RP3 + Nivolumab for Solid Tumors

Recruiting at 14 trial locations

Overseen By Clinical Trials at Replimune

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Replimune Inc.

Must not be taking: Systemic antivirals, Botanical preparations

Disqualifiers: Viral infections, Pneumonitis, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

123 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment called RP3, which is a modified virus designed to attack cancer cells and help the immune system fight cancer. It targets adult patients with advanced solid tumors who need new treatment options. The virus works by directly killing cancer cells and boosting the body's immune response against the cancer. Reovirus is a double-stranded RNA virus that has shown promise in targeting cancer cells.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you must stop antiviral medications for certain conditions and avoid botanical preparations for 2 weeks before starting the trial.

What data supports the effectiveness of the drug RP3 + Nivolumab for solid tumors?

Research shows that Nivolumab, a part of this drug combination, has been effective in improving survival in patients with certain cancers like lung and kidney cancer by helping the immune system recognize and attack tumor cells. Additionally, anti-PD1 therapies, like Nivolumab, have shown benefits in treating metastatic melanoma, suggesting potential effectiveness in other solid tumors. ^{1 2 3 4 5}

Is the combination of RP3 and Nivolumab generally safe for humans?

Nivolumab, also known as Opdivo, is generally used to treat various cancers, but it can cause serious side effects like blood-related issues and immune system reactions. Some patients have experienced problems like joint pain, muscle inflammation, lung issues, and diarrhea, which can lead to stopping the treatment. ^{4 6 7 8 9}

How is the drug RP3 + Nivolumab different from other treatments for solid tumors?

The combination of RP3 and Nivolumab is unique because it uses an anti-PD1 monoclonal antibody to block a specific pathway (PD-1) that tumors use to hide from the immune system, potentially enhancing the body's ability to fight cancer. This approach is different from traditional chemotherapy, which directly targets and kills cancer cells. ^{2 4 5 6 10}

Research Team

Shaheen Kumar, MD

Principal Investigator

Replimune Inc.

Eligibility Criteria

Adults with advanced solid tumors who've exhausted standard treatments or can't tolerate them, and have at least one measurable tumor. Participants must be in good physical condition (ECOG 0-1), provide tumor biopsy samples, and not have neurological tumors or certain viral infections.

Inclusion Criteria

At least one measurable tumor ≥ 1 cm in longest diameter (or shortest diameter for lymph nodes)

My cancer has spread, and standard treatments haven't worked or aren't suitable for me.

Note: Predefined inclusion criteria may apply for each additional expansion cohort.

Exclusion Criteria

I have a history of lung scarring or fibrosis.

I have treated my hepatitis C at least a month ago.

I regularly take medication for a viral infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation Treatment

Participants receive RP3 alone in dose escalation phase with intratumoral injections

8 weeks

Multiple visits for injections and monitoring

Dose Combination Treatment

Participants receive RP3 in combination with anti-PD1 therapy

Up to 2 years

Regular visits for combination therapy administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

60 days after last dose

Treatment Details

Interventions

• anti-PD1 monoclonal antibody
• Nivolumab
• RP3

Trial Overview The study is testing RP3 alone and combined with Nivolumab to find the safest dose for Phase 2 trials. It's an early-stage trial (Phase 1) involving adults with advanced solid tumors to assess safety, tolerability, and optimal dosing.

Participant Groups

Group I: Seronegative cohort Experimental Treatment 1 Intervention

Doses of RP3 (IT) in HSV seronegative participants.

Group II: Dose escalation of RP3 - superficial and/or deep/visceral tumors Experimental Treatment 1 Intervention

Dose escalation of RP3 alone in 2 cohorts with intratumoral (IT) injections including use of imaging guided injection for deep tumors.

Group III: Dose combination of RP3 and anti-PD1 therapy - superficial and/or deep/visceral tumors Experimental Treatment 2 Interventions

Dose combination of RP3 and anti-PD1 therapy. IT injections of RP3 including use of imaging guided injection for deep tumors.

Who Is Running the Clinical Trial?

Replimune Inc.

Lead Sponsor

Trials

16

Recruited

1,700+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Findings from Research

Nivolumab, a monoclonal antibody that targets PD-1, has been shown to significantly improve overall survival in patients with metastatic renal cell carcinoma (RCC) compared to the standard treatment everolimus, especially after first-line antiangiogenic therapy.

