What side effects are associated with this type of intervention?

Common treatments for ovarian cancer include chemotherapy agents like carboplatin and paclitaxel, which often cause side effects such as nausea, fatigue, hair loss, and increased risk of infection. Targeted therapies like PARP inhibitors (e.g., olaparib) can lead to anemia, nausea, and fatigue. Anti-CTLA4 monoclonal antibodies, similar to ONC-392, are associated with immune-related side effects such as skin reactions, endocrine disorders, and gastrointestinal issues. These treatments can also cause more severe adverse events like pneumonitis and hepatitis.

What prior FDA approvals exist?

The FDA has approved several immunotherapy drugs for the treatment of ovarian cancer, although none specifically targeting CTLA-4 like ONC-392. Notable approvals include pembrolizumab, a PD-1 inhibitor, for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors. Additionally, PARP inhibitors such as olaparib, niraparib, and rucaparib have been approved for ovarian cancer, particularly in patients with BRCA mutations or those who have responded to platinum-based chemotherapy. These treatments represent significant advancements in the management of ovarian cancer, leveraging the body's immune system to target cancer cells.

What other types of research exist?

Promising novel alternatives to ONC-392 for ovarian cancer patients in 2024 include: 1) Pembrolizumab (anti-PD-1 antibody), which has shown efficacy in various solid tumors including ovarian cancer. 2) Atezolizumab (anti-PD-L1 antibody), which has been effective in multiple cancer types and is being explored in ovarian cancer. 3) Niraparib (PARP inhibitor), particularly for patients with BRCA mutations or homologous recombination deficiency. 4) Bevacizumab (anti-VEGF antibody), which has been used in combination with chemotherapy for ovarian cancer. These therapies represent the forefront of immunotherapy and targeted therapy for ovarian cancer.

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Monoclonal Antibodies

ONC-392 + Pembrolizumab for Non-Small Cell Lung Cancer (PRESERVE-001 Trial)

Phase 1 & 2

Recruiting

Led By Tianhong Li, MD

Research Sponsored by OncoC4, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patient must have a performance status of 0 or 1 on the ECOG Performance Scale

Female and Male patients must agree to use adequate methods of contraception starting with the first dose of study drug through 90 days after the last dose of study therapy

Must not have

Patients who are on chronic systemic steroid therapy at doses >10 mg/day

Patients who have active symptomatic brain metastasis or leptomeningeal metastasis

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 year

Awards & highlights

No Placebo-Only Group

Summary

This trial tests ONC-392, an antibody that helps the immune system fight cancer, in patients with advanced or spreading tumors who haven't responded to other treatments. It works by blocking a protein that usually keeps immune responses in check, making it easier for the body to attack cancer cells.

Who is the study for?

Adults over 18 with certain advanced solid tumors or NSCLC, who have measurable disease and are in good physical condition. They must not be on high-dose steroids, pregnant, breastfeeding, or have brain metastases. Participants need functioning organs and agree to use contraception.

What is being tested?

The trial is testing ONC-392 alone and combined with Pembrolizumab in patients with various cancers including NSCLC. It's a first-in-human study assessing safety, how the body processes the drug (pharmacokinetics), and effectiveness.

What are the potential side effects?

Potential side effects include immune-related reactions due to ONC-392 or Pembrolizumab such as inflammation of organs, infusion reactions like fever or chills, fatigue, skin rash, digestive issues like diarrhea or liver enzyme changes.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am fully active or restricted in physically strenuous activity but can do light work.

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I agree to use birth control from the first to 90 days after the last dose of the study drug.

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My organ functions are within normal ranges according to recent tests.

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I have a confirmed diagnosis of NSCLC or another type of cancer, with it spreading or getting worse.

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My adenoid cystic carcinoma has worsened in the last 12 months.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am on long-term steroid treatment with doses over 10 mg/day.

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I have active brain or spinal cord cancer symptoms.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ one year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~one year

This trial's timeline: 3 weeks for screening, Varies for treatment, and one year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Dose limiting toxicity (DLT) in monotherapy

Maximal tolerable dose (MTD) in monotherapy

Rate of treatment related adverse events (TRAE) according to CTCAE v5.0

+1 more

Secondary study objectives

Objective Response Rate (ORR)

Overall Survival (OS)

Progression Free Survival (PFS)

+2 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Group I: ONC-392 in combination with pembrolizumabExperimental Treatment2 Interventions

The Part B1 study will test ONC-392 intravenous (IV) infusion, Q3W, in combination with fixed dose of pembrolizumab. The dose for pembrolizumab will be fixed at 200mg/cycle dosed every 21 days (Q3W). The Part B1 will start at one level below RP2D-M dose for ONC-392 and 200mg of pembrolizumab. When 2 DLTs occur before 6 patients are enrolled, the ONC-392 dose will be decreased to the next dose level until ≤ 1/6 patients treated at that dose develops a DLT. This dose level will be designated RP2D-C. 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 small cell lung cancer, and metastatic melanoma.

Group II: ONC-392 and docetaxelExperimental Treatment2 Interventions

Part E Arm O will test ONC-392 in combination with docetaxel, IV infusion, Q3W, in PD-1 resistant NSCLC patients.

Group III: ONC-392 Treatment as single agentExperimental Treatment1 Intervention

The Part A study will test ONC-392 intravenous (IV) infusion up to five predefined dose levels from 0.1 mg/kg to 10 mg/kg ONC-392 as monotherapy every 21 days (Q3W). The Part A study will determine the maximal tolerable dose (MTD) and the recommended Phase 2 dose in monotherapy (RP2D-M). In Part C, Arms A-C, I-N monotherapy expansion cohorts will further assess the safety and efficacy of ONC-392 in different dose levels as monotherapy in pancreatic cancer, triple negative breast cancer, non small cell lung cancer with driver mutations, PD-1 resistant non small cell lung cancer, PD-1 resistant melanoma, head and neck cancer, ovarian cancer, renal cell carcinoma and other solid tumors. Part D is a Phase II study on recurrent and/or metastatic adenoid cystic carcinoma.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab

2017

Completed Phase 3

~3150

Docetaxel

1995

Completed Phase 4

~6550

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for ovarian cancer include chemotherapy, targeted therapy, and immunotherapy. Chemotherapy works by killing rapidly dividing cancer cells, while targeted therapies, such as PARP inhibitors, interfere with specific molecular pathways involved in cancer cell survival. Immunotherapy, including anti-CTLA4 monoclonal antibodies like ONC-392, enhances the immune system's ability to recognize and destroy cancer cells by blocking inhibitory signals that prevent immune activation. This is crucial for ovarian cancer patients as it offers a potential for more effective and personalized treatment options, especially for those with advanced or resistant disease.

Defining the molecular response to trastuzumab, pertuzumab and combination therapy in ovarian cancer.