OR502 + Cemiplimab for Cancer

Recruiting in Fairfax (>99 mi)

+3 other locations

Overseen By Lesley Skingley

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: OncoResponse, Inc.

Must be taking: PD-(L)1 inhibitors

Must not be taking: Immunosuppressive drugs

Disqualifiers: Severe hypersensitivity, CNS tumors, others

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

Compensation: Varies

Number of Visits: 3

168 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an open-label, multicenter, first-in-human dose-escalation and expansion Phase 1-2 study designed to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of OR502 administered as a monotherapy and in combination with cemiplimab in subjects with advanced solid tumors.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, there are certain restrictions, such as a minimum of 2 weeks since the last dose of other hormone therapy and 3 weeks since the last dose of other systemic cancer therapy or radiotherapy. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug cemiplimab for cancer treatment?

Research shows that cemiplimab can improve survival in patients with advanced cutaneous squamous cell carcinoma and non-small cell lung cancer, offering better outcomes compared to some existing treatments like EGFR inhibitors and chemotherapy. ^{1 2 3 4 5}

What makes the drug OR502 + Cemiplimab unique for cancer treatment?

Cemiplimab is a monoclonal antibody that targets the PD-1 pathway, which helps the immune system attack cancer cells, and has shown significant benefits in survival for advanced cancers like cutaneous squamous cell carcinoma. The combination with OR502 may offer a novel approach, potentially enhancing the immune response against cancer, although specific details about OR502's mechanism or benefits are not provided in the available research. ^{1 4 5 6 7}

Eligibility Criteria

Adults with advanced solid tumors, including specific types like carcinoma, sarcoma, or melanoma that can't be treated with surgery. They must have tried standard cancer treatments without success or couldn't tolerate them. Participants need to have good organ function and agree to use effective birth control. Those with severe allergies to monoclonal antibodies or certain health conditions are excluded.

Inclusion Criteria

Histological diagnosis as follows:

Biopsy specimens:

- All subjects must be able to supply an archival tumor tissue specimen. If an archival specimen is not available, subjects may remain eligible with approval of the medical monitor

Exclusion Criteria

- QTc interval ≥ 470 msec by electrocardiogram (ECG)

I haven't taken strong immune system drugs or steroids, except for low-dose prednisone, in the last month.

I have stable brain metastases or a primary CNS tumor and am not on high doses of steroids.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Escalation

Dose-escalation phase to determine the maximum-tolerated dose (MTD), maximum achievable dose, or optimal dose of OR502 for further evaluation as monotherapy and in combination with cemiplimab

Varies

Every 3 weeks (Q3W)

Dose-Expansion

Expansion phase to further characterize safety, help determine the recommended Phase 2 dose (RP2D) for further development and determine preliminary anti-tumor activity

Varies

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days

Treatment Details

Interventions

• Cemiplimab
• OR502

Trial Overview The trial is testing OR502 alone and combined with cemiplimab in people with advanced solid tumors. It's an early-phase study looking at safety, how the body processes the drugs (pharmacokinetics), their effects on the body (pharmacodynamics), and initial effectiveness against tumors.

Participant Groups

Group I: OR502 monotherapy and combination therapy dose-expansion phase (Part B) Experimental Treatment 2 Interventions

OR502 administered IV at 2 different dose levels identified in Part A as monotherapy or in combination with cemiplimab in subjects with platinum-resistant ovarian cancer and cutaneous squamous cell carcinoma. Cemiplimab will be administered as an IV infusion at a dose of 350 mg.

Group II: OR502 monotherapy and combination therapy dose-escalation phase (Part A) Experimental Treatment 2 Interventions

Escalating repeated doses of OR502 by IV administration as monotherapy or in combination with cemiplimab in subjects with advanced solid tumors. OR502 will be administered once every 3 weeks (Q3W). Cemiplimab will be administered as an IV infusion at a dose of 350 mg.

Who Is Running the Clinical Trial?

OncoResponse, Inc.

Lead Sponsor

Trials

2

Recruited

340+

Findings from Research

Cemiplimab, a PD-1 inhibitor, shows significant improvements in overall survival (OS) and progression-free survival (PFS) compared to EGFR inhibitors and pembrolizumab, with hazard ratios indicating a strong benefit.

In comparison to platinum-based chemotherapy, cemiplimab also demonstrated superior efficacy in improving overall survival for patients with advanced cutaneous squamous cell carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy of cemiplimab versus other systemic treatments for advanced cutaneous squamous cell carcinoma. Keeping, S., Xu, Y., Chen, CI., et al.[2021]

Cemiplimab, a PD-1 inhibitor, demonstrated an objective response rate of 25% in patients with advanced non-small cell lung cancer (NSCLC) who had previously undergone treatment, indicating its potential effectiveness in this challenging patient population.

