ONC-392 and Pembrolizumab in Platinum Resistant Ovarian Cancer

Ovarian Cancer Clinical Trial

— PRESERVE-004  

Official title:

Phase 2 Randomized Open-label Multicenter Study of Combination of ONC-392 and Pembrolizumab for the Treatment of Patients With Platinum Resistant Ovarian Cancer (PROC)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05446298
• Other study ID #: PRESERVE-004
• Secondary ID: KNE24 and MK3475
• Status: Recruiting
• Phase: Phase 2
• Start date: December 22, 2022
• Est. completion date: June 30, 2026

Study information

• Verified date: January 2024
• Source: OncoC4, Inc.
• Contact: Pan Zheng, MD, PhD
• Phone: 2027516823
• Email: pzheng[@]oncoc4.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 58
• Est. completion date: June 30, 2026
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Ovarian Cancer
• Ovarian Neoplasms
• Primary Peritoneal Carcinoma

Intervention

Drug:
• ONC-392
ONC-392 will be given by IV infusion, q3w.
• Pembrolizumab
Pembrolizumab in fixed dose of 200 mg will be given by IV infusion, q3w.

Locations

Country	Name	City	State
United States	Women's Cancer Care Associates, LLC. 405	Albany	New York
United States	Texas Oncology, P. A. - Austin, USOR. 417	Austin	Texas
United States	The Ohio State University James Cancer Center, 412	Columbus	Ohio
United States	Nuvance Health System, 401	Danbury	Connecticut
United States	Northwest Cancer Centers - Dyer, IN - USOR, 422	Dyer	Indiana
United States	Oncology Associates of Oregon, P. C. - USOR. 419	Eugene	Oregon
United States	Texas Oncology, P.A., Fort Worth - USOR. 420	Fort Worth	Texas
United States	Cancer Treatment Centers of America, Phoenix. 403	Goodyear	Arizona
United States	Sudarshan Sharma, MD. LTD. 414	Hinsdale	Illinois
United States	Baptist MD Anderson Cancer Center, 404	Jacksonville	Florida
United States	Baptist Health Lexington, 407	Lexington	Kentucky
United States	Norton Cancer Institute - St. Matthews, 416	Louisville	Kentucky
United States	Minnesota Oncology Hematology, P. A. - USOR, 421	Maplewood	Minnesota
United States	Medical College of Wisconsin, 408	Milwaukee	Wisconsin
United States	Honor Health, USOR, 406	Phoenix	Arizona
United States	Center of Hope, 413	Reno	Nevada
United States	The Valley Hosptial, Inc. 411	Ridgewood	New Jersey
United States	Willis-Knighton Physician Network / Gynecologic Oncology Associates, 409	Shreveport	Louisiana
United States	Texas Oncology, P. A. Woodlands - USOR, 418	The Woodlands	Texas
United States	Texas Oncology - Northeast Texas - USOR, 423	Tyler	Texas
United States	Cancer Treatment Centers of America, Chicago. 410	Zion	Illinois

Sponsors (3)

Lead Sponsor	Collaborator
OncoC4, Inc.	GOG Foundation, Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR)	To assess the efficacy of ONC-392 and pembrolizumab combination therapy in objective response rate per RECIST1.1.	24 months
Primary	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	Duration of Response (DoR)	To assess the efficacy of ONC-392 and pembrolizumab combination therapy measured by duration of response.	24 months
Secondary	Disease Control Rate (DCR)	To assess the efficacy of ONC-392 and pembrolizumab combination therapy measured by DCR.	24 months
Secondary	Best Overall Response (BOR)	To assess the efficacy of ONC-392 and pembrolizumab combination therapy measured by BOR.	24 months
Secondary	Progression Free Survival (PFS)	PFS as assessed by BICR according to RECIST 1.1 and iRECIST.	24 months
Secondary	Overall Survival (OS)	OS as assessed from randomization to the time the subject expired.	24 months
Secondary	Pharmacokinetics and exposure-response analysis	Drug concentration measurement in relation to safety and efficacy	24 months