Ongoing research aims to identify which patients will benefit the most from nivolumab and to explore its effectiveness in combination with other treatments, highlighting the need for further studies in the field of immunotherapy for RCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics and clinical efficacy of nivolumab in the treatment of metastatic renal cell carcinoma. Farolfi, A., Schepisi, G., Conteduca, V., et al.[2018]

In a study of 85 metastatic melanoma patients treated with anti-PD1 therapy, those with undetectable circulating tumor DNA (ctDNA) at baseline showed significantly better progression-free survival (PFS) and overall survival (OS) compared to those with detectable ctDNA, indicating ctDNA levels can be a predictive biomarker for treatment outcomes.

Patients with high ctDNA levels (>500 copies/ml) at baseline or week 3 had poorer clinical outcomes, suggesting that monitoring ctDNA can provide valuable insights into tumor burden and response to therapy during anti-PD1 treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Undetectable circulating tumor DNA (ctDNA) levels correlate with favorable outcome in metastatic melanoma patients treated with anti-PD1 therapy. Seremet, T., Jansen, Y., Planken, S., et al.[2023]

In a phase 3 study involving 582 patients with advanced nonsquamous non-small-cell lung cancer (NSCLC), nivolumab significantly improved overall survival compared to docetaxel, with a median survival of 12.2 months versus 9.4 months, respectively.

Nivolumab also had a much lower rate of severe treatment-related adverse events (10%) compared to docetaxel (54%), indicating a better safety profile while maintaining efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. Borghaei, H., Paz-Ares, L., Horn, L., et al.[2022]

The combination of nivolumab (10 mg/kg) with standard chemotherapy was well tolerated in patients with advanced non-small-cell lung cancer (NSCLC), with only one case of dose-limiting toxicity observed among 24 patients across four treatment arms.

Nivolumab combined with chemotherapy showed promising antitumor activity, with median progression-free survival ranging from 3.15 months to 9.63 months, indicating its potential effectiveness in treating advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of nivolumab and standard chemotherapy drug combination in patients with advanced non-small-cell lung cancer: a four arms phase Ib study. Kanda, S., Goto, K., Shiraishi, H., et al.[2022]

In a meta-analysis of five studies involving 2399 patients, nivolumab was found to significantly lower the risk of hematological toxicities such as anemia, neutropenia, and leukopenia compared to other treatments.

The relative risks for these conditions were notably low, indicating that nivolumab may be a safer option regarding hematological side effects, which is important for clinicians when considering treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The risks of hematological toxicities of nivolumab in cancer patients: A PRISMA-compliant meta-analysis. Shi, Z., Liu, X., Chen, M., et al.[2023]

In a study of 271 advanced non-small-cell lung cancer patients treated with PD-1 antibodies, 42.8% experienced immune-related adverse events (irAEs), which were linked to lower overall survival (OS) rates, particularly in those with severe irAEs like colitis.

Patients who required treatment interruption due to irAEs had significantly lower OS compared to those who continued therapy, highlighting the need for better management strategies for irAEs to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Nivolumab and Pembrolizumab in Patients With Advanced Non-Small-Cell Lung Cancer Needing Treatment Interruption Because of Adverse Events: A Retrospective Multicenter Analysis. Ksienski, D., Wai, ES., Croteau, N., et al.[2019]

References

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

Modulation of intratumoural myeloid cells, the hallmark of the anti-tumour efficacy induced by a triple combination: tumour-associated peptide, TLR-3 ligand and α-PD-1. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics and clinical efficacy of nivolumab in the treatment of metastatic renal cell carcinoma. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Undetectable circulating tumor DNA (ctDNA) levels correlate with favorable outcome in metastatic melanoma patients treated with anti-PD1 therapy. [2023]

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

Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. [2022]

5. China pubmed.ncbi.nlm.nih.gov

[Preparation and characterization of three novel monoclonal antibodies against human PD-L1]. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of nivolumab and standard chemotherapy drug combination in patients with advanced non-small-cell lung cancer: a four arms phase Ib study. [2022]

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

Durable Clinical Benefit in Metastatic Renal Cell Carcinoma Patients Who Discontinue PD-1/PD-L1 Therapy for Immune-Related Adverse Events. [2022]

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

The risks of hematological toxicities of nivolumab in cancer patients: A PRISMA-compliant meta-analysis. [2023]

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

Efficacy of Nivolumab and Pembrolizumab in Patients With Advanced Non-Small-Cell Lung Cancer Needing Treatment Interruption Because of Adverse Events: A Retrospective Multicenter Analysis. [2019]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Nivolumab drug holiday in patients treated for metastatic renal cell carcinoma: A real-world, single-centre experience. [2022]