CLN-619 + Pembrolizumab for Cancer
Recruiting in Palo Alto (17 mi)
+22 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Cullinan Therapeutics Inc.
Must not be taking: Immunosuppressants, Corticosteroids
Disqualifiers: Active autoimmune disease, Uncontrolled hypertension, HIV, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial is testing a new drug called CLN-619 alone and with pembrolizumab in patients with advanced solid tumors. These patients may not have other treatment options. Pembrolizumab helps the immune system fight cancer, and they are seeing if CLN-619 can help too.
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, it mentions that you should not have received certain treatments like systemic anticancer treatment or immunotherapy within a specific time before starting the trial. It's best to discuss your current medications with the trial team to get a clear answer.
What data supports the effectiveness of the drug pembrolizumab in cancer treatment?
Pembrolizumab has shown effectiveness in treating various cancers, including non-small cell lung cancer and metastatic melanoma, by improving tumor response rates and prolonging response durations. It has also demonstrated superior efficacy when combined with chemotherapy in treating metastatic triple-negative breast cancer with PD-L1 positive tumors.
12345What safety information is available for the cancer treatment CLN-619 + Pembrolizumab?
Pembrolizumab (also known as Keytruda) has been associated with some side effects, including pneumonitis (lung inflammation) in 1%-5% of patients, and rare cases of type 1 diabetes. Common side effects include fatigue, cough, nausea, and rash, while more serious immune-related side effects can affect organs like the thyroid and liver.
12456What makes the drug CLN-619 + Pembrolizumab unique for cancer treatment?
The combination of CLN-619 and Pembrolizumab is unique because it combines a novel treatment (CLN-619) with Pembrolizumab, an established immune checkpoint inhibitor that enhances the immune system's ability to fight cancer by blocking the PD-1 pathway. This combination may offer a new approach to treating cancers by potentially improving the immune response against tumors.
12578Eligibility Criteria
Adults with advanced solid tumors, including specific types such as NSCLC, cervical cancer, HNSCC, and urothelial carcinoma. Participants must have measurable disease, acceptable organ function and performance status. Prior treatments are specified for each cohort. Pregnant or breastfeeding women and those unwilling to prevent pregnancy or donate sperm during the study are excluded.Inclusion Criteria
I am 18 years old or older.
My liver, kidneys, and blood counts are healthy.
I am 18 years old or older.
+20 more
Exclusion Criteria
You are currently struggling with drug or alcohol addiction.
I am currently infected with COVID-19.
I am not pregnant, breastfeeding, planning to become pregnant soon, and agree to use birth control during and after the study.
+20 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Dose Escalation
Participants with advanced solid tumors are enrolled in dose escalation cohorts treated with CLN-619 alone or in combination with pembrolizumab
24 months
Regular visits for monitoring and dose adjustments
Dose Expansion
Participants with select tumor types are enrolled in expansion cohorts treated with CLN-619 at a selected dose, alone or in combination with pembrolizumab
36 months
Every 6 weeks for the first 18 weeks, then every 9 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to 2 years
Participant Groups
The trial is testing CLN-619 alone and combined with Pembrolizumab in patients with various advanced solid tumors. It's an early-phase (Phase 1), open-label study which means both researchers and participants know what treatment is being given.
4Treatment groups
Experimental Treatment
Group I: Module B Combination Therapy Dose EscalationExperimental Treatment2 Interventions
Patients with advanced solid tumors enrolled in dose escalation cohorts treated with CLN-619 in combination with pembrolizumab
Group II: Module B Combination Therapy Cohort ExpansionExperimental Treatment2 Interventions
Patients with select tumor types enrolled in expansion cohorts treated with CLN-619 at a dose selected from the Module B Escalation arm, in combination with pembrolizumab
Group III: Module A Dose EscalationExperimental Treatment1 Intervention
Patients with advanced solid tumors enrolled in dose escalation cohorts treated with CLN-619
Group IV: Module A Cohort ExpansionExperimental Treatment1 Intervention
Patients with select solid tumor types enrolled in expansion cohorts treated with CLN-619 at a dose selected from the Module A Escalation arm
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
START MidwestSan Antonio, TX
Memorial Sloan Kettering Cancer CenterNew York, NY
City of HopeIrvine, CA
University of Alabama at BirminghamBirmingham, AL
More Trial Locations
Loading ...
Who Is Running the Clinical Trial?
Cullinan Therapeutics Inc.Lead Sponsor
Cullinan Oncology Inc.Lead Sponsor
Cullinan Oncology, LLCLead Sponsor
References
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit.
