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?

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. ^{1 2 3 4 5}

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. ^{6 7 8 9 10}

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. ^{2 4 11 12 13}

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.

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.

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 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.

Participant Groups

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Penn State Hershey Medical Center Hershey, PA

University of Southern Californi Los Angeles, CA

Seattle Cancer Care Alliance- University of Washington Seattle, WA

Banner MD Anderson Cancer Center Gilbert, AZ

More Trial Locations

Who Is Running the Clinical Trial?

Replimune Inc. Lead Sponsor

Bristol-Myers Squibb Industry Sponsor

References

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

Nivolumab/Ipilimumab Combo Yields Durable Efficacy in Advanced NSCLC. [2021] Frontline treatment with nivolumab (Opdivo) plus ipilimumab (Yervoy) induced durable and long-term efficacy, compared with chemotherapy, in patients with advanced non-small cell lung cancer (NSCLC) and tumor PD-L1 expression greater than 1% or less than 1%, according to updated results from part 1 of the phase 3 CheckMate 227 (NCT02477826)trial presented at the 2020 American Society of Clinical Oncology Virtual Scientific Program.

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] Progress in the treatment of patients with advanced stage squamous cell non-small cell lung cancer (NSCLC) has been limited. An improvement in the understanding of tumor immunosurveillance has resulted in the development of the immune checkpoint inhibitors such as nivolumab. Nivolumab (Opdivo(®)), a human immunoglobulin (Ig)G4 anti-programmed death (PD)-1 monoclonal antibody, was the first PD-1 inhibitor approved in the treatment of patients with advanced stage squamous cell NSCLC following platinum-based chemotherapy. CHECKMATE 017, a randomized phase III study of second-line nivolumab versus docetaxel, significantly improved overall survival (OS), progression-free survival (PFS), patient reported outcomes and the safety and tolerability favored patients treated with nivolumab. The ligand (PD-L1) expression did not predict for outcome. In this paper, we review the role of nivolumab in the treatment of NSCLC with particular attention on recent studies, ongoing combination studies, toxicity profile, current and potential predictive biomarkers.

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

Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. [2018] The programmed death (PD)-1 immune checkpoint inhibitor nivolumab (Opdivo(®)) is approved in the USA for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) who have progression on or after platinum-based chemotherapy and in the EU for the treatment of adults with locally advanced or metastatic NSCLC after prior chemotherapy. In previously-treated patients with advanced nonsquamous NSCLC, overall survival was significantly prolonged and the overall response rate was significantly higher in patients who received intravenous nivolumab 3 mg/kg every 2 weeks versus intravenous docetaxel in the pivotal CheckMate 057 trial. Progression-free survival did not significantly differ between patients receiving nivolumab and those receiving docetaxel. Intravenous nivolumab had a manageable adverse event profile (including immune-mediated adverse events) and was better tolerated than docetaxel in the CheckMate 057 trial. Thus, nivolumab is an important new option for use in previously-treated patients with advanced nonsquamous NSCLC.

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

Nivolumab: a review in advanced squamous non-small cell lung cancer. [2022] Nivolumab (Opdivo(®); Nivolumab BMS™) was the first programmed death (PD)-1 immune checkpoint inhibitor to be approved for use in advanced, squamous non-small cell lung cancer (NSCLC) following prior chemotherapy. In the pivotal CheckMate 017 trial, intravenous nivolumab 3 mg/kg every 2 weeks was associated with significantly better overall survival and progression-free survival and a significantly higher overall response rate than intravenous docetaxel in the second-line treatment of advanced, squamous NSCLC. Nivolumab was also better tolerated than docetaxel in CheckMate 017, and its adverse event profile (which included immune-mediated adverse events) was manageable. In conclusion, nivolumab represents an important advance in previously-treated, advanced, squamous NSCLC.

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

Nivolumab for recurrent squamous-cell carcinoma of the head and neck. [2018] Increased overall survival with nivolumab albeit only 7.5 months vs 5.1 months, and a better quality of life.

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] Nivolumab and pembrolizumab are antibodies against the programmed-death-receptor- 1 (PD-1) which are associated with distinct immune related adverse effects (AEs). This meta-analysis of randomized clinical trials aims to summarize current knowledge regarding the toxicity profile of these agents.

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] Immune checkpoint inhibition therapy has benefited people and shown powerful anti-tumor activity during the past several years. Nivolumab, a fully human IgG4 monoclonal antibody against PD-1, is a widely studied immune checkpoint inhibitor for the treatment of cancers. To assess the safety and efficacy of nivolumab, 27 clinical trials on nivolumab were analyzed. Results showed that the summary risks of all grade adverse effects (AEs) and grade ≥3 AEs were 0.65 and 0.12. The rate of nivolumab-related death was 0.25%. The most common any grade AEs were fatigue (25.1%), rush (13.0%), pruritus (12.5%), diarrhea (12.1%), nausea (11.8%) and asthenia (10.4%). The most common grade ≥3 AEs were hypophosphatemia (only 2.3%) and lymphopenia (only 2.1%). The pooled objective response rate (ORR), 6-month progression-free survival (PFS) rate and 1-year overall survival (OS) rate were 0.26, 0.40 and 0.52, respectively. The odds ratio of ORR between PD-L1 positive and negative was 2.34 (95% CI 1.77-3.10, p

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] Immune-related adverse events (irAEs) are associated with the efficacy of immune-checkpoint inhibitors in patients with melanoma and non-small cell lung cancer. We therefore evaluated the relationship between irAEs and nivolumab efficacy against metastatic renal cell carcinoma.

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] Evidence regarding the prognostic impact of immune-related adverse events (irAEs) remains limited in patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab plus ipilimumab as a first-line systemic therapy. Thus, we investigated the association between irAE development and oncological outcomes during nivolumab plus ipilimumab therapy.

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] Nivolumab is an immune checkpoint inhibitor specific to the programmed death 1 (PD-1) receptor. Nivolumab has shown clinical responses in many malignancies. Although immune-related adverse events (irAEs) associated with nivolumab are largely tolerable, severe irAEs have occurred in some patients. However, the mechanisms underlying the development of irAEs are not fully clarified.

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

Pharmacokinetics, pharmacodynamics and clinical efficacy of nivolumab in the treatment of metastatic renal cell carcinoma. [2018] Nivolumab is a recombinant, humanized monoclonal antibody that binds PD-1. The binding of PD-1 with PD-L1, expressed on antigen-presenting cells and tumor cells, suppresses the ability of T-lymphocytes to recognize and destroy tumor cells. Nivolumab reverts this inhibitory signal and has led to a significant prolongation of overall survival in patients with metastatic renal cell carcinoma (RCC).

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

Nivolumab treatment for advanced renal cell carcinoma: Considerations for clinical practice. [2019] Nivolumab is an important new therapy option for patients with advanced renal cell carcinoma, and has a different mechanism of action compared with vascular endothelial growth factor -targeted therapies. It is a programmed death 1 immune checkpoint inhibitor antibody with response patterns, efficacy, and safety profiles that differ from those of conventional antiangiogenic or mammalian target of rapamycin inhibition therapy.

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

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. [2023] Nivolumab (Opdivo™) is a novel IgG4 subclass programmed death-1 (PD-1) inhibiting antibody that has demonstrated breakthrough-designation anti-tumor activity. To date, clinical trials of nivolumab and other checkpoint inhibitors have generally excluded patients with solid organ transplantation and patients with concurrent immunosuppression. However, organ transplant recipients are at high-risk of development of malignancy as a result of suppressed immune surveillance of cancer.