PRESERVE-004 (GOG-3081)

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)

Objective

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.

Study Arms

• Experimental: 3 mg/kg ONC-392 and 200 mg pembrolizumab
• Experimental: 6 mg/kg ONC-392 and 200 mg pembrolizumab

Eligibility

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:
    1. 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.
    2. AST, ATL ≤3 × ULN (≤5 × ULN for participants with liver metastases) Serum Albumin ≥ 2.5 g/dL

NCT ID

NCT05446298