CLN-619 + Pembrolizumab for Cancer

Recruiting at 22 trial locations

Overseen By Timna O Serino

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Cullinan Therapeutics Inc.

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Active autoimmune disease, Uncontrolled hypertension, HIV, others

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

Compensation: Varies

Number of Visits: 6

410 Participants Needed

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. ^{1 2 3 4 5}

What 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. ^{1 2 4 5 6}

What 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. ^{1 2 5 7 8}

Eligibility 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.

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.

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

Treatment Details

Interventions

• CLN-619
• Pembrolizumab

Trial Overview 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.

Participant Groups

Group I: Module B Combination Therapy Dose Escalation Experimental Treatment 2 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 Expansion Experimental Treatment 2 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 Escalation Experimental Treatment 1 Intervention

Patients with advanced solid tumors enrolled in dose escalation cohorts treated with CLN-619

Group IV: Module A Cohort Expansion Experimental Treatment 1 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

Who Is Running the Clinical Trial?

Cullinan Therapeutics Inc.

Lead Sponsor

Trials

9

Recruited

1,000+

Cullinan Oncology Inc.

Lead Sponsor

Trials

6

Recruited

710+

Cullinan Oncology, LLC

Lead Sponsor

Trials

7

Recruited

990+

Findings from Research

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

In the KEYNOTE-355 trial, patients with previously untreated metastatic triple-negative breast cancer (mTNBC) who received pembrolizumab combined with chemotherapy experienced a significant improvement in quality-adjusted survival, gaining an average of 3.7 months more time without symptoms or treatment toxicity compared to those receiving chemotherapy alone.

The benefits of pembrolizumab plus chemotherapy increased over time, with a 20% relative gain in quality-adjusted survival at a maximum follow-up of 52 months, indicating both efficacy and manageable safety in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Q-TWiST analysis of pembrolizumab combined with chemotherapy as first-line treatment of metastatic triple-negative breast cancer that expresses PD-L1. Huang, M., O'Shaughnessy, J., Haiderali, A., et al.[2023]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab (Keytruda) effectively blocks the PD-1 pathway, enhancing T-cell activity against tumors, which supports its role in promoting tumor regression and immune rejection.

Preclinical studies in cynomolgus monkeys showed that pembrolizumab has a favorable safety profile with no significant toxicological findings, aligning with its demonstrated safety and efficacy in human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. Hutchins, B., Starling, GC., McCoy, MA., et al.[2021]

Pembrolizumab, an immune checkpoint inhibitor used for treating non-small cell lung carcinoma, has been associated with improved overall survival compared to traditional chemotherapy, but it can also lead to serious side effects.

This case report highlights a rare but critical complication: a 62-year-old man experienced small intestinal perforation due to metastatic lung adenocarcinoma after receiving pembrolizumab, emphasizing the need for careful monitoring of patients for potential autoimmune side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perforation of small intestinal metastasis of lung adenocarcinoma treated with pembrolizumab: a case report. Sato, S., Senmaru, N., Ishido, K., et al.[2020]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

3. England pubmed.ncbi.nlm.nih.gov

Q-TWiST analysis of pembrolizumab combined with chemotherapy as first-line treatment of metastatic triple-negative breast cancer that expresses PD-L1. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. [2021]

8. Germany pubmed.ncbi.nlm.nih.gov

Perforation of small intestinal metastasis of lung adenocarcinoma treated with pembrolizumab: a case report. [2020]