RP1 + Nivolumab for Cancer

(IGNYTE Trial)

Recruiting at 54 trial locations

Overseen By Clinical Trials at Replimune

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Replimune Inc.

Must not be taking: Antivirals

Disqualifiers: Brain metastasis, Lung disease, Cardiovascular, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

340 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a modified virus (RP1) and an immune-boosting drug (nivolumab) in adults with advanced or treatment-resistant solid tumors. RP1 kills cancer cells and helps the immune system recognize them, while nivolumab enhances the immune response. Nivolumab has been approved for treating advanced melanoma, renal cell carcinoma, non-small cell lung cancer, and other malignancies.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on chronic anti-viral medications, you may not be eligible to participate.

What is known about the safety of Nivolumab and RP1 in humans?

Nivolumab, used in cancer treatment, has been studied in many trials and is generally safe, but can cause side effects like fatigue, rash, itching, diarrhea, nausea, and weakness. Serious side effects are less common, with low rates of severe low phosphate levels and low white blood cell counts. RP1, also known as vusolimogene oderparepvec, is less well-known, but combining it with Nivolumab is being studied for safety. ^{1 2 3 4 5}

How is the drug RP1 + Nivolumab unique for cancer treatment?

RP1 + Nivolumab is unique because it combines a virus-based therapy (RP1) with an immune checkpoint inhibitor (Nivolumab), which helps the immune system recognize and attack cancer cells more effectively. This combination aims to enhance the body's natural defenses against cancer, offering a novel approach compared to traditional treatments. ^{6 7 8 9 10}

What data supports the effectiveness of the drug Nivolumab in treating cancer?

Nivolumab has shown to improve overall survival and response rates in patients with advanced non-small cell lung cancer (NSCLC) compared to traditional chemotherapy, and it is better tolerated with a manageable side effect profile. ^{9 10 11 12 13}

Who Is on the Research Team?

Jeannie Hou, MD

Principal Investigator

Replimune Inc.

Are You a Good Fit for This Trial?

This trial is for adults with advanced skin cancer, melanoma, Lynch syndrome, or non-small cell lung cancer who have measurable disease and are in good physical condition (ECOG PS 0-1). Participants must have previously failed treatments including anti-PD1/PD-L1 therapy. They should be able to provide a tumor sample and not have a history of certain viral infections or heart diseases.

Inclusion Criteria

You are expected to live for at least 3 more months.

My skin cancer worsened on anti-PD1 treatment for 8+ weeks and I know my BRAF status.

I can provide a sample of my tumor for testing.

Exclusion Criteria

I have been treated with a virus-based cancer therapy before.

I have brain metastasis that is not being treated.

I have had viral infections as outlined in the study protocol.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Dose escalation phase for single agent RP1 to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D)

20 weeks

Dose Expansion

Expansion phase with a combination of RP1 and nivolumab to evaluate safety, tolerability, and preliminary efficacy

26 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

26 months

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab
• RP1

Trial Overview The study is testing RP1 alone and combined with nivolumab to find the safest dose that works best (MTD/RP2D) against solid tumors. It's an early-phase trial where everyone gets treatment: some just get RP1, others get it with nivolumab.

How Is the Trial Designed?

Group I: RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NSCLC Experimental Treatment 2 Interventions

Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non small cell lung cancer who have been previously treated with anti-PD1/PD-L1 therapy

Group II: RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NMSC Experimental Treatment 2 Interventions

Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non-melanoma skin cancer who have been previously treated with anti-PD1/PD-L1 therapy

Group III: RP1(IT) and nivolumab (IV) in anti-PD1 Failed Cutaneous Melanoma Experimental Treatment 2 Interventions

Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with cutaneous melanoma who have been previously treated with anti-PD1 therapy

Group IV: RP1 (IT) and nivolumab (IV) in melanoma Experimental Treatment 2 Interventions

Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with melanoma

Group V: RP1 (IT) and nivolumab (IV) in NMSC Experimental Treatment 2 Interventions

Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non-melanoma skin cancer

Group VI: RP1 (IT) and nivolumab (IV) in MSI-H/dMMR solid tumors Experimental Treatment 2 Interventions

Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with MSI-H or dMMR solid tumors

Group VII: Dose expansion of RP1 and nivolumab (IV) in superficial tumors Experimental Treatment 2 Interventions

Doses of RP1 (IT) in superficial tumors with nivolumab (IV)

Group VIII: Dose expansion of RP1 and nivolumab (IV) in deep/visceral tumors Experimental Treatment 2 Interventions

Doses of RP1 (IT) in deep/visceral tumors with nivolumab (IV)

Group IX: Dose escalation of RP1 by intratumoral (IT) injection in superficial tumors Experimental Treatment 1 Intervention

Dose escalation of RP1 alone in 3 cohorts with IT injections in superficial tumors

Group X: Dose escalation of RP1 by intratumoral (IT) injection in deep/visceral tumors Experimental Treatment 1 Intervention

Dose escalation of RP1 alone in 3 cohorts with IT injections in deep/visceral tumors

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

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

Nivolumab plus ipilimumab showed durable and long-term efficacy in treating advanced non-small cell lung cancer (NSCLC) compared to chemotherapy, regardless of tumor PD-L1 expression levels.

These findings are based on updated results from part 1 of the phase 3 CheckMate 227 trial, indicating that this combination therapy could be a more effective frontline treatment option for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab/Ipilimumab Combo Yields Durable Efficacy in Advanced NSCLC. Kahl, KL.[2021]

Nivolumab, an immune checkpoint inhibitor, significantly improves overall survival and progression-free survival in patients with advanced stage squamous cell non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CHECKMATE 017 study.

The safety and tolerability of nivolumab are favorable, and interestingly, the expression of the PD-L1 ligand does not predict treatment outcomes, suggesting that other factors may influence the effectiveness of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab in the treatment of metastatic squamous non-small cell lung cancer: a review of the evidence. Lim, JS., Soo, RA.[2018]

Nivolumab (Opdivo) significantly improves overall survival and response rates in previously-treated patients with advanced nonsquamous non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CheckMate 057 trial.

Nivolumab has a manageable adverse event profile and is better tolerated than docetaxel, making it a valuable treatment option for patients who have progressed after chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. Keating, GM.[2018]

Nivolumab, an immune checkpoint inhibitor, significantly improved overall survival and progression-free survival compared to docetaxel in patients with advanced squamous non-small cell lung cancer (NSCLC) in the CheckMate 017 trial.

Nivolumab was better tolerated than docetaxel, with manageable adverse effects, making it a promising treatment option for patients who have already undergone chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. Keating, GM.[2022]

Nivolumab treatment resulted in an increased overall survival rate of 7.5 months compared to 5.1 months for the control group, indicating its efficacy in extending life for patients.

Patients receiving nivolumab also reported a better quality of life, suggesting that the treatment not only prolongs survival but also improves the well-being of those undergoing therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab for recurrent squamous-cell carcinoma of the head and neck. [2018]

Nivolumab and pembrolizumab, both PD-1 inhibitors, show a lower risk of severe treatment-related adverse effects (AEs) compared to standard care, with a relative risk of 0.39 for grade 3/4 AEs based on a meta-analysis of 9 trials involving 5,353 patients.

While these therapies are generally well tolerated, they are associated with a significantly increased risk of thyroid dysfunction (hyperthyroidism and hypothyroidism) and skin conditions like pruritus and vitiligo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity profile of approved anti-PD-1 monoclonal antibodies in solid tumors: a systematic review and meta-analysis of randomized clinical trials. Costa, R., Carneiro, BA., Agulnik, M., et al.[2022]

Nivolumab, an immune checkpoint inhibitor, shows a low rate of severe adverse effects (grade ≥3 AEs at 12%) and a very low mortality rate (0.25%), indicating it is a relatively safe treatment option for cancer patients.

In terms of efficacy, nivolumab demonstrates better treatment responses and survival rates compared to traditional chemotherapy, with a 1-year overall survival rate of 52% and a significantly higher objective response rate (ORR) of 26%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of nivolumab in the treatment of cancers: A meta-analysis of 27 prospective clinical trials. Tie, Y., Ma, X., Zhu, C., et al.[2022]

In a study of 53 patients with metastatic renal cell carcinoma treated with nivolumab, those who experienced immune-related adverse events (irAEs) had significantly better overall survival compared to those without irAEs, indicating a potential link between irAEs and treatment efficacy.

