86 Participants Needed

CLN-617 + Pembrolizumab for Solid Tumors

Recruiting at 5 trial locations
MS
AG
SM
Overseen ByShane McLoughlin
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

CLN-617-001 is a Phase 1, open-label, dose escalation, dose optimization and dose expansion study of CLN-617 alone and in combination with Pembrolizumab in patients with advanced solid tumors

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, certain medications like systemic anticancer treatments, immunotherapy, and immunosuppressive medications must not be taken within a specific period before starting the trial. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the treatment CLN-617 + Pembrolizumab for solid tumors?

Research shows that combining cytokines like IL-2 and IL-12 with antibodies can enhance their ability to target and destroy cancer cells, as seen in studies where similar fusion proteins effectively reduced tumor growth and improved survival in animal models.12345

What safety information is available for the treatment CLN-617 + Pembrolizumab?

Pembrolizumab, also known as Keytruda, has been studied for safety in various conditions. It can cause side effects like fatigue, cough, nausea, and more serious immune-related issues such as pneumonitis (lung inflammation), colitis (colon inflammation), and thyroid problems. In nonhuman primate studies, pembrolizumab showed no significant toxic effects.678910

What makes the drug CLN-617 + Pembrolizumab unique for treating solid tumors?

The combination of CLN-617, an IL2/IL12 fusion protein, with Pembrolizumab (Keytruda) is unique because it combines a novel fusion protein that may enhance immune response with an established immune checkpoint inhibitor that blocks PD-1, potentially offering a more effective approach to activating the immune system against solid tumors.6791011

Eligibility Criteria

Adults (18+) with advanced solid tumors who have measurable lesions, appropriate for pembrolizumab treatment, and a life expectancy of at least 12 weeks. They must have normal organ function, resolved prior therapy toxicities to Grade 1 or stable Grade 2, except alopecia. Excludes those with uncontrolled diseases like heart issues or diabetes, active infections including HIV/Hepatitis B/C and COVID-19, recent immunosuppressive treatments or cancer therapies.

Inclusion Criteria

I am 18 years old or older.
I am eligible for the dose expansion part of the trial.
I have an advanced cancer that cannot be cured and can be injected for treatment.
See 18 more

Exclusion Criteria

A serious uncontrolled medical disorder that would impair the ability of the patient to receive protocol therapy or whose control may be jeopardized by the complications of this therapy. These criteria include, but are not limited to the following:
CD4+ T cell counts ≤ 350 cells/uL
Blood hepatitis B DNA or HCV RNA are detectable
See 34 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Patients with advanced solid tumors are treated with CLN-617 alone and in combination with pembrolizumab to determine the safety and optimal dose

24 months

Dose Optimization

Patients receive selected doses of CLN-617 in combination with pembrolizumab to optimize dosing

24 months

Dose Expansion

Patients with advanced melanoma or head and neck squamous cell carcinoma are treated with CLN-617 in combination with pembrolizumab to expand the study population

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • CLN-617
  • Pembrolizumab
Trial OverviewThe trial is testing CLN-617 alone and combined with Pembrolizumab in patients with advanced solid tumors. It's an early-phase study that includes dose escalation to find the safest dose that works best before expanding to more patients.
Participant Groups
3Treatment groups
Experimental Treatment
Group I: CLN-617 Dose Optimization (Part B)Experimental Treatment2 Interventions
Patients with Advanced Solid Tumors enrolled in dose optimization receiving selected doses of CLN-617 in combination with pembrolizumab
Group II: CLN-617 Dose Expansion (Part C)Experimental Treatment2 Interventions
Patients with Advanced Melanoma or Head and Neck Squamous Cell Carcinoma (HNSCC) enrolled in dose expansion treated with CLN-617 in combination with pembrolizumab
Group III: CLN-617 Dose Escalation (Part A)Experimental Treatment2 Interventions
Patients with Advanced Solid Tumors enrolled in dose escalation cohorts treated with CLN-617 alone and in combination with pembrolizumab

Find a Clinic Near You

Who Is Running the Clinical Trial?

Cullinan Therapeutics Inc.

Lead Sponsor

Trials
9
Recruited
1,000+

Cullinan Oncology, LLC

Lead Sponsor

Trials
7
Recruited
990+

Cullinan Oncology Inc.

Lead Sponsor

Trials
6
Recruited
710+

Findings from Research

Antibody-cytokine fusion proteins, or immunocytokines, show promise in enhancing cancer treatment by delivering cytokines directly to tumors, potentially increasing their anticancer effects while minimizing side effects.
While some immunocytokines are in late-stage clinical trials, further research is needed to understand their mechanisms and optimize their use in combination with other therapies to improve efficacy and safety.
Antibody-Cytokine Fusions: Versatile Products for the Modulation of Anticancer Immunity.Neri, D.[2020]
A study on antibody-cytokine fusion proteins showed that using a tandem-diabody format for the IL12 fusion protein significantly improved tumor uptake and tumor-to-organ ratios in tumor-bearing mice compared to the IgG1 format.
The optimization of the linker connecting the IL12 to the antibody revealed that a specific 15-amino acid linker provided the best tumor targeting, allowing for longer retention at the tumor site and quicker clearance from the bloodstream and normal organs.
A novel anti-cancer L19-interleukin-12 fusion protein with an optimized peptide linker efficiently localizes in vivo at the site of tumors.Ongaro, T., Matasci, M., Cazzamalli, S., et al.[2019]
Antibody-cytokine fusion proteins, specifically ch225-IL2 and ch14.18-IL2, showed complete inhibition of hepatic and pulmonary metastases in melanoma when tested in mice, outperforming traditional treatments that combined antibodies with recombinant IL-2.
The fusion proteins not only effectively targeted tumors but also significantly increased survival times of treated mice, more than doubling their lifespan compared to those receiving standard antibody and IL-2 treatments.
Eradication of human hepatic and pulmonary melanoma metastases in SCID mice by antibody-interleukin 2 fusion proteins.Becker, JC., Pancook, JD., Gillies, SD., et al.[2019]

References

Antibody-Cytokine Fusions: Versatile Products for the Modulation of Anticancer Immunity. [2020]
A novel anti-cancer L19-interleukin-12 fusion protein with an optimized peptide linker efficiently localizes in vivo at the site of tumors. [2019]
Eradication of human hepatic and pulmonary melanoma metastases in SCID mice by antibody-interleukin 2 fusion proteins. [2019]
An Antibody-Tumor Necrosis Factor Fusion Protein that Synergizes with Oxaliplatin for Treatment of Colorectal Cancer. [2021]
A single-chain IL-12 IgG3 antibody fusion protein retains antibody specificity and IL-12 bioactivity and demonstrates antitumor activity. [2021]
Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]
Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. [2021]
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]
FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]
11.United Statespubmed.ncbi.nlm.nih.gov
Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. [2022]