RP3 + Nivolumab for Solid Tumors

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called RP3 for individuals with advanced solid tumors. Researchers aim to assess the safety and tolerability of RP3 both alone and in combination with an anti-PD1 therapy, a type of immunotherapy that aids the immune system in fighting cancer. The trial will explore various doses and combinations of RP3 through direct injections into tumors. Suitable candidates have solid tumors that have worsened despite other treatments or lack other treatment options. Participants must have a tumor that can be measured and injected. 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 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.

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

Research shows that RP3 is being tested for safety in treating advanced solid tumors, both alone and with nivolumab. Earlier studies have used RP3 in people with various solid tumors without causing severe harm.

When combined with nivolumab, a treatment already approved for some cancers, studies have found the combination to be generally safe. Nivolumab has been used successfully in treating conditions like metastatic melanoma, providing some confidence about its safety in these trials.

As this is an early-phase trial, the main goal is to assess the treatment's safety and determine the right dose for future studies. This phase focuses on closely monitoring side effects and ensuring participants can tolerate the treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about RP3 combined with Nivolumab because it offers a novel approach to treating solid tumors. Unlike traditional chemotherapy or radiation, RP3 is an oncolytic virus therapy that works by directly infecting and breaking down cancer cells. This approach is different from standard treatments as it can potentially enhance the body's immune response against tumors. Additionally, the use of imaging-guided intratumoral injections allows for precise delivery of the therapy to both superficial and deep tumors, which might improve effectiveness and reduce side effects. The combination with Nivolumab, an anti-PD1 monoclonal antibody, further enhances immune activation, making this treatment a promising new strategy in cancer care.

What evidence suggests that this trial's treatments could be effective for solid tumors?

Research suggests that RP3 might help treat solid tumors. Early results have shown it to be safe and effective for patients with these cancers. RP3 is a type of treatment called oncolytic immunotherapy, which helps the immune system fight cancer cells.

In this trial, some participants will receive RP3 alone, while others will receive a combination of RP3 and anti-PD1 therapy, such as Nivolumab. Nivolumab is known for its effectiveness in treating cancers like metastatic melanoma, and the combination might enhance results. Previous studies using similar treatments have shown improved outcomes in patients. Overall, early evidence indicates that RP3, whether used alone or with Nivolumab, could be beneficial for advanced solid tumors. ^{5 6 7 8 9}

Who Is on the Research Team?

Shaheen Kumar, MD

Principal Investigator

Replimune Inc.

Are You a Good Fit for This Trial?

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.

History of viral infections according to the protocol

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04735978

NCT04735978 | Study of RP3 Monotherapy and ... This is a Phase 1, multicenter, open label, single agent dose escalation and combination treatment study of RP3 in adult participants with advanced solid ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.TPS2705

An open-label, multicenter, phase 1 study of RP3 as a ... A phase 2, open-label, multicenter study investigating efficacy and safety of RP3 oncolytic immunotherapy combined with other therapies in ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12482737/

Transforming cancer immunotherapy: integration of distinct ... When cancer progresses beyond the efficacy of dual immune checkpoint inhibitors, it can lead to disease advancement and poorer patient outcomes ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)00256-9/pdf

Clinical trial identification Preliminary data from phase 1 studies have demonstrated promising safety and efficacy of either agent in patients with solid tumors. This open-label ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT432418

or second-line systemic atezolizumab plus bevacizumab in ... Preclinical data have demonstrated improved distribution of oncolytic HSV within tumors in combination with Bev, supporting the clinical combination of RP3 with ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04735978

NCT04735978 | Study of RP3 Monotherapy and RP3 in ... This is a Phase 1, multicenter, open label, single agent dose escalation and combination treatment study of RP3 in adult participants with advanced solid ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.4_suppl.TPS623

An open-label, multicenter study investigating RP3 ... RP3 combined with anti-PD1 therapy has demonstrated clinical activity and safety in pts with various malignant solid tumors. This study will ...

8. trials.braintumor.org trials.braintumor.org/trials/NCT06887348

A Study to Assess the Long-term Safety Outcomes in Patients ... A Study to Assess the Long-term Safety Outcomes in Patients Previously Treated With RP1, RP2, or RP3 · Inclusion Criteria: · Exclusion Criteria: · Trial Details ...

9. ir.replimune.com ir.replimune.com/news-releases/news-release-details/replimune-announces-first-patient-dosed-rp3-phase-1-clinical

Replimune Announces First Patient Dosed with RP3 in a ... ... solid tumors. The clinical trial is primarily designed to assess safety and tolerability of RP3 and to determine the recommended Phase 2 dose.