SNS-101 + Cemiplimab for Cancer

Not currently recruiting at 9 trial locations

Overseen By Janine McDermott

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Sensei Biotherapeutics, Inc.

Must not be taking: Anti-PD-1, PD-L1, Chemotherapy, Biologics

Disqualifiers: Brain metastasis, Severe allergies, Pregnancy, others

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

Compensation: Varies

Number of Visits: 63

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called SNS-101, used alone or with cemiplimab (an immunotherapy drug), to determine its safety and effectiveness for individuals with advanced solid tumors that cannot be surgically removed. It targets those who have tried standard treatments without success or are ineligible for them, especially if they have cancers such as colorectal, head and neck, melanoma, or lung cancer. Participants must have a measurable disease and be willing to provide tumor biopsy samples. 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 the chance to contribute to groundbreaking cancer treatment advancements.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as anti-PD-1/PD-L1 therapies, chemotherapy, or other investigational drugs, at least 2 weeks before starting the study. It's best to discuss your specific medications with the trial team to see if they need to be paused.

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

Studies have shown that SNS-101 is generally safe. Patients in earlier trials tolerated it well both alone and with cemiplimab. No severe side effects prevented patients from taking higher doses, indicating that the treatment can be tested safely at various doses.

Cemiplimab has approval for other uses, so its side effects are well-known and usually manageable. Early research suggests that SNS-101 and cemiplimab form a safe combination. However, ongoing trials are necessary to confirm their safety for individuals with advanced solid tumors. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about SNS-101 and its combination with Cemiplimab because these treatments offer a fresh approach to targeting cancer. Unlike standard cancer treatments that often focus on directly killing cancer cells, SNS-101 is designed to enhance the immune system's natural ability to fight cancer by blocking a specific protein that tumors use to evade immune detection. When combined with Cemiplimab, a PD-1 inhibitor that also boosts the immune response, there is potential for a powerful synergistic effect, possibly leading to more effective outcomes than current options. This combination could provide a new lifeline for patients, especially those who haven't responded well to existing therapies.

What evidence suggests that this trial's treatments could be effective for advanced solid tumors?

Research has shown that SNS-101, a treatment in this trial, may help treat advanced solid tumors when used alone or with cemiplimab, another treatment option in this trial. In one study, a patient with colorectal cancer experienced a 27% reduction in tumor size after 18 weeks of treatment with SNS-101 and cemiplimab. Another study indicated that SNS-101 can be safely administered in high doses, which is encouraging for its potential effectiveness. SNS-101 targets VISTA, a protein that cancer cells use to evade the immune system. When combined with cemiplimab, a PD-1 blocker, it may help the immune system better detect and attack cancer. Early research also suggests it might help with tumors that don't respond to other treatments. ^{2 4 6 7 8}

Who Is on the Research Team?

Ron Weitzman, MD

Principal Investigator

Sensei Biotherapeutics, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors who've tried standard treatments without success or can't receive them. They must have measurable disease, good organ function, and a life expectancy of at least 3 months. Women and men able to have children must use effective birth control. People can't join if they've had certain recent cancer treatments, severe reactions to similar drugs, brain metastases, or are pregnant/breastfeeding.

Inclusion Criteria

My cancer is advanced, cannot be surgically removed, or has spread.

My cancer can be measured by tests.

I agree to give samples of my tumor before and during treatment.

Exclusion Criteria

I haven't had treatment for another cancer within the last 2 years, except for early-stage cancer treated with the aim of cure.

I experienced severe side effects from previous immunotherapy.

I am not pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Monotherapy Dose Escalation and Dose Expansion

SNS-101 is administered alone every 21 days to determine safety, tolerability, and optimal dosing

Approximately 15 months

Every 21 days

Phase 1 Combination Dose Escalation and Dose Expansion

SNS-101 is administered in combination with cemiplimab every 21 days to determine safety, tolerability, and optimal dosing

Approximately 15 months

Every 21 days

Phase 2 Cohort Expansion

SNS-101 is administered alone or in combination with cemiplimab to evaluate efficacy in specific tumor types

Approximately 1 year

Every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days after the last dose

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab
• SNS-101

Trial Overview The study tests SNS-101 (an anti-VISTA antibody) alone or with Cemiplimab in patients with various advanced cancers. It aims to assess the safety and effectiveness of these therapies while monitoring how the body processes them.

How Is the Trial Designed?

Group I: Part C - Cohort Expansion - SNS-101 alone or in combination with cemiplimab Experimental Treatment 2 Interventions

SNS-101 IV alone or in combination with cemplimab IV every 21 days at the RP2D.

Group II: Part B - SNS-101 in combination with cemiplimab and Dose Expansion Experimental Treatment 2 Interventions

SNS-101 IV and cemiplimab IV every 21 days. Patients will initially enroll in dose escalation cohorts.

Group III: Part A - SNS-101 Monotherapy Dose Escalation and Dose Expansion Experimental Treatment 1 Intervention

SNS-101 IV alone every 21 days. Patients will initially enroll in dose escalation cohorts.

