ONC-392 + Pembrolizumab for Ovarian Cancer

(PRESERVE-004 Trial)

Not currently recruiting at 21 trial locations

Overseen By Pan Zheng, MD, PhD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: OncoC4, Inc.

Must not be taking: Steroids, Anti-PD-1, CTLA-4

Disqualifiers: Carcinosarcoma, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of combining two medications, ONC-392 (an experimental treatment) and pembrolizumab (an immunotherapy drug), to treat ovarian cancer resistant to platinum-based chemotherapy. Participants should have high-grade serous ovarian cancer, primary peritoneal cancer, or fallopian tube cancer that has not responded well to standard treatments, including surgery and chemotherapy. The trial includes two groups with different doses of ONC-392 to determine which works best with pembrolizumab. Those who have previously tried several cancer therapies and have measurable disease progression may be suitable for this study. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group, offering participants a chance to contribute to important advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that systemic anti-cancer therapy should be stopped for a certain period before starting the study drug. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using ONC-392 with pembrolizumab could benefit people with ovarian cancer unresponsive to platinum-based treatments. Previous studies indicate that this combination is generally safe, with manageable side effects that are usually not serious.

In these studies, most participants tolerated the treatment well. No major safety issues have emerged that would prevent continuation of the treatment. This suggests that combining ONC-392 and pembrolizumab could be a safe option for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because ONC-392, combined with pembrolizumab, offers a novel approach for treating ovarian cancer. Unlike standard treatments like chemotherapy and targeted therapies, ONC-392 works by enhancing the immune system's ability to fight cancer cells. It is a selective IL-2 receptor agonist, which potentially boosts immune response with reduced toxicity. When paired with pembrolizumab, an immune checkpoint inhibitor, this combination could enhance anti-tumor activity, offering a promising alternative to existing options.

What evidence suggests that this trial's treatments could be effective for ovarian cancer?

Research has shown that combining ONC-392 with pembrolizumab may help treat ovarian cancer that doesn't respond to standard platinum-based treatments. In this trial, participants will receive one of two combinations: a 1 mg/kg dose of ONC-392 with pembrolizumab or a 2 mg/kg dose of ONC-392 with pembrolizumab. A study found that the combination reduced tumor size in some patients, with 25% responding to the 1 mg/kg dose and 27.6% responding to the 2 mg/kg dose. Pembrolizumab blocks a pathway that cancer uses to hide from the immune system, while ONC-392 enables the immune system to attack cancer cells through a different pathway. These early results offer hope for those seeking new treatment options. ^{1 2 3 5 6}

Who Is on the Research Team?

Joyce Barlin, MD

Principal Investigator

GOG Partners

Bradley Monk, MD

Principal Investigator

GOG Partners

Are You a Good Fit for This Trial?

This trial is for women over 18 with high-grade serous ovarian, primary peritoneal, or fallopian tube cancer that's resistant to platinum-based therapy. They must have had surgery including hysterectomy and be in good health with a life expectancy of at least 12 weeks. Participants need measurable cancer lesions and adequate organ function but can't join if they're on high-dose steroids, have another active cancer, serious infections recently, certain heart issues within the past year, or specific types of ovarian cancers.

Inclusion Criteria

I finished my targeted radiation therapy at least 2 weeks ago.

I have been diagnosed with high-grade serous ovarian, primary peritoneal, or fallopian tube cancer.

I have had surgery for my condition, including removal of the uterus and ovaries.

Exclusion Criteria

I needed fluid removed from my abdomen recently due to my condition.

I am taking more than 10 mg/day of steroids for an autoimmune condition or as immunosuppression.

I haven't needed IV antibiotics or been hospitalized for an infection in the last 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ONC-392 and pembrolizumab combination therapy. Pembrolizumab 200 mg is administered by IV infusion over 30 minutes, followed by ONC-392 at either 1.0 mg/kg or 2.0 mg/kg by IV infusion over 60 minutes, every 3 weeks.

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of treatment-related adverse events and progression-free survival.

24 months

What Are the Treatments Tested in This Trial?

Interventions

• ONC-392
• Pembrolizumab

Trial Overview The study tests ONC-392 (a new anti-CTLA-4 antibody) combined with pembrolizumab (an anti-PD-1 antibody) to see how safe and effective they are together against platinum-resistant ovarian cancer. Patients will receive both drugs to determine their impact on this type of cancer.

How Is the Trial Designed?

Group I: 2 mg/kg ONC-392 and 200 mg pembrolizumab Experimental Treatment 2 Interventions

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.

Group II: 1 mg/kg ONC-392 and 200 mg pembrolizumab Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

OncoC4, Inc.

