PRO1184 for Advanced Solid Tumors

Phase 1

Recruiting

• Conditions: Endometrial Cancer; Non-small Cell Lung Cancer; High Grade Epithelial Ovarian Cancer; Triple Negative Breast Cancer; Primary Peritoneal Carcinoma; Fallopian Tube Cancer; Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer (NSCLC); Mesothelioma; Breast Adenocarcinoma; Platinum Sensitive Ovarian Cancer (PSOC)
• Interventions: Drug: PRO1184; Drug: PRO1184 intravenous infusion of PRO1184

• Registration Number: NCT05579366
• Lead Sponsor: ProfoundBio US Co.

Brief Summary

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).

Detailed Description

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 participants with selected locally advanced and/or metastatic solid tumors, including epithelial ovarian cancer, endometrial cancer, breast cancer, non-small cell lung cancer, and mesothelioma.

The study consists of 4 main parts:

Part A: dose-escalation cohorts

Part B: tumor-specific monotherapy dose-expansion cohorts

Part C: platinum-resistant ovarian cancer (PROC) cohort

Part D: combination therapy cohorts

Participants 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.

Study Timeline

• Study First Submitted: 2022-10-04
• Study First Submitted QC: 2022-10-11
• Study First Posted: 2022-10-13
• Study Start: 2022-12-07
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-04
• Last Update Posted: 2024-11-05
• Primary Completion: 2025-10
• Study Completion: 2026-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 354

Inclusion Criteria

Part A and B:

• 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 (Part A), EGFR-mutated NSCLC (Part B), breast cancer (hormone receptor positive, HER2-negative and triple-negative) (Part A), mesothelioma.
• Previously received therapies known to confer clinical benefit.
• Willing to provide a tumor sample (archive tissue or fresh biopsy).
• Eastern cooperative oncology group (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.

Part C:

High grade serous ovarian cancer, primary peritoneal cancer, or fallopian tube cancer (excluding endometrioid, clear cell carcinomas, mucinous, low grade, and those with a sarcomatous or neuroendocrine element)

• Participants must have received 1 to 3 lines of therapy.
• Participants must have platinum-resistant/refractory ovarian cancer.
• Participants must have received prior bevacizumab.
• Participants with known or suspected deleterious germline or somatic BRCA mutations (as determined by FDA-approved test in a CLIA-certified laboratory) must have been treated with a poly ADP-ribose polymerase (PARP) inhibitor.
• Participants must have known FRα status based on an FDA approved test (the Ventana FOLR1 RxDx Assay). Those who are FRα positive must have previously received mirvetuximab soravtansine, (MIRV), unless the patient has a documented medical exception.
• Prior induction plus maintenance is considered 1 line of therapy, even if parts of the treatment regimen (induction or maintenance) are interrupted and/or resumed at a later date, in the absence of disease progression while on active treatment.
• A switch/change in regimen due solely to toxicity or participant preference (and not disease progression) is not considered a separate line of therapy.

Part D:

Cohort D1 (PRO1184+carboplatin):

• Participants must have platinum-sensitive ovarian cancer.
• Participants must have received 1 to 3 prior lines of therapy.

Cohort D2 (PRO1184+bevacizumab):

• Participants must have platinum-resistant/refractory ovarian cancer.
• Patients must have received 1 to 2 prior lines of therapy.

Cohort D3 (PRO1184+pembrolizumab):

• Endometrial cancer (any subtype excluding sarcoma).
• Participants must have received prior platinum-based chemotherapy for recurrent or advanced disease.

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Exclusion Criteria

• Other malignancy within 3 years.
• Active central nervous system (CNS) metastases (treated, stable CNS metastases are allowed).
• Uncontrolled Grade 3 or greater infection within 2 weeks.
• Positive for HBV, HCV or human immunodeficiency virus (HIV).
• History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids within the past 2 years, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
• Use of a strong CYP3A inhibitor within 14 days (dose escalation only).
• Prior therapy with a topoisomerase 1 inhibitor-based antibody drug conjugate.

Note: Other protocol-defined inclusion/exclusion may apply.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Part A, B, C	PRO1184	PRO1184 monotherapy in escalating doses in Part A and at the recommended dose in Part B and C.
Part D1	PRO1184 intravenous infusion of PRO1184	PRO1184 in combination with carboplatin
Part D3	PRO1184 intravenous infusion of PRO1184	PRO1184 in combination with pembrolizumab
Part D2	PRO1184 intravenous infusion of PRO1184	PRO1184 in combination with bevacizumab

Primary Outcome Measures

Name	Time	Method
Parts A, B, and D - Type, Incidence, and Severity of Laboratory Abnormalities	Through end of treatment, up to approximately 1 year.
Parts A, B, and D - Incidence of Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability]	Through end of treatment, up to approximately 1 year.	Type, incidence, severity, and seriousness of adverse events
Parts A, and D - Dose Limiting Toxicity (DLT)	At the end of Cycle 1 (each cycle is 21 days)	The proportion of participants experiencing (DLT).
Part C - Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	Through end of treatment, up to approximately 1 year.

