ONC-392 and Pembrolizumab in Platinum Resistant Ovarian Cancer

NCT05446298 | Active Not Recruiting Phase 2 FDA Drug

• 4 other identifiers: PRESERVE-004KEYNOTE-E24 and MK3475-E24GOG-308120224734
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 21

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.

Conditions

Ovarian Cancer; Primary Peritoneal Carcinoma; Fallopian Tube Cancer; High Grade Serous Adenocarcinoma of Ovary

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR)

  To assess the efficacy of ONC-392 and pembrolizumab combination therapy in objective response rate per RECIST1.1.

  24 months

• Treatment Related Adverse Events (TRAEs) and Immune Related Adverse Events (irAEs)

  To assess the safety of ONC-392 and pembrolizumab combination therapy

  24 months

Secondary Outcomes (6)

• Duration of Response (DoR)

  24 months

• Disease Control Rate (DCR)

  24 months

• Best Overall Response (BOR)

  24 months

• Progression Free Survival (PFS)

  24 months

• Overall Survival (OS)

  24 months

Study Arms (2)

1 mg/kg ONC-392 and 200 mg pembrolizumab

EXPERIMENTAL

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.

Drug: ONC-392; Drug: Pembrolizumab

2 mg/kg ONC-392 and 200 mg pembrolizumab

EXPERIMENTAL

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.

Drug: ONC-392; Drug: Pembrolizumab

Interventions

ONC-392 DRUG

ONC-392 will be given by IV infusion, q3w.

Also known as: A humanized anti-CTLA4 IgG1 monoclonal antibody made by OncoC4, Inc.

1 mg/kg ONC-392 and 200 mg pembrolizumab; 2 mg/kg ONC-392 and 200 mg pembrolizumab

Pembrolizumab DRUG

Pembrolizumab in fixed dose of 200 mg will be given by IV infusion, q3w.

Also known as: MK3475, Keytruda

1 mg/kg ONC-392 and 200 mg pembrolizumab; 2 mg/kg ONC-392 and 200 mg pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 yrs old female patients who provide written informed consent for the study.
• Patients must have a confirmed diagnosis of high-grade serous ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.
• Patients must have received prior standard of care of surgical intervention, including hysterectomy and salpingo-oophorectomy.
• Patients must have platinum-resistant disease:
• 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.
• 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.
• 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:
• Adjuvant ± neoadjuvant is considered 1 line of therapy
• Maintenance therapy (eg, bevacizumab, PARP inhibitors) will be considered part of the preceding line of therapy (ie, not counted independently)
• Therapy changed due to toxicity in the absence of progression will be considered part of the same line (ie, not counted independently)
• Hormonal therapy will be counted as a separate line of therapy unless it was given as maintenance.
• At least 1 measurable target lesion according to RECIST 1.1, including the following criteria:
• Non-nodal lesion that measures ≥1.0 cm in the longest diameter
• Lymph node (LN) lesion that measures as ≥1.5 cm in the short axis

You may not qualify if:

• 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.
• 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.
• Patients who are at high risk for disease progression including those who have ascites requiring a paracentesis within 14 days before first treatment.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Any evidence of current interstitial lung disease (ILD) or pneumonitis, or a prior history of ILD or non-infectious pneumonitis that required steroid treatment.
• Patients who have active inflammatory bowel disease or intestinal obstruction.
• 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.
• 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.
• 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.
• Patient who had an allogenic tissue/organ transplant or stem cell transplantation will be excluded.

Sponsors & Collaborators

• OncoC4, Inc.: lead
• Merck Sharp & Dohme LLC: collaborator
• GOG Foundation: collaborator

Study Sites (21)