Q-TWiST analysis of pembrolizumab combined with chemotherapy as first-line treatment of metastatic triple-negative breast cancer that expresses PD-L1. [2023]In the KEYNOTE-355 (KN355) trial, pembrolizumab in combination with chemotherapy demonstrated superior efficacy and manageable safety compared with chemotherapy alone in patients with previously untreated locally recurrent inoperable and metastatic triple-negative breast cancer (mTNBC) with PD-L1 positive (Combined Positive Score [CPS]≥ 10) tumours. This study aimed to evaluate the clinical benefits and risks of pembrolizumab measured by quality-adjusted survival in the trial population.
FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]On September 4, 2014, the FDA approved pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) with a recommended dose of 2 mg/kg every 3 weeks by intravenous infusion for the treatment of patients with unresectable or metastatic melanoma who have progressed following treatment with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on demonstration of objective tumor responses with prolonged response durations in 89 patients enrolled in a randomized, multicenter, open-label, dose-finding, and activity-estimating phase 1 trial. The overall response rate (ORR) by blinded independent central review per RECIST v1.1 was 24% (95% confidence interval, 15-34); with 6 months of follow-up, 86% of responses were ongoing. The most common (≥20%) adverse reactions were fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. Immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, hypophysitis, and thyroid disorders. The benefits of the observed ORR with prolonged duration of responses outweighed the risks of immune-mediated adverse reactions in this life-threatening disease and represented an improvement over available therapy. Important regulatory issues in this application were role of durability of response in the evaluation of ORR for accelerated approval, reliance on data from a first-in-human trial, and strategies for dose selection. Clin Cancer Res; 23(19); 5666-70. ©2017 AACR.
Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]Pembrolizumab (Keytruda) is a monoclonal antibody against the programmed cell death-1 (PD-1) receptor on lymphocytes, which is one of the immune checkpoint inhibitors (ICIs) approved for multiple solid and hematologic malignancies. Although ICIs have proven to be more effective and less toxic compared to chemotherapy, there are reports of adverse side effects with ICIs. For example, pneumonitis is a potentially lethal side effect occurring in 1%-5% of patients who received ICIs in clinical trials, and there are case reports with clinical and radiological features of checkpoint inhibitor-pneumonitis (CIP).
Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]Pembrolizumab (Keytruda; Merck Sharp & Dohme) is a humanized IgG4 monoclonal antibody used in cancer immunotherapy. It targets the programmed cell death-1 (PD-1) receptor, which is important in maintaining self-tolerance. However, immune checkpoint blockade is associated with a risk for immune-related adverse events (irAEs) potentially affecting the endocrine organs. Type 1 diabetes mellitus is a rare irAE of PD-1 inhibitors, occurring in 0.2% of cases.
Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. [2021]The programmed cell death 1 (PD-1) pathway represents a major immune checkpoint, which may be engaged by cells in the tumor microenvironment to overcome active T-cell immune surveillance. Pembrolizumab (Keytruda®, MK-3475) is a potent and highly selective humanized mAb of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. This blockade enhances the functional activity of T cells to facilitate tumor regression and ultimately immune rejection. Pembrolizumab binds to human and cynomolgus monkey PD-1 with picomolar affinity and blocks the binding of human and cynomolgus monkey PD-1 to PD-L1 and PD-L2 with comparable potency. Pembrolizumab binds both the C'D and FG loops of PD-1. Pembrolizumab overcomes human and cynomolgus monkey PD-L1-mediated immune suppression in T-cell cultures by enhancing IL2 production following staphylococcal enterotoxin B stimulation of healthy donor and cancer patient cells, and IFNγ production in human primary tumor histoculture. Ex vivo and in vitro studies with human and primate T cells show that pembrolizumab enhances antigen-specific T-cell IFNγ and IL2 production. Pembrolizumab does not mediate FcR or complement-driven effector function against PD-1-expressing cells. Pembrolizumab displays dose-dependent clearance and half-life in cynomolgus monkey pharmacokinetic and toxicokinetic studies typical for human IgG4 antibodies. In nonhuman primate toxicology studies, no findings of toxicologic significance were observed. The preclinical data for pembrolizumab are consistent with the clinical anticancer activity and safety that has been demonstrated in human clinical trials.
Perforation of small intestinal metastasis of lung adenocarcinoma treated with pembrolizumab: a case report. [2020]Pembrolizumab is an immune checkpoint inhibitor and is an anti-human programmed cell death-1 (PD-1) monoclonal antibody. Pembrolizumab is used for non-small cell lung carcinoma with high programmed cell death ligand-1 (PD-L1) expression. It has been found that better overall survival can be obtained using pembrolizumab compared to the existing chemotherapy. We report a case of perforation of small intestinal metastasis after pembrolizumab treatment.