What side effects are associated with this type of intervention?

Common treatments for NSCLC, particularly those involving PD-1 inhibitors like Nivolumab, often result in side effects such as fatigue, rash, diarrhea, and pneumonitis. Severe immune-related adverse events can include colitis, hepatitis, endocrinopathies, and nephritis. Oncolytic virus therapies, while less commonly detailed, may cause flu-like symptoms, injection site reactions, and potential immune responses. It is crucial for patients to discuss these potential side effects with their healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

The FDA has approved several immunotherapies for the treatment of Non-Small Cell Lung Cancer (NSCLC). Nivolumab, a PD-1 inhibitor, has been approved for patients with metastatic NSCLC whose disease progressed during or following platinum-based chemotherapy. Pembrolizumab, another PD-1 inhibitor, is approved for first-line treatment of patients with NSCLC with PD-L1 expression of ≥50% and no EGFR or ALK mutations. Atezolizumab, a PD-L1 inhibitor, is also approved for metastatic NSCLC following progression on platinum-based chemotherapy. These approvals highlight the role of immune checkpoint inhibitors in the management of NSCLC.

What other types of research exist?

Promising alternatives to RP1 and Nivolumab for NSCLC patients include: 1) Pembrolizumab plus chemotherapy, which has shown improved PFS and ORR in various trials. 2) Durvalumab plus tremelimumab, particularly for patients with high tumor mutational burden (TMB), which has demonstrated improved OS in post-hoc analyses. 3) Tislelizumab combined with chemotherapy, which has shown efficacy in squamous cell NSCLC. 4) Sintilimab with chemotherapy, which has improved PFS in both squamous and nonsquamous carcinoma and is under FDA review.

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Checkpoint Inhibitor

RP1 + Nivolumab for Cancer (IGNYTE Trial)

Phase 2

Recruiting

Research Sponsored by Replimune Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Subjects with anti-PD1 failed cutaneous melanoma: has confirmed progressive disease while on anti-PD1 treatment for at least 8 weeks and documented BRAF mutation status

Have provided a former tumor pathology specimen or be willing to supply a new tumor sample from a biopsy

Must not have

Prior treatment with an oncolytic therapy

Uncontrolled/untreated brain metastasis

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 26 months

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include typical immune-related reactions like inflammation in various organs due to immune system activation by these therapies. There may also be injection site reactions from RP1 and general symptoms such as fatigue.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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I can provide a sample of my tumor for testing.

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I have at least one tumor that can be measured and injected.

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My NSCLC worsened despite treatment with anti-PD1/PD-L1 therapy.

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My tumor is MSI-H/dMMR and has not improved with specific immune therapy.

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I have advanced skin cancer not treatable by surgery and progressed after 8 weeks of anti-PD1/PD-L1 treatment.

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I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I have brain metastasis that is not being treated.

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I have a history of lung scarring or fibrosis.

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I have a history of serious heart problems.

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I regularly take anti-viral medication.

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I have had lung inflammation not caused by an infection.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 26 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~26 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 26 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RP1

Percentage of adverse events (AEs)

Percentage of dose limiting toxicities (DLTs)

+2 more

Secondary study objectives

Median duration of response

Median overall survival

Median progression-free survival

+3 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

nivolumab

2016

Completed Phase 3

~4960

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Non-Small Cell Lung Cancer (NSCLC) include targeted therapies, immunotherapies, and chemotherapy. Oncolytic viruses like RP1 work by selectively infecting and killing cancer cells while stimulating an anti-tumor immune response. Nivolumab, a PD-1 inhibitor, blocks the programmed cell death protein 1 (PD-1) pathway, which cancer cells exploit to evade immune detection. By inhibiting this pathway, Nivolumab enhances the body's immune response against cancer cells. These mechanisms are crucial for NSCLC patients as they offer targeted approaches that can improve survival rates and quality of life by effectively managing the disease with potentially fewer side effects compared to traditional chemotherapy.

Emerging therapeutic agents for lung cancer.