ONC-392 and Pembrolizumab in Platinum Resistant Ovarian Cancer

Phase 2

Active, not recruiting

• Conditions: Ovarian Cancer; High Grade Serous Adenocarcinoma of Ovary; Primary Peritoneal Carcinoma; Fallopian Tube Cancer
• Interventions: Drug: ONC-392; Drug: Pembrolizumab

• Registration Number: NCT05446298
• Lead Sponsor: OncoC4, Inc.

Brief Summary

This is a study to test the safety and efficacy with the combination of a next generation anti-CTLA-4 antibody, ONC-392, and anti-PD-1 antibody, pembrolizumab, in platinum resistant ovarian cancer patients.

Detailed Description

The purpose of this Phase 2 study is to compare two doses of ONC-392 in combination with a fixed dose of pembrolizumab in participants with ovarian cancer who are resistant to platinum-based chemotherapy and have disease progression on line of therapy containing bevacizumab. Results from this study will be used to inform the study design, patient population, and dose selection for future studies in advanced ovarian cancer.

Study Timeline

• Study First Submitted: 2022-06-30
• Study First Submitted QC: 2022-06-30
• Study First Posted: 2022-07-06
• Study Start: 2022-12-22
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-30
• Last Update Posted: 2025-02-03
• Primary Completion: 2025-06-30
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 58

Inclusion Criteria

1. Age ≥ 18 yrs old female patients who provide written informed consent for the study.

2. Patients must have a confirmed diagnosis of high-grade serous ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.

3. Patients must have received prior standard of care of surgical intervention, including hysterectomy and salpingo-oophorectomy.

4. Patients must have platinum-resistant disease:

   1. Patients who have only 1 line of systemic therapy must have completed a minimum of four cycles of platinum-based therapy with CR or PR and then progressed between 3 to 6 months after the last dose of platinum.
   2. Patients who have received 2 or more lines of platinum therapy must have progressed ≤ 6 months (183 days) after the last dose of platinum.

   The time is calculated from the date of last administrated dose of platinum therapy to the date of radiographic imaging with disease progression.

5. Patients must have received 1 or more prior systemic lines of anti-cancer therapy with or without bevacizumab or a PARP inhibitor, and for whom single-agent therapy is appropriate as the next line of treatment:

   1. Adjuvant ± neoadjuvant is considered 1 line of therapy
   2. Maintenance therapy (eg, bevacizumab, PARP inhibitors) will be considered part of the preceding line of therapy (ie, not counted independently)
   3. Therapy changed due to toxicity in the absence of progression will be considered part of the same line (ie, not counted independently)
   4. Hormonal therapy will be counted as a separate line of therapy unless it was given as maintenance.

6. At least 1 measurable target lesion according to RECIST 1.1, including the following criteria:

   1. Non-nodal lesion that measures ≥1.0 cm in the longest diameter
   2. Lymph node (LN) lesion that measures as ≥1.5 cm in the short axis
   3. The lesion is suitable for repeat measurement using computed tomography/magnetic resonance imaging (CT/MRI). Lesions that have had external beam radiotherapy (EBRT) or locoregional therapy must show radiographic evidence of subsequent growth.

7. ECOG score 0 or 1.

8. Time from prior therapy:

   1. Systemic anti-cancer therapy (5 half-lives of small molecule drugs or 4 weeks, whichever is shorter)
   2. Focal radiation completed at least 2 weeks prior to first dose of study drug.
   3. Major surgery must be completed at least 4 weeks prior to first dose of study drug. Patients have recovered or stabilized from the adverse effects of the prior surgery.

9. In the opinion of the investigator, the patient must have a life expectancy of at least 12 weeks and is well enough to receive experimental therapy.

