RP1 + Nivolumab for Cancer
(IGNYTE Trial)
Recruiting in Palo Alto (17 mi)
+54 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Replimune Inc.
Must not be taking: Antivirals
Disqualifiers: Brain metastasis, Lung disease, Cardiovascular, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
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 data supports the effectiveness of the drug Nivolumab in treating cancer?
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.678910
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.24111213
Research Team
JH
Jeannie Hou, MD
Principal Investigator
Replimune Inc.
Eligibility Criteria
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.
See 6 more
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.
See 5 more
Trial Timeline
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
Treatment Details
Interventions
- Nivolumab (Checkpoint Inhibitor)
- RP1 (Virus Therapy)
Trial OverviewThe 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.
Participant Groups
10Treatment groups
Experimental Treatment
Group I: RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NSCLCExperimental Treatment2 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 NMSCExperimental Treatment2 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 MelanomaExperimental Treatment2 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 melanomaExperimental Treatment2 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 NMSCExperimental Treatment2 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 tumorsExperimental Treatment2 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 tumorsExperimental Treatment2 Interventions
Doses of RP1 (IT) in superficial tumors with nivolumab (IV)
Group VIII: Dose expansion of RP1 and nivolumab (IV) in deep/visceral tumorsExperimental Treatment2 Interventions
Doses of RP1 (IT) in deep/visceral tumors with nivolumab (IV)
Group IX: Dose escalation of RP1 by intratumoral (IT) injection in superficial tumorsExperimental Treatment1 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 tumorsExperimental Treatment1 Intervention
Dose escalation of RP1 alone in 3 cohorts with IT injections in deep/visceral tumors
Nivolumab is already approved in Canada, Switzerland for the following indications:
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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Penn State Hershey Medical CenterHershey, PA
University of Southern CaliforniLos Angeles, CA
Seattle Cancer Care Alliance- University of WashingtonSeattle, WA
Banner MD Anderson Cancer CenterGilbert, AZ
More Trial Locations
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Who Is Running the Clinical Trial?
Replimune Inc.
Lead Sponsor
Trials
16
Patients Recruited
1,700+
Bristol-Myers Squibb
Industry Sponsor
Trials
2731
Patients Recruited
4,127,000+
Headquarters
New York City, USA
Known For
Oncology & Cardiovascular
Top Products
Eliquis, Opdivo, Revlimid, Orencia
Findings from Research
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Nivolumab/Ipilimumab Combo Yields Durable Efficacy in Advanced NSCLC.Kahl, KL.[2021]
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]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer.Keating, GM.[2018]
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]
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]
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]
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]
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]
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]
References
Nivolumab/Ipilimumab Combo Yields Durable Efficacy in Advanced NSCLC. [2021]
Nivolumab in the treatment of metastatic squamous non-small cell lung cancer: a review of the evidence. [2018]
Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. [2018]
Nivolumab: a review in advanced squamous non-small cell lung cancer. [2022]
Nivolumab for recurrent squamous-cell carcinoma of the head and neck. [2018]
Toxicity profile of approved anti-PD-1 monoclonal antibodies in solid tumors: a systematic review and meta-analysis of randomized clinical trials. [2022]
Safety and efficacy of nivolumab in the treatment of cancers: A meta-analysis of 27 prospective clinical trials. [2022]
Association Between Immune-related Adverse Events and Clinical Outcome Following Nivolumab Treatment in Patients With Metastatic Renal Cell Carcinoma. [2021]
Prognostic impact of immune-related adverse events in metastatic renal cell carcinoma treated with nivolumab plus ipilimumab. [2022]
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]
Pharmacokinetics, pharmacodynamics and clinical efficacy of nivolumab in the treatment of metastatic renal cell carcinoma. [2018]
Nivolumab treatment for advanced renal cell carcinoma: Considerations for clinical practice. [2019]
Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. [2023]