What side effects are associated with this type of intervention?

Common treatments for Non-Small Cell Lung Cancer (NSCLC) include PD-1 inhibitors like Pembrolizumab and investigational therapies such as VSV-IFNβ-NIS. Pembrolizumab can cause side effects like fatigue, rash, diarrhea, and severe immune-related adverse events including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. Oncolytic virus therapies may lead to flu-like symptoms, injection site reactions, and immune-related adverse events. When combined with chemotherapy, these treatments can increase the risk of severe side effects such as neutropenia, anemia, and febrile neutropenia.

What prior FDA approvals exist?

Pembrolizumab, a PD-1 inhibitor, has been FDA approved for the treatment of NSCLC, particularly in patients with high PD-L1 expression (≥50%). Other similar immune checkpoint inhibitors include Nivolumab and Atezolizumab, which have also received FDA approval for NSCLC. Nivolumab is approved for previously treated advanced esophageal squamous cell carcinoma, and Atezolizumab is approved for front-line treatment of NSCLC with high PD-L1 expression. While there is limited information on FDA approvals for oncolytic viruses with interferon-beta for NSCLC, the use of immune checkpoint inhibitors like Pembrolizumab and Atezolizumab represents a significant advancement in the treatment of this disease.

What other types of research exist?

Promising novel alternatives for NSCLC treatment in 2024 include: 1) Durvalumab plus Tremelimumab and chemotherapy, which has shown improved progression-free survival in metastatic NSCLC. 2) Nivolumab combined with Ipilimumab, which is being explored for its potential to enhance immune response. 3) JAK/STAT inhibitors like Ruxolitinib combined with virotherapy, which have shown potential in preclinical models. These alternatives offer different mechanisms of action and combination strategies that may provide benefits for NSCLC patients.

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Checkpoint Inhibitor

Combination Immunotherapy + VSV-IFNβ-NIS for Solid Tumors

Phase 1 & 2

Recruiting

Led By Alex Adjei, MD, PhD

Research Sponsored by Vyriad, Inc.

Eligibility Criteria Checklist

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

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 6 months

Awards & highlights

All Individual Drugs Already Approved

No Placebo-Only Group

Summary

This trial tests a combination of a virus-based therapy and an immune-boosting drug for patients with hard-to-treat cancers. The treatment works by making cancer cells more visible to the immune system and keeping the immune system active against them.

Who is the study for?

This trial is for adults with advanced or metastatic non-small cell lung cancer (NSCLC) or neuroendocrine carcinoma (NEC) that worsened on PD-1/PD-L1 inhibitor therapy. They should have a life expectancy over 3 months, no active brain cancer involvement, good organ function, and be willing to provide tissue samples. Pregnant women, those with certain autoimmune diseases or unresolved treatment toxicities, and individuals with other serious health risks are excluded.

What is being tested?

The study tests different doses of VSV-IFNβ-NIS combined with pembrolizumab to find the safest and most effective dose for treating solid tumors including NSCLC and NEC. It starts by testing safety in small groups using a '3+3 design' before expanding to more patients once the optimal dose is found.

What are the potential side effects?

Potential side effects may include typical reactions from immunotherapy like inflammation in various organs, flu-like symptoms due to the viral component of VSV-IFNβ-NIS, fatigue, possible infusion-related reactions from pembrolizumab administration, as well as increased risk of infections.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 6 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~6 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 6 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

Expansion arms: Overall response rate (ORR)

Safety run-in arm: Number of participants with treatment related adverse events (NCI CTCAE; Version 4.03)

Secondary study objectives

Adverse events

Disease Control Rate (DCR)

Duration of response

+2 more

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

No Placebo-Only Group

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

Trial Design

5Treatment groups

Experimental Treatment

Group I: Safety Run-in Dose Level 2Experimental Treatment2 Interventions

Patients with pembrolizumab refractory Neuroendocrine Carcinoma (NEC) or non small cell lung cancer (NSCLC) will receive a single IV dose of 1.0e11 TCID50 VSV-IFNβ-NIS in combination with Pembrolizumab at standard labeled dose administered on day 8, then every 21 days, up to 2 years.

Group II: Safety Run-in Dose Level 1Experimental Treatment2 Interventions

Patients with pembrolizumab refractory solid tumors will receive a single IV dose of 5e10 TCID50 VSV-IFNβ-NIS in combination with Pembrolizumab at standard labeled dose administered on day 1, then every 21 days, up to 2 years.

Group III: Expansion Part DExperimental Treatment2 Interventions

Patients with non small cell lung cancer (NSCLC) or Neuroendocrine Carcinoma (NEC) will receive a single IV dose of VSV-IFNβ-NIS on Day 4 in combination with ipilumumab + nivolumab at standard labeled dose administered on Day 1 then every 21 days up to 2 years.

Group IV: Expansion NSCLC armExperimental Treatment2 Interventions

Patients with pembrolizumab refractory non small cell lung cancer (NSCLC) will receive a single IV dose of 1.0e11 TCID50 VSV-IFNβ-NIS in combination with Pembrolizumab at standard labeled dose administered on day 8, then every 21 days, up to 2 years.

Group V: Expansion NECExperimental Treatment2 Interventions

Patients with pembrolizumab refractory Neuroendocrine Carcinoma (NEC) will receive a single IV dose of 1.0e11 TCID50 VSV-IFNβ-NIS in combination with Pembrolizumab at standard labeled dose administered on day 8, then every 21 days, up to 2 years.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

VSV-IFNβ-NIS

2017

Completed Phase 1

~80

Pembrolizumab

FDA approved

Do I qualify?Apply below to find out

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

Common treatments for Non-Small Cell Lung Cancer (NSCLC) include oncolytic viruses like VSV-IFNβ-NIS and immune checkpoint inhibitors like Pembrolizumab. VSV-IFNβ-NIS works by selectively infecting and killing cancer cells, enhancing the immune response with interferon-beta, and allowing for imaging to track the virus. Pembrolizumab, a PD-1 inhibitor, blocks the PD-1 pathway that cancer cells use to evade immune detection, thereby reactivating T-cells to attack the cancer. These treatments are significant for NSCLC patients as they provide targeted therapies that enhance the body's immune response against cancer, potentially improving outcomes and reducing side effects compared to traditional treatments.

Efficacy and Safety of Sintilimab Plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC: a Randomized, Double-Blind, Phase 3 Study (Oncology pRogram by InnovENT anti-PD-1-11).