S095029 + Sym021 for Colorectal Cancer

Not currently recruiting at 4 trial locations

Overseen By Institut de Recherches Internationales Servier, Clinical Studies Department

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Institut de Recherches Internationales Servier

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: HIV, Active infection, Autoimmune, others

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

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, S095029 (also known as Libtayo or cemiplimab-rwlc) and Sym021, to assess their safety and tolerability in individuals with advanced, inoperable cancers. The trial aims to determine if these treatments can slow or halt cancer growth. Suitable participants have a solid tumor cancer that has progressed after other treatments and cannot be surgically treated. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic immunosuppressive therapy, you may need to stop, as it is listed in the exclusion criteria.

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

Research has shown that the treatment S095029 is generally safe when used alone. In previous studies, only a small number of participants discontinued the treatment (7%), and a few deaths occurred (3%). This indicates that most participants tolerated the drug well.

When combined with Sym021, S095029 remains safe, with no significant increase in serious issues. However, like many treatments, it can cause side effects such as tiredness, skin rash, or diarrhea.

Overall, early results suggest that S095029, whether used alone or with Sym021, is well-tolerated by most people. This makes it a potentially safe option for those considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about S095029 and Sym021 because these treatments represent a new approach in combating colorectal cancer. Unlike standard treatments like chemotherapy, which target all rapidly dividing cells, S095029 and Sym021 are designed to specifically target cancer cells by engaging the immune system. S095029 is a novel agent that may enhance the immune response against cancer cells, while Sym021 is a monoclonal antibody that blocks a protein called PD-1, which cancer cells use to hide from the immune system. This targeted approach has the potential to be more effective and less harmful to healthy cells, offering hope for improved outcomes in patients.

What evidence suggests that S095029 and Sym021 could be effective for colorectal cancer?

Research has shown that using S095029 with Sym021 may be promising for treating colorectal cancer. In this trial, participants will be assigned to different treatment arms: one will receive S095029 alone, while another will receive the combination of S095029 and Sym021. In earlier studies, participants who received this combination lived for a median of 21.9 months, a favorable outcome compared to other treatments. Most side effects were manageable, suggesting it could be a safe option. S095029 uses an antibody to help the immune system attack cancer cells, while Sym021 is designed to enhance this effect, further boosting the body's natural defense against cancer. These early findings suggest that this combination could effectively treat advanced solid tumors like colorectal cancer. ^{4 5 6 7 8}

Who Is on the Research Team?

Nehal Lakhani MD, MD, PhD

Principal Investigator

Director of Clinical Research START Midwest

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors, including metastatic HER2+ gastric and colorectal cancers. Participants must have tried standard treatments without success or be intolerant to them. They need good heart, liver, kidney, and blood function and can't have had major surgery recently or suffer from active infections or certain chronic conditions.

Inclusion Criteria

Patients with skin rash of Grade > 1 from prior anti-EGFR

You have a major problem with your digestive system.

Patients with available archived tumor biopsy specimens or agree to mandatory biopsy

Exclusion Criteria

You have a past history of liver disease called cirrhosis.

You are currently pregnant or breastfeeding.

Patients with serious/active/uncontrolled infection or infection requiring parenteral antibiotics, within 2 weeks prior to first IMP administration

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation 1a

Participants receive S095029 as monotherapy to assess safety and tolerability

4 weeks

1 visit per week (in-person)

Dose Escalation 1b

Participants receive S095029 in combination with Sym021 to assess safety and tolerability

4 weeks

1 visit per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• anti-HER2 therapy
• futuximab/modotuximab
• S095029
• Sym021

Trial Overview The study tests S095029 alone and combined with Sym021 in patients with various solid tumors. It will expand to test triple combinations involving anti-HER2 therapy (futuximab/modotuximab) specifically in those with metastatic gastric or colorectal cancers.

How Is the Trial Designed?

Group I: Dose escalation 1b: S95029 and Sym021 Experimental Treatment 1 Intervention

Group II: Dose escalation 1a: S95029 Experimental Treatment 1 Intervention

S095029 is already approved in United States, European Union for the following indications:

Approved in United States as Libtayo for:

• Advanced non-small cell lung cancer (NSCLC) with high PD-L1 expression and no EGFR, ALK, or ROS1 aberrations
• Advanced NSCLC in combination with platinum-based chemotherapy

Approved in European Union as Libtayo for:

• Not specified in the provided sources, but generally approved for similar indications as in the US

Who Is Running the Clinical Trial?