10. Adequate organ function as determined by laboratory tests as defined below at screening.

System Laboratory Value Hematological Absolutely neutrophil count (ANC) ≥1500/µL Platelets ≥100,000/µL Hemoglobin1 ≥9.0 g/dL or 5.6 mmol/L Renal Creatinine clearance as calculated per Cockcroft-Gault or MDRD formula > 30 mL/min Hepatic Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN except for unconjugated hyperbilirubinemia of Gilbert's syndrome.

AST, ATL ≤3 × ULN (≤5 × ULN for participants with liver metastases) Serum Albumin ≥ 2.5 g/dL

Exclusion Criteria

1. Patients with carcinosarcoma (malignant mixed Mullerian tumor), clear cell carcinoma, endometrioid, low grade serous, clear cell, and mucinous adenocarcinoma, and ovarian cancer not otherwise specified.
2. Patients with primary platinum-refractory disease, defined as disease that did not respond to (CR or PR), or has progressed within 3 months of the last dose of first-line platinum-containing chemotherapy.
3. Patients who are at high risk for disease progression including those who have ascites requiring a paracentesis within 14 days before first treatment.
4. Patients with active symptomatic CNS metastases, unless they have received local therapy (e.g., whole brain radiation therapy [WBRT], surgery or radiosurgery) 21 days before study treatment and have discontinued the use of corticosteroids for this indication for a minimum of 7 days prior to study treatment.
5. Patients who are on chronic systemic steroid therapy for autoimmune conditions or as immunosuppression at doses higher than 10 mg/day prednisone or equivalent within 7 days before first treatment.
6. Active second malignancy with anti-cancer treatments (except for treated in-situ carcinomas [e.g., breast, cervix, bladder], or basal or squamous cell carcinoma of the skin) within the past 24 months. HIV patient with Karposi sarcoma or Castleman disease will be excluded. Patient with renal cell carcinoma will be excluded.
7. Prior history of symptomatic pulmonary embolism or significant cardiovascular impairment within 12 months of the first dose of study drug: such as history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction, or cerebrovascular accident (CVA) stroke, or cardiac arrhythmia associated with hemodynamic instability.
8. Active infection requiring systemic IV antibiotics or hospitalization within 14 days prior to administration of study drugs. Regular treatment of urinary tract infection (UTI) and/or topical treatment are allowed.
9. Patients who have not recovered to CTCAE V5.0 Grade 0 or 1 (except chemotherapy related peripheral neuropathy in Grade 2 or less, or endocrinopathy with adequate replacement therapy) from any toxicity and/or complications from major surgery or prior cancer therapeutics before starting therapy. The hemoglobulin criteria must be met without packed RBC transfusion within 14 days of study treatment.
10. Any evidence of current interstitial lung disease (ILD) or pneumonitis, or a prior history of ILD or non-infectious pneumonitis that required steroid treatment.
11. Patients who have active inflammatory bowel disease or intestinal obstruction.
12. Patients who, in the opinion of the Investigator, have a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, have mental health issues that might interfere with the patient's participation for the full duration of the study or make study participation, or not in the best interest of the patient. The Investigator should discuss with the Sponsor and/or study leaders.
13. Participating in other clinical trials or receiving other anti-cancer therapy. Patient who has prior anti-PD-1, PD-L1, or CTLA-4 antibody based therapies will be excluded.
14. Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention. Note: Administration of killed vaccines are allowed.
15. Patient who had an allogenic tissue/organ transplant or stem cell transplantation will be excluded.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1 mg/kg ONC-392 and 200 mg pembrolizumab	Pembrolizumab	Arm A: Pembrolizumab 200 mg will be administered by IV infusion over 30 minutes, followed by ONC-392 at 1.0 mg/kg will be administered by IV infusion over 60 minutes, q3w.
1 mg/kg ONC-392 and 200 mg pembrolizumab	ONC-392	Arm A: Pembrolizumab 200 mg will be administered by IV infusion over 30 minutes, followed by ONC-392 at 1.0 mg/kg will be administered by IV infusion over 60 minutes, q3w.
2 mg/kg ONC-392 and 200 mg pembrolizumab	ONC-392	Arm B: Pembrolizumab 200 mg will be administered by IV infusion over 30 minutes, followed by ONC-392 at 2.0 mg/kg will be administered by IV infusion over 60 minutes, q3w.
2 mg/kg ONC-392 and 200 mg pembrolizumab	Pembrolizumab	Arm B: Pembrolizumab 200 mg will be administered by IV infusion over 30 minutes, followed by ONC-392 at 2.0 mg/kg will be administered by IV infusion over 60 minutes, q3w.

