OR502 + Cemiplimab for Cancer

Recruiting at 3 trial 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safety and effectiveness of a new treatment, OR502, for individuals with certain advanced cancers. Researchers are testing OR502 alone and in combination with cemiplimab, an immunotherapy, to evaluate their combined effect on tumors. The trial targets individuals with progressive cancers, such as ovarian or skin cancer, that have not responded well to standard treatments. Participants should have tried other treatments without success and have measurable disease progression. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

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

In earlier studies, OR502 showed promise with a disease control rate of 65%, meaning many patients experienced tumor stabilization or shrinkage. Cemiplimab, when used alone, helped 44% of people with certain skin cancers achieve similar results. Both treatments have undergone previous testing in people.

Cemiplimab has approval for some cancers, indicating general safety. Common side effects include fatigue, nausea, and muscle pain. OR502 remains under study, but it appears well-tolerated so far. This trial is in its early stages and aims to assess the safety of the treatments. Researchers are closely monitoring for any side effects to ensure safety during testing. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for platinum-resistant ovarian cancer and cutaneous squamous cell carcinoma, OR502 offers a novel approach by being administered intravenously either alone or in combination with cemiplimab. This combination is particularly promising because cemiplimab is an immunotherapy that enhances the body's immune response against cancer cells. Researchers are excited about OR502 because it's designed to target these cancers more precisely and potentially with fewer side effects compared to traditional chemotherapy. The ability to use OR502 in combination with cemiplimab could enhance the effectiveness of the treatment by tackling the cancer from multiple angles, offering new hope for patients with these tough-to-treat cancers.

What evidence suggests that OR502 and cemiplimab could be effective for advanced solid tumors?

Studies have shown that cemiplimab can extend the lives of people with advanced skin cancer or certain types of lung cancer. It effectively targets tumors and has FDA approval for serious cases. This trial examines OR502 as a newer treatment for its potential to combat tumors in advanced cancers. Participants will receive OR502 either alone or with cemiplimab to assess its effectiveness in treating hard-to-treat cancers, such as ovarian cancer unresponsive to standard treatments. Although more research is necessary, early signs suggest promise when combined with cemiplimab. ^{2 5 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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 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]

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]

Citations

1. investor.regeneron.com investor.regeneron.com/news-releases/news-release-details/regeneron-showcases-advances-across-oncology-portfolio-and

Release Details Highlights include new Phase 3 C-POST data on an every 6-week dosing regimen for the PD-1 inhibitor Libtayo® (cemiplimab) as adjuvant treatment ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7771329/

Cemiplimab in locally advanced cutaneous squamous cell ... Cemiplimab has shown substantial antitumour activity in patients with metastatic cutaneous squamous cell carcinoma. Patients with locally advanced cutaneous ...

3. oncnursingnews.com oncnursingnews.com/view/fda-approves-cemiplimab-in-high-risk-cutaneous-squamous-cell-carcinoma

FDA Approves Cemiplimab in High-Risk Cutaneous ... The FDA has granted approval to adjuvant cemiplimab treatment for patients with high-risk cutaneous squamous cell carcinoma after surgery ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0959804924006956

Real-life efficacy and safety of cemiplimab in advanced ... This study confirms the feasibility and the replicability of the cemiplimab nominal use in advanced CC, in a real-world practice in Italy.

5. cancernetwork.com cancernetwork.com/view/fda-approves-adjuvant-cemiplimab-in-cutaneous-squamous-cell-carcinoma

FDA Approves Adjuvant Cemiplimab in Cutaneous ... Findings from the phase 3 C-POST trial support the FDA approval of cemiplimab in this cutaneous squamous cell carcinoma population.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/761097s016lbl.pdf

LIBTAYO® (cemiplimab-rwlc) injection, for intravenous use Cemiplimab-rwlc pharmacokinetic data were collected in 1063 patients with various solid tumors. ... cancer called cutaneous squamous cell carcinoma (CSCC).

7. aetna.com aetna.com/cpb/medical/data/900_999/0942.html

Cemiplimab-rwlc (Libtayo) - Medical Clinical Policy Bulletins Libtayo in combination with platinum-based chemotherapy: The most common adverse reactions (≥15%) are alopecia, musculoskeletal pain, nausea, fatigue, ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/761097s014lbl.pdf

LIBTAYO® (cemiplimab-rwlc) injection, for intravenous use What is LIBTAYO? LIBTAYO is a prescription medicine used to treat: • people with a type of skin cancer called cutaneous squamous cell carcinoma (CSCC).