Nous-209 Vaccine for Metastatic Cancer

Not currently recruiting at 56 trial locations

Overseen By Juan De Alvaro, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Nouscom SRL

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Immunodeficiency, CNS metastases, Pneumonitis, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new vaccine, Nous-209, combined with Keytruda® (pembrolizumab), for treating certain advanced cancers that cannot be surgically removed, such as specific types of colon, gastric, or gastro-esophageal junction tumors. The main goal is to determine if this combination is safe and can trigger the body's immune response to fight the cancer. Individuals diagnosed with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) cancers, who have not previously received similar treatments, might be suitable candidates. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the Nous-209 vaccine, when combined with pembrolizumab, is safe and well-tolerated. Patients who received this combination did not encounter major safety issues. The treatment effectively activated the immune system and showed promising results against tumors.

These studies involved patients with specific types of cancer, such as colorectal and gastric cancers, which have a particular genetic marker (MSI-H or dMMR). While current data suggests the treatment is safe, prospective trial participants should consult their doctor about potential risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this study treatment?

Researchers are excited about the Nous-209 vaccine because it represents a novel approach to treating metastatic cancers with microsatellite instability high (MSI-H) or deficient mismatch repair (dMMR). Unlike current standard treatments, which often rely on chemotherapy or immunotherapy alone, Nous-209 combines a vaccine strategy with pembrolizumab, an established immunotherapy. This combination aims to enhance the immune system's ability to recognize and attack cancer cells more effectively. By introducing specific cancer antigens through the vaccine, researchers hope to boost the body’s immune response, potentially leading to improved outcomes for patients with these challenging cancer types.

What evidence suggests that the Nous-209 vaccine could be an effective treatment for metastatic cancer?

Research has shown that the Nous-209 vaccine, when combined with the drug pembrolizumab, may help treat some advanced cancers. In this trial, participants in different cohorts will receive varying doses and combinations of Nous-209 and pembrolizumab. Early studies have found that this combination is safe and enhances the immune response in patients with certain gastrointestinal cancers. Initial results suggest it might shrink tumors and improve outcomes for some patients. The vaccine teaches the immune system to identify and attack cancer cells. While more research is needed, these findings offer hope for people facing these challenging cancers. ^{1 2 5 6 7}

Who Is on the Research Team?

Sven Gogov, MD

Principal Investigator

Nouscom SRL

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

Citations

1. nouscom.com nouscom.com/2022/06/06/nouscom-announces-positive-phase-1-data-of-nous-209-an-off-the-shelf-neoantigen-cancer-immunotherapy-for-the-treatment-of-dmmr-msi-h-solid-tumors-at-asco-2022/

Nouscom Announces Full Phase 1 Data of NOUS-209 NOUS-209 in combination with pembrolizumab is safe, highly immunogenic, and associated with promising early and long-term clinical efficacy in 20 MSI-H GI ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04041310

Study Details | NCT04041310 | Nous-209 Genetic Vaccine ... NOUS-209-01 is a multicenter, open-label, multiple cohorts, clinical study, designed to evaluate safety, tolerability, and immunogenicity, and to detect any ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.2515

First clinical and immunogenicity results including all ... Conclusions: The combination of the Nous-209 and pembrolizumab is safe and well tolerated, and shows signs of clinical efficacy. Nous-209 ...

4. jitc.bmj.com jitc.bmj.com/content/9/Suppl_2/A441

410 Phase I interim study results of Nous-209, an off- ... The combination of the Nous-209 genetic polyvalent cancer vaccine and pembrolizumab has been demonstrated to be safe, immunogenic, and continues to show early ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10975996/

Development of a Potency Assay for Nous-209 ... Nous-209 is now being investigated in a phase 1/2 trial in patients with metastatic gastric, colorectal, and GEJ (gastroesophageal junction) ...

6. nouscom.com nouscom.com/pipeline/

Cancer Genetic Vaccines and Armored Oncolytic Viruses NOUS-209 in combination with pembrolizumab has been demonstrated to be safe, highly immunogenic and with promising signs of clinical efficacy in dMMR/MSI-H ...

7. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04041310/

Clinical Trial: NCT04041310 - Solid Tumors NOUS-209-01 is a multicenter, open-label, multiple cohorts, First In Humans (FIH) clinical study, designed to evaluate safety, tolerability, and immunogenicity.