Lead Sponsor

Trials

8

Recruited

1,800+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

GOG Foundation

Collaborator

Trials

48

Recruited

18,500+

Published Research Related to This Trial

In a phase Ib trial involving 26 patients with advanced PD-L1-positive ovarian cancer, pembrolizumab demonstrated a confirmed objective response rate of 11.5%, indicating some level of antitumor activity, with 1 complete response and 2 partial responses observed.

The treatment was generally well-tolerated, with 73.1% of patients experiencing treatment-related adverse events, but no deaths or treatment discontinuations due to these events, suggesting that pembrolizumab has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. Varga, A., Piha-Paul, S., Ott, PA., et al.[2019]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In a study of 317 patients with advanced recurrent ovarian cancer treated with pembrolizumab, no significant associations were found between gene expression signatures and clinical outcomes, indicating that these markers may not be reliable predictors of treatment response.

However, higher densities of specific myeloid cell phenotypes (CD11c+ and CD11c+/MHCII-/CD163-/CD68-) in the tumor microenvironment were positively associated with better outcomes, suggesting that these immune cell populations could play a role in enhancing the efficacy of pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular determinants of clinical outcomes of pembrolizumab in recurrent ovarian cancer: Exploratory analysis of KEYNOTE-100. Ledermann, JA., Shapira-Frommer, R., Santin, AD., et al.[2023]

In a study of 44 women with recurrent ovarian cancer treated with immune checkpoint inhibitors, the overall response rate was 14.2%, with a notable correlation between platinum sensitivity and response in high-grade serous ovarian cancer (HGSOC) patients.

Severe immune-related adverse events (irAEs) occurred in 47.7% of patients, with elevated hepatic or pancreatic enzymes being the most common, and a higher number of gene mutations appeared to protect against these specific adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics and outcomes of patients with recurrent ovarian cancer undergoing early phase immune checkpoint inhibitor clinical trials. Hinchcliff, E., Hong, D., Le, H., et al.[2023]

The combination of pembrolizumab and carboplatin was found to be well-tolerated and showed activity in patients with recurrent platinum-resistant ovarian cancer, with a median overall survival of 11.3 months.

Patients with a higher ratio of peripheral CD8+PD1+Ki67+ T cells to tumor burden had significantly longer overall survival, suggesting this ratio could help identify those who may benefit more from this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab with low-dose carboplatin for recurrent platinum-resistant ovarian, fallopian tube, and primary peritoneal cancer: survival and immune correlates. Liao, JB., Gwin, WR., Urban, RR., et al.[2022]

In a study involving patients with recurrent platinum-resistant ovarian cancer, the combination of pembrolizumab, cisplatin, and gemcitabine resulted in an overall response rate of 60%, but the duration of response was relatively short at 4.9 months.

The addition of pembrolizumab did not show a significant benefit over chemotherapy alone, leading to the decision to close the trial for further accrual after an interim analysis indicated modest outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of cisplatin, gemcitabine and pembrolizumab for platinum-resistant ovarian cancer. Walsh, CS., Kamrava, M., Rogatko, A., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05446298

NCT05446298 | ONC-392 and Pembrolizumab in Platinum ... 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 ...

2. onclive.com onclive.com/view/gotistobart-plus-pembrolizumab-shows-activity-in-platinum-resistant-ovarian-cancer

Gotistobart Plus Pembrolizumab Shows Activity in Platinum ... Gotistobart and pembrolizumab showed antitumor activity in platinum-resistant ovarian cancer with ORRs of 25.0% and 27.6% for 1 mg/kg and 2 mg/ ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)03851-1/fulltext

LBA32 A randomized, phase II, dose optimization ... We report safety and efficacy results of gotistobart + pembrolizumab in a randomized, open-label, multicenter phase 2 trial in patients with PROC. Methods.

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-08423

ONC-392 and Pembrolizumab in Platinum Resistant ... 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,

5. oncoc4.com oncoc4.com/press-releases/oncoc4-announces-first-patient-dosed-in-preserve-004-a-phase-2-clinical-trial-of-onc-392-in-combination-with-keytruda-pembrolizumab-in-patients-with-platinum-resistant-ovarian-cancer/

OncoC4 Announces First Patient Dosed in PRESERVE ... The first patient has been dosed in the Phase 2 combination study of ONC-392, a nextgen target-preserving anti-CTLA-4 antibody and KEYTRUDA (pembrolizumab), ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04140526

NCT04140526 | Safety, PK and Efficacy of ONC-392 in ... In Part C, the expansion cohorts Arm D to G will assess the safety and efficacy of ONC-392 in different dose levels and Pembrolizumab combination therapy in non ...