The study found that a lower platelet-to-lymphocyte ratio before treatment was a risk factor associated with the development of irAEs, suggesting that this ratio could be a useful predictor for monitoring patient responses to nivolumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association Between Immune-related Adverse Events and Clinical Outcome Following Nivolumab Treatment in Patients With Metastatic Renal Cell Carcinoma. Kobayashi, K., Iikura, Y., Hiraide, M., et al.[2021]

In a study of 46 patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab, 72% experienced immune-related adverse events (irAEs), which were linked to significantly longer progression-free survival (PFS) compared to those without irAEs.

While irAE development was an independent predictor of longer PFS, it did not affect overall survival (OS), suggesting that irAEs could serve as a useful prognostic marker for treatment outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic impact of immune-related adverse events in metastatic renal cell carcinoma treated with nivolumab plus ipilimumab. Ikeda, T., Ishihara, H., Nemoto, Y., et al.[2022]

Nivolumab, an immune checkpoint inhibitor for metastatic melanoma, can cause immune-related adverse events (irAEs) such as colitis, which were observed in two patients after treatment.

The development of these irAEs is linked to a Th1 dominant immune response, and serum levels of C-reactive protein (CRP) and interleukin-6 (IL-6) may serve as potential biomarkers to monitor and manage these adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe colitis after PD-1 blockade with nivolumab in advanced melanoma patients: potential role of Th1-dominant immune response in immune-related adverse events: two case reports. Yoshino, K., Nakayama, T., Ito, A., et al.[2020]

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]

Nivolumab is a promising immunotherapy for advanced renal cell carcinoma (aRCC) that works differently than traditional therapies targeting blood vessel growth, offering a new treatment option for patients.

The commentary reviews clinical experiences and practical considerations for using nivolumab, highlighting its unique response patterns and safety profiles compared to conventional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab treatment for advanced renal cell carcinoma: Considerations for clinical practice. Joseph, RW., Chatta, G., Vaishampayan, U.[2019]

Nivolumab, an anti-PD-1 antibody, was administered to a 63-year-old female patient with metastatic melanoma after renal transplantation, highlighting the potential for anti-tumor activity in high-risk patients, despite the challenges of concurrent immunosuppression.

The patient experienced acute renal allograft rejection and renal failure shortly after starting nivolumab, indicating significant risks associated with this treatment in transplant recipients, but she later showed a positive clinical response after re-challenging with nivolumab while on hemodialysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. Ong, M., Ibrahim, AM., Bourassa-Blanchette, S., et al.[2023]

Citations

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

Nivolumab/Ipilimumab Combo Yields Durable Efficacy in Advanced NSCLC. [2021]

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

Nivolumab in the treatment of metastatic squamous non-small cell lung cancer: a review of the evidence. [2018]

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

Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. [2018]

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

Nivolumab: a review in advanced squamous non-small cell lung cancer. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Nivolumab for recurrent squamous-cell carcinoma of the head and neck. [2018]

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

Toxicity profile of approved anti-PD-1 monoclonal antibodies in solid tumors: a systematic review and meta-analysis of randomized clinical trials. [2022]

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

Safety and efficacy of nivolumab in the treatment of cancers: A meta-analysis of 27 prospective clinical trials. [2022]

8. Greece pubmed.ncbi.nlm.nih.gov

Association Between Immune-related Adverse Events and Clinical Outcome Following Nivolumab Treatment in Patients With Metastatic Renal Cell Carcinoma. [2021]

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

Prognostic impact of immune-related adverse events in metastatic renal cell carcinoma treated with nivolumab plus ipilimumab. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Severe colitis after PD-1 blockade with nivolumab in advanced melanoma patients: potential role of Th1-dominant immune response in immune-related adverse events: two case reports. [2020]

11. England pubmed.ncbi.nlm.nih.gov

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

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

Nivolumab treatment for advanced renal cell carcinoma: Considerations for clinical practice. [2019]

13. England pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. [2023]