Secondary Outcome Measures

Name	Time	Method
Parts C and D - CA-125 Response Determined Using the Gynecologic Cancer Intergroup (GCIG) Criteria	Through end of treatment, up to approximately 1 year
Part C - Type, Incidence, and Severity of Laboratory Abnormalities	Through end of treatment, up to approximately 1 year
Part C - Type, Incidence, Severity, Seriousness as per Common Terminology Criteria for Adverse Events (CTCAE) v5.0, and Relatedness of Adverse Events (AEs)	Through end of treatment, up to approximately 1 year
Trough Concentrations (Ctrough) for PRO1184	Through end of treatment, up to approximately 1 year
Parts A, B, C, and D - Progression-Free Survival (PFS)	Through end of treatment, up to approximately 1 year.	Time from start of treatment to first documented disease progression or death
Parts A, B, and D - ORR	Up to approximately 1 year.	Participants who achieve partial or complete response per RECIST v1.1 criteria.
Parts A, B, C, and D - Duration of Objective Response (DOR)	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.	Time from the first documentation of an objective tumor response (CR or PR) to the first documented tumor progression or death
Parts A, B, and D - Area under the Plasma Concentration Versus Time Curve (AUC) for PRO1184	Through end of treatment, up to approximately 1 year.	Measurement of AUC after the administration of PRO1184.
Parts A, B, and D - Disease Control Rate (DCR)	Up to approximately 1 year.	Participants who achieve stable disease, partial or complete response per RECIST v1.1 criteria.
Apparent Terminal Half-life (t1/2) for PRO1184	Through end of treatment, up to approximately 1 year
Parts A, B, and D - Best Overall Response (BOR)	Up to approximately 1 year.	Best response as assessed by the investigator per RECIST v1.1 criteria for all tumor types other than pleural mesothelioma which will use mRECIST v1.1.
Part C - Overall survival (OS)	Up to approximately 2 years.	Time from the start of study treatment to the date of death from any cause
Parts A, B, and D - Peak Plasma Concentration (Cmax) for PRO1184	Through end of treatment, up to approximately 1 year.	Measurement of maximum plasma concentration after the administration of PRO1184.
Time to Reach Cmax (Tmax) for PRO1184	Through end of treatment, up to approximately 1 year

Trial Locations

Locations (31)

Hunan Cancer Hospital - Phase 1; 🇨🇳 Changsha, Hunan, China

Hunan Cancer Hospital - Thoracic Medicine Dept II; 🇨🇳 Changsha, Hunan, China

University of California Los Angeles Medical Center; 🇺🇸 Los Angeles, California, United States

University of California, San Diego; Moores Cancer Center; 🇺🇸 San Diego, California, United States

USOR Sansum Clinic; 🇺🇸 Santa Barbara, California, United States

USOR Florida Cancer Specialists East; 🇺🇸 West Palm Beach, Florida, United States

Providence Medical Foundation; 🇺🇸 Santa Rosa, California, United States

USOR Florida Cancer Specialists North; 🇺🇸 Saint Petersburg, Florida, United States

USOR Florida Cancer Specialists South; 🇺🇸 Fort Myers, Florida, United States

University of Kansas Medical Center (KUMC); 🇺🇸 Westwood, Kansas, United States

USOR Maryland Oncology Hematology; 🇺🇸 Rockville, Maryland, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

START Midwest; 🇺🇸 Grand Rapids, Michigan, United States

USOR Minnesota Oncology Hematology; 🇺🇸 Maplewood, Minnesota, United States

Women and Infants Hospital of Rhode Island; 🇺🇸 Providence, Rhode Island, United States

USOR Texas Oncology; 🇺🇸 Fort Worth, Texas, United States

Mary Crowley Cancer Research; 🇺🇸 Dallas, Texas, United States

START Mountain Region; 🇺🇸 West Valley City, Utah, United States

USOR Texas Oncology Gulf Coast; 🇺🇸 Woodland, Texas, United States

USOR Virginia Oncology Associates; 🇺🇸 Norfolk, Virginia, United States

USOR Virginia Cancer Specialists; 🇺🇸 Fairfax, Virginia, United States

Cancer hospital, Chinese Academy of Medical Sciences; 🇨🇳 Beijing, Beijing, China

Jilin Cancer Hospital; 🇨🇳 Chang chun, Jilin, China

Fudan University Shanghai Cancer Center - Gynecologic Oncology; 🇨🇳 Shanghai, Shanghai, China

Fudan University Shanghai Cancer Center- Phase 1; 🇨🇳 Shanghai, Shanghai, China

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

USOR HonorHealth; 🇺🇸 Phoenix, Arizona, United States

Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

University of Oklahoma - Health Sciences Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Sarah Cannon Research Institute at Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States

USOR Arizona Oncology Associates; 🇺🇸 Tucson, Arizona, United States