PRO1184 for Advanced Solid Tumors (PRO1184-001)

• ClinicalTrials.gov Identifier: NCT05579366
• Recruitment Status: Recruiting
• First Posted: October 13, 2022
• Last Update Posted: May 3, 2024
• Sponsor: ProfoundBio US Co.
• Information provided by (Responsible Party): ProfoundBio US Co.

Tracking Information

• First Submitted Date: October 4, 2022
• First Posted Date: October 13, 2022
• Last Update Posted Date: May 3, 2024
• Actual Study Start Date: December 7, 2022
• Estimated Primary Completion Date: October 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 30, 2024)

• Parts A, B, and D - Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: Through end of treatment, up to approximately 1 year. ]
  Type, incidence, severity, and seriousness of adverse events
• Parts A, B, and D - Dose limiting toxicity [ Time Frame: At the end of Cycle 1 (each cycle is 21 days) ]
  The proportion of patients experiencing dose limiting toxicities
• Parts A, B, and D - Type, incidence, and severity of laboratory abnormalities [ Time Frame: Through end of treatment, up to approximately 1 year. ]
• Part C - ORR per RECIST v1.1 [ Time Frame: Through end of treatment, up to approximately 1 year. ]

Original Primary Outcome Measures (submitted: October 11, 2022)

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

Current Secondary Outcome Measures (submitted: April 30, 2024)

• Parts A, B, and D - Best Overall Response [ Time Frame: Up to approximately 1 year. ]
  Best response per RECIST v1.1 criteria for all tumor types other than pleural mesothelioma which will use mRECIST v1.1
• Parts A, B, and D - Objective response rate [ Time Frame: Up to approximately 1 year. ]
  Patients who achieve partial or complete response per RECIST v1.1 criteria
• Parts A, B, and D - Disease control rate [ Time Frame: Up to approximately 1 year. ]
  Patients who achieve stable disease, partial or complete response per RECIST v1.1 criteria
• Parts A, B, C, and D - Progression-free survival [ Time Frame: Through end of treatment, up to approximately 1 year. ]
  Time from start of treatment to first documented disease progression or death
• Part C - Overall survival [ Time Frame: Up to approximately 2 years. ]
  Time from the start of study treatment to the date of death from any cause
• Parts A, B, C, and D - Duration of objective response [ Time Frame: 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 - Peak Plasma Concentration (Cmax) for PRO1184 [ Time Frame: Through end of treatment, up to approximately 1 year. ]
  Measurement of maximum plasma concentration after the administration of PRO1184.
• Parts A, B, and D - Area under the plasma concentration versus time curve (AUC) for PRO1184 [ Time Frame: Through end of treatment, up to approximately 1 year. ]
  Measurement of AUC after the administration of PRO1184.
• Parts C and D - CA-125 response determined using the Gynecologic Cancer Intergroup (GCIG) criteria [ Time Frame: Through end of treatment, up to approximately 1 year. ]
• Part C - Type, incidence, severity, seriousness as per CTCAE v5.0, and relatedness of adverse events [ Time Frame: Through end of treatment, up to approximately 1 year. ]
• Part C - Type, incidence, and severity of laboratory abnormalities [ Time Frame: Through end of treatment, up to approximately 1 year. ]

Original Secondary Outcome Measures (submitted: October 11, 2022)

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

Current Other Pre-specified Outcome Measures (submitted: April 30, 2024)

• Parts A, B, C, and D - Immunogenic potential of PRO1184 [ Time Frame: Through end of treatment, up to approximately 1 year. ]
  Assessment of anti-drug antibodies
• Parts A and B - Overall survival [ Time Frame: Up to approximately 2 years. ]
  Time from the start of study treatment to the date of death from any cause
• Parts A, B, C, and D - Exploratory biomarkers of PRO1184-mediated and disease-related pharmacodynamic effects [ Time Frame: Through end of treatment, up to approximately 1 year. ]
• Part C - Peak Plasma Concentration (Cmax) for PRO1184 [ Time Frame: Through end of treatment, up to approximately 1 year. ]
  Measurement of maximum plasma concentration after the administration of PRO1184.
• Part C - Area under the plasma concentration versus time curve (AUC) for PRO1184 [ Time Frame: Through end of treatment, up to approximately 1 year. ]
  Measurement of AUC after the administration of PRO1184.

Original Other Pre-specified Outcome Measures (submitted: October 11, 2022)

Immunogenic potential of PRO1184 [ Time Frame: Through end of treatment, up to approximately 1 year. ]

Assessment of anti-drug antibodies

Descriptive Information

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

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 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.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

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.

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Ovarian Cancer
• High Grade Epithelial Ovarian Cancer
• Primary Peritoneal Carcinoma
• Fallopian Tube Cancer
• Endometrial Cancer
• Non-small Cell Lung Cancer
• Mesothelioma
• Breast Adenocarcinoma
• Triple Negative Breast Cancer
• Hormone Receptor-positive/Her2 Negative Breast Cancer

Intervention

• Drug: PRO1184
  Intravenous infusion of PRO1184
• Drug: PRO1184 intravenous infusion of PRO1184
  Carboplatin intravenous infusion
• Drug: PRO1184 intravenous infusion of PRO1184
  Bevacizumab intravenous infusion
• Drug: PRO1184 intravenous infusion of PRO1184
  Pembrolizumab intravenous infusion

Study Arms

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 30, 2024): 374
• Original Estimated Enrollment (submitted: October 11, 2022): 134
• Estimated Study Completion Date: April 2026
• Estimated Primary Completion Date: October 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: China, United States

Administrative Information

• NCT Number: NCT05579366
• Other Study ID Numbers: PRO1184-001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: ProfoundBio US Co.
• Original Responsible Party: Same as current
• Current Study Sponsor: ProfoundBio US Co.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: ProfoundBio US Co.
• Verification Date: April 2024