The treatment was generally well-tolerated, although 60% of patients experienced severe treatment-emergent adverse events, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and antitumor activity of cemiplimab, a human monoclonal anti-PD-1, as monotherapy in patients with pretreated non-small cell lung cancer (NSCLC): Data from the Phase 1 NSCLC expansion cohort. Moreno, V., Garrido, P., Papadopoulos, KP., et al.[2021]

Cemiplimab significantly improves overall survival in patients with advanced non-small cell lung cancer (NSCLC) with high PD-L1 levels, adding 0.546 quality-adjusted life years (QALYs) compared to chemotherapy.

The treatment is considered cost-effective, with an incremental cost-effectiveness ratio of $40,390 per QALY gained, and a 100% probability of being cost-effective at a willingness-to-pay threshold of $150,000 per QALY.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness Analysis of Cemiplimab Versus Chemotherapy as First-Line Treatment in Advanced NSCLC with PD-L1 Expression Levels of at Least 50. Wang, L., Peng, Y., Zeng, X., et al.[2021]

Cemiplimab demonstrated significant antitumor activity in patients with locally advanced cutaneous squamous cell carcinoma, with 44% of the 78 patients showing an objective response, including 13% achieving a complete response.

The treatment had an acceptable safety profile, with 44% of patients experiencing grade 3-4 adverse events, the most common being hypertension and pneumonia, and one treatment-related death due to aspiration pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab in locally advanced cutaneous squamous cell carcinoma: results from an open-label, phase 2, single-arm trial. Migden, MR., Khushalani, NI., Chang, ALS., et al.[2021]

Cemiplimab, a PD-1 targeting monoclonal antibody, demonstrated an objective response rate of 45.5% in a real-life study of 33 patients with advanced cutaneous squamous cell carcinoma, confirming its efficacy as a treatment option.

The addition of radiotherapy to cemiplimab resulted in a quicker response time, with a median duration of response of 5.5 months compared to 3 months for cemiplimab alone, and did not increase adverse events, indicating a safe and effective combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-Life Study of the Benefit of Concomitant Radiotherapy with Cemiplimab in Advanced Cutaneous Squamous Cell Carcinoma (cSCC): A Retrospective Cohort Study. Bailly-Caillé, B., Kottler, D., Morello, R., et al.[2023]

Cemiplimab is a PD-1 monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, which is crucial for enhancing the immune response against cancer cells.

In September 2018, cemiplimab received FDA approval for treating patients with metastatic or locally advanced cutaneous squamous cell carcinoma who cannot undergo curative surgery or radiation, marking a significant advancement in cancer treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab: First Global Approval. Markham, A., Duggan, S.[2023]

In the EMPOWER-Lung 3 study involving 466 patients with advanced non-small cell lung cancer (aNSCLC), cemiplimab combined with chemotherapy significantly improved overall survival (OS) to 21.9 months compared to 13.0 months with placebo, demonstrating its efficacy as a first-line treatment.

While cemiplimab plus chemotherapy showed better survival outcomes, it also resulted in a higher incidence of grade ≥3 adverse events (43.6%) compared to placebo plus chemotherapy (31.4%), indicating a need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: a randomized, controlled, double-blind phase 3 trial. Gogishvili, M., Melkadze, T., Makharadze, T., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Comparative efficacy of cemiplimab versus other systemic treatments for advanced cutaneous squamous cell carcinoma. [2021]

2. Ireland pubmed.ncbi.nlm.nih.gov

Tolerability and antitumor activity of cemiplimab, a human monoclonal anti-PD-1, as monotherapy in patients with pretreated non-small cell lung cancer (NSCLC): Data from the Phase 1 NSCLC expansion cohort. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness Analysis of Cemiplimab Versus Chemotherapy as First-Line Treatment in Advanced NSCLC with PD-L1 Expression Levels of at Least 50. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Cemiplimab in locally advanced cutaneous squamous cell carcinoma: results from an open-label, phase 2, single-arm trial. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Real-Life Study of the Benefit of Concomitant Radiotherapy with Cemiplimab in Advanced Cutaneous Squamous Cell Carcinoma (cSCC): A Retrospective Cohort Study. [2023]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Cemiplimab: First Global Approval. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: a randomized, controlled, double-blind phase 3 trial. [2023]