Print

Purpose

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).

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 Part C: High grade ovarian cancer: - Patients must have platinum-resistant/refractory ovarian cancer - Patients must have received prior bevacizumab - Patients with known or suspected deleterious germline or somatic BRCA mutations must have been treated with a poly ADP-ribose polymerase (PARP) inhibitor - Patients must have previously received mirvetuximab soravtansine, if indicated based on an FDA approved test for FRα expression (i.e., FRα PS2+ membrane expression in at least 75% of tumor cells), 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 patient preference (and not disease progression) is not considered a separate line of therapy Part D: Cohort D1 (PRO1184+carboplatin): - Patients must have platinum-sensitive ovarian cancer - Patients must have received 1 to 3 prior lines of therapy Cohort D2 (PRO1184+bevacizumab): -Patients must have platinum-resistant/refractory ovarian cancer Cohort D3 (PRO1184+pembrolizumab): - Endometrial cancer (any subtype excluding sarcoma) - Patients must have received prior platinum-based chemotherapy for recurrent or advanced disease

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 CYP3A inhibitor within 14 days (dose escalation only) - prior therapy with a topoisomerase 1 inhibitor-based antibody drug conjugate - additional protocol defined inclusion/exclusion criteria may apply

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Single Group Assignment
Intervention 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.
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Part A, B, C 		PRO1184 monotherapy in escalating doses in Part A and at the recommended dose in Part B and C.
  • Drug: PRO1184
    Intravenous infusion of PRO1184
Experimental
Part D1 		PRO1184 in combination with carboplatin
  • Drug: PRO1184 intravenous infusion of PRO1184
    Carboplatin intravenous infusion
Experimental
Part D2 		PRO1184 in combination with bevacizumab
  • Drug: PRO1184 intravenous infusion of PRO1184
    Bevacizumab intravenous infusion
Experimental
Part D3 		PRO1184 in combination with pembrolizumab
  • Drug: PRO1184 intravenous infusion of PRO1184
    Pembrolizumab intravenous infusion

Recruiting Locations

University of Kansas Medical Center (KUMC)
Westwood, Kansas 66205

More Details

Status
Recruiting
Sponsor
ProfoundBio US Co.

Study Contact

ProfoundBio Trial Support
1-844-774-4232
PRO1184-001@profoundbio.com

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 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. The study consists of 4 main parts: Part A: dose-escalation cohorts Part B: tumor-specific monotherapy dose-expansion cohorts Part C: ovarian cancer extension cohort Part D: combination therapy cohorts 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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.