Cancer Treatment Centers of America, Phoenix. 403

Goodyear, Arizona, 85338, United States

Location

Honor Health, USOR, 406

Phoenix, Arizona, 85082, United States

Location

Nuvance Health System, 401

Danbury, Connecticut, 06856, United States

Location

Baptist MD Anderson Cancer Center, 404

Jacksonville, Florida, 32207, United States

Location

Sudarshan Sharma, MD. LTD. 414

Hinsdale, Illinois, 60521, United States

Location

Cancer Treatment Centers of America, Chicago. 410

Zion, Illinois, 60099, United States

Location

Northwest Cancer Centers - Dyer, IN - USOR, 422

Dyer, Indiana, 46311, United States

Location

Baptist Health Lexington, 407

Lexington, Kentucky, 40503, United States

Location

Norton Cancer Institute - St. Matthews, 416

Louisville, Kentucky, 40207, United States

Location

Willis-Knighton Physician Network / Gynecologic Oncology Associates, 409

Shreveport, Louisiana, 71103, United States

Location

Minnesota Oncology Hematology, P. A. - USOR, 421

Maplewood, Minnesota, 55109, United States

Location

Center of Hope, 413

Reno, Nevada, 89511, United States

Location

The Valley Hosptial, Inc. 411

Ridgewood, New Jersey, 07450, United States

Location

Women's Cancer Care Associates, LLC. 405

Albany, New York, 12208, United States

Location

The Ohio State University James Cancer Center, 412

Columbus, Ohio, 43210, United States

Location

Oncology Associates of Oregon, P. C. - USOR. 419

Eugene, Oregon, 97401, United States

Location

Texas Oncology, P. A. - Austin, USOR. 417

Austin, Texas, 78731, United States

Location

Texas Oncology, P.A., Fort Worth - USOR. 420

Fort Worth, Texas, 76104, United States

Location

Texas Oncology, P. A. Woodlands - USOR, 418

The Woodlands, Texas, 77380, United States

Location

Texas Oncology - Northeast Texas - USOR, 423

Tyler, Texas, 75702, United States

Location

Medical College of Wisconsin, 408

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (4)

• Zhang Y, Du X, Liu M, Tang F, Zhang P, Ai C, Fields JK, Sundberg EJ, Latinovic OS, Devenport M, Zheng P, Liu Y. Hijacking antibody-induced CTLA-4 lysosomal degradation for safer and more effective cancer immunotherapy. Cell Res. 2019 Aug;29(8):609-627. doi: 10.1038/s41422-019-0184-1. Epub 2019 Jul 2.

  PMID: 31267017 BACKGROUND

• Du X, Liu M, Su J, Zhang P, Tang F, Ye P, Devenport M, Wang X, Zhang Y, Liu Y, Zheng P. Uncoupling therapeutic from immunotherapy-related adverse effects for safer and effective anti-CTLA-4 antibodies in CTLA4 humanized mice. Cell Res. 2018 Apr;28(4):433-447. doi: 10.1038/s41422-018-0012-z. Epub 2018 Feb 20.

  PMID: 29463898 BACKGROUND

• Barlin JN, Lim PC, Thomes Pepin J, Hopp EE, Cloven NG, Lee C, Eshed HD, Black D, Cottrill HM, Hand L, O'Malley DM, Chuang LT, Willmott L, Chisamore M, Shpyro S, Durbin J, Zheng P, Liu Y, Monk BJ. LBA32 A randomized, phase II, dose optimization of gotistobart, a pH-sensitive anti-CTLA-4, in combination with standard dose pembrolizumab in platinum-resistant recurrent ovarian cancer: Safety, efficacy and dose optimization (PRESERVE-004/GOG-3081). Annals of Oncology, 2024. 35: p. S1224-S1225. doi: 10.1016/j.annonc.2024.08.2271

  RESULT

• Barlin JN, Lim PC, Thomes Pepin J, Hopp EE, Cloven NG, Eshed HD, Black D, Cottrill HM, Hand L, O'Malley DM, Chuang LT, Chisamore M, Durbin J, Zheng P, Liu Y, Shpyro S, Monk BJ.LB010/#1590 A phase 2 randomized dose optimization trial of gotistobart, a PH-sensitive anti-CTLA-4, in combination with pembrolizumab in platinum-resistant ovarian cancer (PROC, preserve-004/GOG-3081; NCT05446298). International Journal of Gynecological Cancer, 2024. 34: p. A6-A8. doi: 10.1136/ijgc-2024-IGCS.7

  RESULT

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases

Study Officials

• Bradley Monk, MD

  GOG Partners

  PRINCIPAL INVESTIGATOR

• Joyce Barlin, MD

  GOG Partners

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2022
• First Posted: July 6, 2022
• Study Start: December 22, 2022
• Primary Completion (Estimated): August 30, 2026
• Study Completion (Estimated): August 30, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (21)