PRO1184 for Advanced Solid Tumors

Ovarian Cancer Clinical Trial

— PRO1184-001  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05579366
• Other study ID #: PRO1184-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 7, 2022
• Est. completion date: April 2026

Study information

• Verified date: April 2024
• Source: ProfoundBio US Co.
• Contact: ProfoundBio Trial Support
• Phone: 1-844-774-4232
• Email: PRO1184-001[@]profoundbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 374
• Est. completion date: April 2026
• Est. primary completion date: October 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 FRa expression (i.e., FRa 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

Related Conditions & MeSH terms

• Breast Adenocarcinoma
• Breast Neoplasms
• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Ovarian Epithelial
• Endometrial Cancer
• Endometrial Neoplasms
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Mesothelioma
• Mesothelioma, Malignant
• Non-small Cell Lung Cancer
• Ovarian Cancer
• Ovarian Neoplasms
• Primary Peritoneal Carcinoma
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

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

Locations

Country	Name	City	State
China	Cancer hospital, Chinese Academy of Medical Sciences	Beijing	Beijing
China	Jilin Cancer Hospital	Chang chun	Jilin
China	Hunan Cancer Hospital - Phase 1	Changsha	Hunan
China	Hunan Cancer Hospital - Thoracic Medicine Dept II	Changsha	Hunan
China	Fudan University Shanghai Cancer Center - Gynecologic Oncology	Shanghai	Shanghai
China	Fudan University Shanghai Cancer Center- Phase 1	Shanghai	Shanghai
United States	USOR Texas Oncology	Abilene	Texas
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	USOR Virginia Cancer Specialists	Fairfax	Virginia
United States	USOR Texas Oncology	Fort Worth	Texas
United States	START Midwest	Grand Rapids	Michigan
United States	University of California Los Angeles Medical Center	Los Angeles	California
United States	Sarah Cannon Research Institute at Tennessee Oncology	Nashville	Tennessee
United States	University of Oklahoma - Health Sciences Center	Oklahoma City	Oklahoma
United States	University of California, San Diego; Moores Cancer Center	San Diego	California
United States	USOR Sansum Clinic	Santa Barbara	California
United States	Providence Medical Foundation	Santa Rosa	California
United States	START Mountain Region	West Valley City	Utah
United States	University of Kansas Medical Center (KUMC)	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
ProfoundBio US Co.

Countries where clinical trial is conducted

United States,  China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Parts A, B, C, and D - Immunogenic potential of PRO1184	Assessment of anti-drug antibodies	Through end of treatment, up to approximately 1 year.
Other	Parts A and B - Overall survival	Time from the start of study treatment to the date of death from any cause	Up to approximately 2 years.
Other	Parts A, B, C, and D - Exploratory biomarkers of PRO1184-mediated and disease-related pharmacodynamic effects		Through end of treatment, up to approximately 1 year.
Other	Part C - 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.
Other	Part C - 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.
Primary	Parts A, B, and D - 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.
Primary	Parts A, B, and D - Dose limiting toxicity	The proportion of patients experiencing dose limiting toxicities	At the end of Cycle 1 (each cycle is 21 days)
Primary	Parts A, B, and D - Type, incidence, and severity of laboratory abnormalities		Through end of treatment, up to approximately 1 year.
Primary	Part C - ORR per RECIST v1.1		Through end of treatment, up to approximately 1 year.
Secondary	Parts A, B, and D - 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.
Secondary	Parts A, B, and D - Objective response rate	Patients who achieve partial or complete response per RECIST v1.1 criteria	Up to approximately 1 year.
Secondary	Parts A, B, and D - Disease control rate	Patients who achieve stable disease, partial or complete response per RECIST v1.1 criteria	Up to approximately 1 year.
Secondary	Parts A, B, C, and D - Progression-free survival	Time from start of treatment to first documented disease progression or death	Through end of treatment, up to approximately 1 year.
Secondary	Part C - Overall survival	Time from the start of study treatment to the date of death from any cause	Up to approximately 2 years.
Secondary	Parts A, B, C, and D - 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.
Secondary	Parts A, B, and D - 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.
Secondary	Parts A, B, and D - 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.
Secondary	Parts C and D - CA-125 response determined using the Gynecologic Cancer Intergroup (GCIG) criteria		Through end of treatment, up to approximately 1 year.
Secondary	Part C - Type, incidence, severity, seriousness as per CTCAE v5.0, and relatedness of adverse events		Through end of treatment, up to approximately 1 year.
Secondary	Part C - Type, incidence, and severity of laboratory abnormalities		Through end of treatment, up to approximately 1 year.