Cemiplimab is already approved in European Union, United States, Canada, Brazil for the following indications:

Approved in European Union as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in United States as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Basal cell carcinoma (BCC)
• Non-small cell lung cancer (NSCLC)

Approved in Canada as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in Brazil as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)

Who Is Running the Clinical Trial?

Sensei Biotherapeutics, Inc.

Lead Sponsor

Trials

4

Recruited

210+

Regeneron Pharmaceuticals

Industry Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Published Research Related to This Trial

Cemiplimab-rwlc (Libtayo) is an FDA-approved immunotherapy for advanced cutaneous squamous cell carcinoma (CSCC) that works by blocking the PD-1 receptor, enhancing the immune system's ability to fight tumors.

Clinical trials have shown that cemiplimab is effective in treating CSCC, although common side effects and safety issues were noted, highlighting the need for ongoing research to improve treatment outcomes and reduce toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma. Ahmed, SR., Petersen, E., Patel, R., et al.[2019]

Cemiplimab (Libtayo®) is the first approved immunotherapy for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC) who cannot undergo surgery or radiotherapy, showing a clinically significant objective response rate in the phase II EMPOWER-CSCC 1 trial.

The treatment has a durable effect, with the median duration of response and overall survival not yet reached, and it has an acceptable safety profile, with manageable immune-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab: A Review in Advanced Cutaneous Squamous Cell Carcinoma. Lee, A., Duggan, S., Deeks, ED.[2020]

In a phase II trial involving 84 patients with advanced pancreatic cancer, the addition of cetuximab to gemcitabine and cisplatin did not significantly improve objective response rates or overall survival compared to gemcitabine and cisplatin alone.

Despite no increase in toxic effects from cetuximab, the study concluded that this combination treatment should not be pursued in further phase III trials, as it did not demonstrate any added benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab plus gemcitabine and cisplatin compared with gemcitabine and cisplatin alone in patients with advanced pancreatic cancer: a randomised, multicentre, phase II trial. Cascinu, S., Berardi, R., Labianca, R., et al.[2022]

Cemiplimab-rwlc is a newly approved PD-1/L1 inhibitor for first-line treatment of metastatic non-small cell lung cancer (NSCLC) without EGFR or ALK mutations, either alone or with chemotherapy.

This review highlights the differences in patient populations studied for cemiplimab compared to other treatments, emphasizing its role in expanding options for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on Cemiplimab-rwlc in the Treatment of Non-Small Cell Lung Cancer (NSCLC): Focus on Patient Selection and Considerations. Ahn, J., Nagasaka, M.[2023]

Cisplatin combined with S-1 has shown effectiveness in treating recurrent non-small cell lung cancer (NSCLC), with two case reports demonstrating partial tumor response in patients who had undergone multiple prior chemotherapy regimens.

While the treatment was associated with manageable side effects, including hematologic toxicities like neutropenia and anemia, there were no treatment-related deaths, suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Two cases with recurrent non-small cell lung cancer successfully treated with cisplatin and S-1]. Hirose, T., Hosaka, T., Nakashima, M., et al.[2016]

Cemiplimab, a PD-1 inhibitor, shows significant improvements in overall survival (OS) and progression-free survival (PFS) compared to EGFR inhibitors and pembrolizumab, with hazard ratios indicating a strong benefit.

In comparison to platinum-based chemotherapy, cemiplimab also demonstrated superior efficacy in improving overall survival for patients with advanced cutaneous squamous cell carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy of cemiplimab versus other systemic treatments for advanced cutaneous squamous cell carcinoma. Keeping, S., Xu, Y., Chen, CI., et al.[2021]

At 35 months of follow-up, patients with advanced non-small-cell lung cancer and high PD-L1 expression treated with cemiplimab had a median overall survival of 26.1 months, significantly better than the 13.3 months for those receiving chemotherapy, indicating a strong survival benefit from cemiplimab.

The addition of chemotherapy to cemiplimab after disease progression resulted in a median overall survival of 15.1 months, suggesting that this combination could be an effective second-line treatment option for patients with advanced non-small-cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line cemiplimab monotherapy and continued cemiplimab beyond progression plus chemotherapy for advanced non-small-cell lung cancer with PD-L1 50% or more (EMPOWER-Lung 1): 35-month follow-up from a mutlicentre, open-label, randomised, phase 3 trial. Özgüroğlu, M., Kilickap, S., Sezer, A., et al.[2023]

Cemiplimab is the first FDA-approved treatment for patients with advanced cutaneous squamous cell carcinoma (CSCC) who cannot undergo curative surgery or radiation, demonstrating rapid and substantial antitumor efficacy in phase II clinical trials.

