use mRECIST v1.1 at baseline adequate hematologic, hepatic, renal and cardiac function for Part B, evidence of folate receptor alpha expression in tumor cells Exclusion Criteria: other malignancy within 3 years active CNS metastases (treated, stable CNS metastases are allowed) uncontrolled Grade 3 or greater infection within 2 weeks positive for HBV, HCV or HIV use of a strong P450 CYP3A inhibitor within 14 days (dose escalation only) additional protocol defined inclusion/exclusion criteria may apply

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
Intervention Model: Single Group Assignment
Interventional Model Description: Patients will receive PRO1184 in ascending dose levels to establish a maximum tolerated dose, if reached, and the recommended Phase 2 dose, followed by dose expansion at selected dose and schedule.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRO1184<br>PRO1184 monotherapy in escalating doses in Part A and at the recommended dose in Part B. | Drug: PRO1184<br>* Intravenous infusion of PRO1184<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Type, incidence, severity, and seriousness of adverse events | Through end of treatment, up to approximately 1 year. | 
| Dose limiting toxicity | The proportion of patients experiencing dose limiting toxicities | At the end of Cycle 1 (each cycle is 21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response | Best response per RECIST v1.1 criteria for all tumor types other than pleural mesothelioma which will use mRECIST v1.1 | Up to approximately 1 year. | 
| Objective response rate | Patients who achieve partial or complete response per RECIST v1.1 criteria | Up to approximately 1 year. | 
| Disease control rate | Patients who achieve stable disease, partial or complete response per RECIST v1.1 criteria | Up to approximately 1 year. | 
| Progression-free survival | Time from start of treatment to first documented disease progression or death | Up to approximately 18 months. | 
| Overall survival | Time from the start of study treatment to the date of death from any cause | Up to approximately 2 years. | 
| Duration of objective response | Time from the first documentation of an objective tumor response (CR or PR) to the first documented tumor progression or death | From date of enrollment until the date of first documented disease progression or date of study withdrawal, whichever came first, assessed up to 12 months. | 
| Peak Plasma Concentration (Cmax) for PRO1184 | Measurement of maximum plasma concentration after the administration of PRO1184. | Through end of treatment, up to approximately 1 year. | 
| Area under the plasma concentration versus time curve (AUC) for PRO1184 | Measurement of AUC after the administration of PRO1184. | Through end of treatment, up to approximately 1 year. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antibody-drug conjugate, folate receptor alpha, folate receptor, solid tumor, ovarian cancer, primary peritoneal carcinoma, fallopian tube cancer, endometrial cancer, non-small cell lung cancer, mesothelioma, breast cancer, triple negative breast cancer, HR+/HER2- breast cancer, topoisomerase I inhibitor, phase 1, ProfoundBio