CLN-619 + Pembrolizumab for Cancer

(MICA Trial)

Not currently recruiting at 24 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This clinical trial explores a new treatment option, CLN-619, for individuals with advanced solid tumors. The trial tests the safety and effectiveness of CLN-619 both alone and in combination with pembrolizumab, a medication already used for some cancers. Participants may qualify if they have advanced solid tumors that cannot be surgically removed, such as certain types of lung, cervical, or endometrial cancer. The study aims to find improved treatments for these challenging cancer types. 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, 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.

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

Research has shown that CLN-619, whether used alone or with pembrolizumab, is generally safe. One study found that using CLN-619 by itself was well-tolerated and had positive effects on various tumor types, indicating the treatment's general safety for patients. When combined with pembrolizumab, the safety results remained positive.

Some patients experienced temporary increases in cytokine levels, proteins that help cells communicate. These levels returned to normal a few hours after the first dose. Such changes are common and usually not harmful.

Overall, evidence from these studies suggests that CLN-619, on its own or with pembrolizumab, is generally safe and well-tolerated in people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments in this trial because they present new ways to tackle cancer. CLN-619 is unique because it targets the immune system differently than most standard cancer treatments, which often rely on chemotherapy or traditional immunotherapies. By combining CLN-619 with pembrolizumab, a well-known immunotherapy, there’s potential to enhance the body’s ability to fight tumors more effectively. Additionally, CLN-619 is being tested in various combinations, such as with chemotherapy or Dato-DXd, aiming to broaden its effectiveness across different cancer types. This multi-faceted approach could offer more personalized and potentially more effective treatment options for patients with specific tumor types.

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

Research has shown that CLN-619, when used alone, has positive effects in treating various solid tumors. Patients have experienced safety and noticeable tumor shrinkage. CLN-619 blocks certain proteins on tumor cells, making them easier for the immune system to detect. In this trial, some participants will receive CLN-619 alone.

Other participants will receive a combination of CLN-619 with pembrolizumab. Early studies suggest this combination can further enhance the immune system's ability to find and destroy cancer cells. Pembrolizumab is already known to help the immune system attack tumors more effectively. Together, these treatments offer a promising approach for addressing advanced solid tumors. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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

My liver, kidneys, and blood counts are healthy.

My lung cancer is advanced and cannot be removed with surgery.

My treatment history matches the specific requirements for the trial's module.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Module E Safety Run-in and Expansion Experimental Treatment 2 Interventions

Patients with select NSCLC tumor types taking CLN-619 in combination with Dato-DXd

Group II: Module D Loading Dose Experimental Treatment 1 Intervention

Patients with select tumor types taking a loading dose of CLN-619

Group III: Module C Escalation and Expansion Experimental Treatment 4 Interventions

Patients with select tumor types taking CLN-619 in combination with chemotherapy

Group IV: 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 V: 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 VI: Module A Dose Escalation Experimental Treatment 1 Intervention

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

Group VII: 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+

Published Research Related to This Trial

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]

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]

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) 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 (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]

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, 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05117476

NCT05117476 | A Study of CLN-619 Alone and in ... CLN-619-001 is a Phase 1, open-label, multi-center study of CLN-619 alone and in combination with pembrolizumab in patients with advanced solid tumors.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2588

Cln-619 (anti-MICA/B antibody) alone and in combination ... Cln-619 (anti-MICA/B antibody) alone and in combination with pembrolizumab (P) for advanced solid tumors: Updated results of a Ph1 study.

3. targetedonc.com targetedonc.com/view/pushing-cln-619-forward-for-the-treatment-of-advanced-gynecologic-malignancies

Pushing CLN-619 Forward for the Treatment of Advanced ... CLN-619 has emerged for the treatment of advanced solid tumors in the clinical trial setting. Early results are promising, ...

4. cullinantherapeutics.com cullinantherapeutics.com/wp-content/uploads/2023/06/CLN-619-ASCO-2023-Poster-Final-Layout-5-17-23.pdf

A Phase 1 Dose-Escalation Study to Investigate the Safety, ... CLN-619 is a human IgG1 antibody that binds to and prevents proteolytic cleavage of NKG2D ligands MICA and MICB from tumor cells, thereby increasing tumor cell ...

5. biospace.com biospace.com/cullinan-therapeutics-to-present-clinical-data-from-phase-1-study-evaluating-novel-anti-mica-b-antibody-cln-619-as-monotherapy-and-in-combination-with-a-checkpoint-inhibitor-in-patients-with-advanced-solid-tumors-at-asco-2024

Cullinan Therapeutics to Present Clinical Data from Phase ... The data will include first results from the dose escalation cohort of CLN-619 in combination with checkpoint inhibitor pembrolizumab and ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.2532

A phase 1 dose-escalation study to investigate the safety, ... A phase 1 dose-escalation study to investigate the safety, efficacy, pharmacokinetics, and pharmacodynamic activity of cln-619 (Anti-MICA/B ...

7. onclive.com onclive.com/view/dr-moreno-on-the-pharmacodynamics-of-cln-619-in-advanced-solid-tumors

Dr Moreno on the Pharmacodynamics of CLN-619 in ... Prior data showed that both the monotherapy and combination regimens demonstrated safety and elicited objective responses. The pharmacodynamic ...