The treatment has an acceptable safety profile, with low rates of treatment discontinuation (7%) and death (3%), although current recommendations are based mainly on phase II data due to the lack of an approved comparator agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab in advanced cutaneous squamous cell carcinoma. Naik, PP.[2022]

In a phase 3 study involving 357 patients with advanced squamous non-small cell lung cancer (sqNSCLC), sintilimab combined with platinum and gemcitabine (GP) significantly improved progression-free survival (PFS) compared to GP alone, with a hazard ratio of 0.536, indicating a strong clinical benefit.

The safety profile of sintilimab-GP was acceptable, with similar rates of severe treatment-related adverse events (86.6% for sintilimab-GP vs. 83.1% for placebo-GP) and no new safety concerns identified, suggesting it is a viable first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sintilimab Plus Platinum and Gemcitabine as First-Line Treatment for Advanced or Metastatic Squamous NSCLC: Results From a Randomized, Double-Blind, Phase 3 Trial (ORIENT-12). Zhou, C., Wu, L., Fan, Y., et al.[2022]

Cemiplimab is a PD-1 monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, which is crucial for enhancing the immune response against cancer cells.

In September 2018, cemiplimab received FDA approval for treating patients with metastatic or locally advanced cutaneous squamous cell carcinoma who cannot undergo curative surgery or radiation, marking a significant advancement in cancer treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab: First Global Approval. Markham, A., Duggan, S.[2023]

This phase I/II clinical trial is investigating the safety and efficacy of a combination treatment involving selumetinib, tremelimumab, and durvalumab in 40 patients with previously treated, unresectable non-small-cell lung cancer (NSCLC).

The study aims to determine the maximum tolerated dose and progression-free survival, while also exploring biomarkers of response and resistance, which could help tailor future treatments for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II Trial of Immunotherapy With Durvalumab and Tremelimumab With Continuous or Intermittent MEK Inhibitor Selumetinib in NSCLC: Early Trial Report. Gaudreau, PO., Lee, JJ., Heymach, JV., et al.[2021]

In A549 cell lines, the combination of TRAIL with chemotherapeutic agents like cisplatin, Taxol, or actinomycin D significantly increased cytotoxicity compared to TRAIL alone, indicating a synergistic effect.

In a nude mice model, TRAIL combined with cisplatin resulted in a tumor inhibition rate of 76.8%, compared to 28.3% for TRAIL alone, suggesting that this combination therapy could enhance treatment efficacy without relying on changes in TRAIL receptor expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergistic antitumor activity of TRAIL combined with chemotherapeutic agents in A549 cell lines in vitro and in vivo. Fan, QL., Zou, WY., Song, LH., et al.[2006]

Citations

1. investors.senseibio.com investors.senseibio.com/news-releases/news-release-details/sensei-biotherapeutics-presents-promising-clinical-data-phase-1

Sensei Biotherapeutics Presents Promising Clinical Data ... One MSS colorectal cancer (CRC) patient that received SNS-101 plus cemiplimab remained on study for 18 weeks and had tumor regression of 27%.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2600

Initial results from a first-in-human phase 1 study of SNS ... Conclusions: pH selective SNS-101, both alone and in combo with cemi, has been safely administered at doses that are ~50x higher than doses ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10995192/

VISTA checkpoint inhibition by pH-selective antibody SNS ... SNS-101 shows in vivo efficacy when combined with a PD-1 inhibitor, modulates cytokine and chemokine signaling, and alters the tumor microenvironment.

4. cancernetwork.com cancernetwork.com/view/solnerstotug-shows-promising-preliminary-data-in-pd-l1-resistant-tumors

Solnerstotug Shows Promising Preliminary Data in PD-L1 ... Solnerstotug (SNS-101) with or without cemiplimab (Libtayo) showed promising preliminary dose expansion data as a treatment for PD-L1–resistant tumors.

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)03812-7/fulltext

1078TiP Phase I/II, open-label study evaluating the safety, ... Based on preclinical data, SNS-101, either as monotherapy or in combination therapy with a PD-1 blocker, cemiplimab, is expected to exhibit an acceptable ...

6. investors.senseibio.com investors.senseibio.com/news-releases/news-release-details/sensei-biotherapeutics-reports-favorable-clinical-data-sns-101

Sensei Biotherapeutics Reports Favorable Clinical Data for ... Clinical dose escalation data for SNS-101 monotherapy show well tolerated safety profile, potentially best-in-class pharmacokinetics, and encouraging cytokine ...

7. nature.com nature.com/articles/s41467-024-47256-x

VISTA checkpoint inhibition by pH-selective antibody SNS ... We introduce SNS-101, a pH-selective antibody designed to mitigate rapid clearance and cytokine release syndrome, enhancing the therapeutic efficacy of PD-1 ...

8. synapse.patsnap.com synapse.patsnap.com/article/sensei-biotherapeutics-shows-promising-phase-1-data-for-sns-101

Sensei Biotherapeutics Shows Promising Phase 1 Data for ... Safety data revealed that SNS-101 was well-tolerated as both a monotherapy and in combination with cemiplimab, without any dose-limiting ...