Institut de Recherches Internationales Servier

Lead Sponsor

Trials

91

Recruited

67,100+

ADIR, a Servier Group company

Industry Sponsor

Trials

33

Recruited

4,300+

Published Research Related to This Trial

In a phase II trial involving 35 patients with untreated metastatic colorectal cancer, the combination of gefitinib, capecitabine, and oxaliplatin resulted in an 80% disease control rate, with 8.6% achieving a complete response and 40% a partial response.

The treatment led to a median overall survival of 21.9 months, which is promising compared to previous regimens, and the side effects were manageable, primarily consisting of diarrhea and vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of gefitinib in combination with capecitabine and oxaliplatin as first-line chemotherapy in patients with advanced colorectal cancer. Gelibter, AJ., Gamucci, T., Pollera, CF., et al.[2018]

Cemiplimab, administered as monotherapy or in combination with hypofractionated radiation therapy, showed a 10% objective response rate in patients with recurrent or metastatic cervical cancer, particularly in those with squamous histology, indicating its potential efficacy in this subgroup.

The most common side effects were diarrhea, fatigue, and hypokalemia, affecting 35%, 25%, and 25% of patients respectively, suggesting that while cemiplimab has anti-tumor activity, it also has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1 blockade in recurrent or metastatic cervical cancer: Data from cemiplimab phase I expansion cohorts and characterization of PD-L1 expression in cervical cancer. Rischin, D., Gil-Martin, M., González-Martin, A., et al.[2021]

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]

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]

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]

Cemiplimab, an anti-PD-1 monoclonal antibody, demonstrated a favorable safety profile in a study of 60 patients with advanced solid tumors, with no dose-limiting toxicities and manageable treatment-emergent adverse events like fatigue and nausea.

The treatment showed promising antitumor activity, with 2 complete responses and 7 partial responses, and responses lasting at least 12 months in some patients, indicating its potential effectiveness when combined with hypofractionated radiotherapy and/or cyclophosphamide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-In-Human Study of Cemiplimab Alone or In Combination with Radiotherapy and/or Low-dose Cyclophosphamide in Patients with Advanced Malignancies. Papadopoulos, KP., Johnson, ML., Lockhart, AC., et al.[2021]

Citations

1. oncodaily.com oncodaily.com/drugs/cemiplimab-rwlc-libtayo

Cemiplimab-rwlc (Libtayo) Updates 2025: Uses in cancer, ... Libtayo significantly improved median overall survival, extending it to 26.1 months compared to 13.3 months with chemotherapy (hazard ratio [HR] ...

2. newsroom.regeneron.com newsroom.regeneron.com/news-releases/news-release-details/libtayor-cemiplimab-plus-chemotherapy-results-five-years

Libtayo® (cemiplimab) Plus Chemotherapy Results at Five ... At this year's WCLC, five-year efficacy results, with a median follow-up of 60.9 months, found Libtayo plus chemotherapy remained superior to ...

3. withpower.com withpower.com/trial/phase-1-colorectal-neoplasms-9-2021-cce40

S095029 + Sym021 for Colorectal Cancer The treatment led to a median overall survival of 21.9 months, which is promising compared to previous regimens, and the side effects were manageable, primarily ...

4. targetedonc.com targetedonc.com/view/unpacking-the-data-behind-adjuvant-cemiplimab-s-fda-approval

Unpacking the Data Behind Adjuvant Cemiplimab's FDA ... The 24-month DFS rates for cemiplimab and placebo treatment were 87.1% and 64.1%, respectively. This effect was observed across all tumor ...

5. libtayo.com libtayo.com/cscc/why-libtayo

Taking LIBTAYO® (cemiplimab-rwlc) | Advanced CSCC LIBTAYO study results · 15 out of 56 patients (27%) saw tumors shrink (partial response) · 11 out of 56 patients (20%) saw tumors disappear completely (complete ...

6. investor.regeneron.com investor.regeneron.com/news-releases/news-release-details/libtayor-cemiplimab-rwlc-approved-us-first-and-only

Libtayo® (cemiplimab-rwlc) Approved in the U.S. as First ... Approval based on pivotal Phase 3 C-POST trial showing Libtayo significantly reduced the risk of disease recurrence or death by 68% compared ...

7. libtayo.com libtayo.com/high-risk-cscc/study-results

LIBTAYO® (cemiplimab-rwlc) Study Results | High-Risk CSCC Discover study results and possible side effects of the adjuvant treatment of LIBTAYO® (cemiplimab-rwlc) in adults with high-risk CSCC.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05162755

Study Details | NCT05162755 | S095029 as Monotherapy ... The purpose of the study is to investigate the safety, tolerability, and preliminary anti-neoplastic activity of S095029 alone and in combination with Sym021