Primary Outcome Measures

Name	Time	Method
Treatment Related Adverse Events (TRAEs) and Immune Related Adverse Events (irAEs)	24 months	To assess the safety of ONC-392 and pembrolizumab combination therapy
Objective Response Rate (ORR)	24 months	To assess the efficacy of ONC-392 and pembrolizumab combination therapy in objective response rate per RECIST1.1.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics and exposure-response analysis	24 months	Drug concentration measurement in relation to safety and efficacy
Duration of Response (DoR)	24 months	To assess the efficacy of ONC-392 and pembrolizumab combination therapy measured by duration of response.
Disease Control Rate (DCR)	24 months	To assess the efficacy of ONC-392 and pembrolizumab combination therapy measured by DCR.
Overall Survival (OS)	24 months	OS as assessed from randomization to the time the subject expired.
Progression Free Survival (PFS)	24 months	PFS as assessed by BICR according to RECIST 1.1 and iRECIST.
Best Overall Response (BOR)	24 months	To assess the efficacy of ONC-392 and pembrolizumab combination therapy measured by BOR.

Trial Locations

Locations (21)

Cancer Treatment Centers of America, Phoenix. 403; 🇺🇸 Goodyear, Arizona, United States

Honor Health, USOR, 406; 🇺🇸 Phoenix, Arizona, United States

Nuvance Health System, 401; 🇺🇸 Danbury, Connecticut, United States

Baptist MD Anderson Cancer Center, 404; 🇺🇸 Jacksonville, Florida, United States

Sudarshan Sharma, MD. LTD. 414; 🇺🇸 Hinsdale, Illinois, United States

Cancer Treatment Centers of America, Chicago. 410; 🇺🇸 Zion, Illinois, United States

Northwest Cancer Centers - Dyer, IN - USOR, 422; 🇺🇸 Dyer, Indiana, United States

Baptist Health Lexington, 407; 🇺🇸 Lexington, Kentucky, United States

Norton Cancer Institute - St. Matthews, 416; 🇺🇸 Louisville, Kentucky, United States

Willis-Knighton Physician Network / Gynecologic Oncology Associates, 409; 🇺🇸 Shreveport, Louisiana, United States

Minnesota Oncology Hematology, P. A. - USOR, 421; 🇺🇸 Maplewood, Minnesota, United States

Center of Hope, 413; 🇺🇸 Reno, Nevada, United States

The Valley Hosptial, Inc. 411; 🇺🇸 Ridgewood, New Jersey, United States

Women's Cancer Care Associates, LLC. 405; 🇺🇸 Albany, New York, United States

The Ohio State University James Cancer Center, 412; 🇺🇸 Columbus, Ohio, United States

Oncology Associates of Oregon, P. C. - USOR. 419; 🇺🇸 Eugene, Oregon, United States

Texas Oncology, P. A. - Austin, USOR. 417; 🇺🇸 Austin, Texas, United States

Texas Oncology, P.A., Fort Worth - USOR. 420; 🇺🇸 Fort Worth, Texas, United States

Texas Oncology, P. A. Woodlands - USOR, 418; 🇺🇸 The Woodlands, Texas, United States

Texas Oncology - Northeast Texas - USOR, 423; 🇺🇸 Tyler, Texas, United States

Medical College of Wisconsin, 408; 🇺🇸 Milwaukee, Wisconsin, United States