Nous-209 Vaccine for Metastatic Cancer

Recruiting at 50 trial locations

Overseen By Juan De Alvaro, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Nouscom SRL

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

Compensation: Varies

Number of Visits: Unknown

115 Participants Needed

Trial Summary

What is the purpose of this trial?

Ref: Protocol v9.0, dated 7Nov2023. NOUS-209-01 is a multicenter, open-label, multiple cohorts, clinical study, designed to evaluate safety, tolerability, and immunogenicity, and to detect any preliminary evidence of anti-tumor activity of Nous-209 genetic polyvalent vaccine plus pembrolizumab combination therapy in adult subjects with unresectable or metastatic deficient mismatch repair (dMMR) or MSI-H CRC, gastric, or gastro-esophageal junction (G-E junction) tumors. Nous-209 is based on a heterologous prime/boost regimen composed of the Great Ape Adenovirus GAd20-209-FSP used for priming and Modified Vaccinia virus Ankara MVA-209-FSP used for boosting. The Phase I portion of the study is a first-in-human (FIH) clinical study with a primary objective to elucidate the safety and tolerability of Nous-209 in addition to establishing the recommended Phase 2 dose (RP2D), whereas the Phase II was introduced to assess efficacy as the primary objective.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that participants should not be on certain immunosuppressive therapies or have received recent live-virus vaccinations. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the Nous-209 treatment for metastatic cancer?

Research on Nous-209, a vaccine for tumors with microsatellite instability (MSI), shows it can trigger strong immune responses in mice and activate human immune cells in lab tests. This suggests it might help treat and prevent MSI tumors, which are a type of cancer with specific genetic changes. ^{1 2 3 4 5}

How is the Nous-209 vaccine different from other treatments for metastatic cancer?

The Nous-209 vaccine is unique because it is designed to stimulate the immune system to target specific cancer cells, potentially offering a personalized approach to treating metastatic cancer. Unlike traditional treatments, it may work by enhancing the body's natural defenses to fight cancer. ^{3 6 7 8 9}

Research Team

Sven Gogov, MD

Principal Investigator

Nouscom SRL

Eligibility Criteria

Adults over 18 with certain advanced solid tumors (like colorectal, gastric, or gastro-esophageal junction cancers) that are microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). They must not have used PD-1/PD-L1 inhibitors before and should be in a condition where they can handle biopsies. Participants need to have an acceptable performance status, meet specific blood criteria, use effective contraception if of childbearing potential, and understand the study's consent form.

Inclusion Criteria

I can carry out all my usual activities without help.

I am using effective birth control methods.

I agree to have two biopsies if it's safe for me.

Exclusion Criteria

My cancer has spread to my brain or its coverings.

You are pregnant or currently breastfeeding.

I do not have chronic illnesses that would affect my participation in the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Dose escalation and expansion cohort with Nous-209 vaccine plus pembrolizumab combination therapy

26 weeks

Multiple visits for prime and boost vaccinations

Phase I Extended Follow-up

Extended follow-up to monitor long-term safety and efficacy

84 weeks

Phase II Treatment

Expansion at RP2D of Nous-209 vaccine plus pembrolizumab combination therapy

12-18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Treatment Details

Interventions

• Nous-209

Trial Overview The trial is testing Nous-209 genetic vaccine combined with pembrolizumab for treating MSI-H/dMMR tumors. It uses two types of viruses for priming and boosting the immune system. The first phase focuses on safety and finding the right dose; the second phase looks at how well it works against cancer.

Participant Groups

Group I: Cohort D - Expansion cohort Phase II Experimental Treatment 3 Interventions

Phase II. Subjects with locally advanced unresectable or metastatic, microsatellite instability high (MSI-H) or dMMR CRC who have had radiographic progression (PD) after having a best response of stable disease (SD) or better on/after anti-PD1 treatment. Nous-209 vaccine plus Keytruda® (pembrolizumab) combination therapy.

Group II: Cohort C - Expansion cohort Phase II Experimental Treatment 3 Interventions

Phase II. Subjects with locally advanced unresectable or metastatic, microsatellite instability high (MSI-H) or dMMR CRC who are eligible for anti-PD-1 1st line of treatment. Subjects will be randomized with an allocation ratio 2:1 to Nous-209 vaccine plus Keytruda® (pembrolizumab) combination therapy versus pembrolizumab monotherapy.

Group III: Cohort B - Expansion Cohort Phase I Experimental Treatment 3 Interventions

Phase I. Part 1. Expansion cohort at RP2D. Subjects treated with RP2D dose of GAd20-209-FSP prime and MVA-209-FSP boosts, in combination with pembrolizumab. Phase I. Part 2 - Extended Follow-up from week 27 to week 110. Subjects with unresectable or metastatic dMMR or MSI-H CRC, gastric, or G-E junction tumors.

Group IV: Cohort A - Dose-escalation Experimental Treatment 3 Interventions

Phase I. Part 1. Dose escalation cohort. Subjects treated with low dose or with high dose of GAd20-209-FSP prime and MVA-209-FSP boosts to define the RP2D, in combination with pembrolizumab. Phase I. Part 2 - Extended Follow-up from week 27 to week 110. Subjects with unresectable or metastatic deficient mismatch repair (dMMR) or MSI-H CRC, gastric, or gastro-esophageal junction (G-E junction) tumors.

Who Is Running the Clinical Trial?

Nouscom SRL

Lead Sponsor

Trials

2

Recruited

120+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

The study developed an 'off-the-shelf' neoantigen-based vaccine called Nous-209, targeting shared frameshift peptides (FSPs) from 320 microsatellite instability (MSI) tumor biopsies, which could potentially treat and prevent MSI tumors.

Immunogenicity tests in mice showed that Nous-209 effectively induced strong CD8 and CD4 T-cell responses, indicating its potential to elicit a robust immune response against MSI tumors in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Genetic Vaccine Encoding Shared Cancer Neoantigens to Treat Tumors with Microsatellite Instability. Leoni, G., D'Alise, AM., Cotugno, G., et al.[2021]

Breast cancer vaccines have been developed to enhance immune responses against the disease, but large clinical trials have not yet shown significant improvements in progression-free or overall survival rates.

Current research is focusing on combining breast cancer vaccines with other therapies and exploring their use in preventing relapse or even the initial development of breast cancer, particularly in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Breast cancer vaccines for treatment and prevention. Disis, ML., Cecil, DL.[2022]

References

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

A Genetic Vaccine Encoding Shared Cancer Neoantigens to Treat Tumors with Microsatellite Instability. [2021]

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

A clinical trials outcome paradox: should survival prevail in the absence of clinical benefit? [2010]

3. Switzerland pubmed.ncbi.nlm.nih.gov

The role of sipuleucel-T in therapy for castration-resistant prostate cancer: a critical analysis of the literature. [2021]

4. China pubmed.ncbi.nlm.nih.gov

Clinical benefit and safety associated with mRNA vaccines for advanced solid tumors: A meta-analysis. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Breast cancer vaccines for treatment and prevention. [2022]

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

Transcription factor Fos-related antigen 1 is an effective target for a breast cancer vaccine. [2018]

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

Efficacy for lung metastasis induced by the allogeneic bEnd3 vaccine in mice. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Double-blind, placebo-controlled first in human study to investigate an oral vaccine aimed to elicit an immune reaction against the VEGF-Receptor 2 in patients with stage IV and locally advanced pancreatic cancer. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Endoglin (CD105) is a target for an oral DNA vaccine against breast cancer. [2022]