CLN-617 Alone and in Combination With Pembrolizumab in Patients With Advanced Solid Tumors

NCT06035744 | Recruiting Phase 1 FDA Drug

• 1 other identifier: CLN-617-001
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 5

Brief Summary

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

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (7)

• Dose Escalation

  Number of treatment-emergent events (TEAEs): TEAE is defined as adverse events reported for the first time or worsening of a pre-existing event after the first dose of study drug.

  24 Months

• Dose Optimization

  Number of treatment-emergent events (TEAEs): TEAE is defined as adverse events reported for the first time or worsening of a pre-existing event after the first dose of study drug.

  24 Months

• Dose Expansion

  Overall Response Rate (ORR): The % of patients having a CR or PR as determined by PI assessment of disease response per iRECIST

  24 Months

• Dose Expansion

  Duration of Response (DoR): The time from the earliest date of CR or PR until the earliest date of disease progression, as determined by PI assessment of disease response per iRECIST or death from any cause if occurring sooner than progression

  24 Months

• Dose Expansion

  Disease Control Rate (DCR): The % of participants having CR, PR, or SD as best on study response

  24 Months

• Dose Expansion

  Progression Free Survival (PFS): Time from initiate date of treatment to disease progression or death

  24 Months

• Dose Expansion

  Overall Survival (OS): Time from the initial date of treatment until death

  24 Months

Secondary Outcomes (6)

• All Cohorts

  24 Months

• All Cohorts

  24 Months

• All Cohorts

  24 Months

• All Cohorts

  24 Months

• All Cohorts

  24 Months

Study Arms (3)

CLN-617 Dose Escalation (Part A)

EXPERIMENTAL

Patients with Advanced Solid Tumors enrolled in dose escalation cohorts treated with CLN-617 alone and in combination with pembrolizumab

Drug: CLN-617; Drug: Pembrolizumab

CLN-617 Dose Optimization (Part B)

EXPERIMENTAL

Patients with Advanced Solid Tumors enrolled in dose optimization receiving selected doses of CLN-617 in combination with pembrolizumab

Drug: CLN-617; Drug: Pembrolizumab

CLN-617 Dose Expansion (Part C)

EXPERIMENTAL

Patients with Advanced Melanoma or Head and Neck Squamous Cell Carcinoma (HNSCC) enrolled in dose expansion treated with CLN-617 in combination with pembrolizumab

Drug: CLN-617; Drug: Pembrolizumab

Interventions

CLN-617 DRUG

Single-chain fusion protein comprised of human IL-2, human LAIR2, HSA, and human IL-12, connected via glycine/serine linker sequences

CLN-617 Dose Escalation (Part A); CLN-617 Dose Expansion (Part C); CLN-617 Dose Optimization (Part B)

Pembrolizumab DRUG

Humanized IgG4 anti-PD-1 monoclonal antibody

Also known as: Keytruda

CLN-617 Dose Escalation (Part A); CLN-617 Dose Expansion (Part C); CLN-617 Dose Optimization (Part B)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥ 18 years.
• Patient should have previously received or had a contraindication to standard therapy that confers an overall survival benefit.
• Part 1 Dose Escalation Cohorts: Histologically or cytologically confirmed advanced incurable or metastatic non-neurological solid tumor with accessible injectable lesions.
• Part 2 Dose Optimization: Histologically or cytologically confirmed select advanced incurable or metastatic cancer types with accessible injectable lesions.
• Part 3 Dose Expansions:
• Cohort 1: Histologically or cytologically confirmed metastatic or locally advanced, unresectable melanoma with accessible injectable lesions.
• Cohort 2: Histologically or cytologically confirmed metastatic or locally advanced, unresectable HNSCC with accessible injectable lesions.
• Patients must have 2 or more measurable lesions for Part 1, or one or more measurable lesions for Part 2 and Part 3 that meet RECIST v1.1. Also, patients must have tumors able to be palpable, visualized on ultrasound without encasing with blood vessels, amenable to direct injection.
• Patients deemed appropriate for pembrolizumab treatment based on the tumor type and prior available therapy, per the judgment of the investigator.
• Performance status of 0 or 1 based on the Eastern Cooperative Oncology Group (ECOG) performance scale.
• Estimated life expectancy at least 12 weeks or longer.
• Toxicities related to prior study therapy should have resolved to Grade 1 or less according to criteria of NCI CTCAE v5.0, except for alopecia. Patients with chronic but stable Grade 2 toxicities may be allowed to enroll after an agreement between the Investigator and Sponsor.
• Have adequate liver and kidney function and hematological parameters within a normal range as defined by:
• Total bilirubin ≤ 1.5x ULN. This does not apply for patients with confirmed Gilbert's Syndrome, for whom total bilirubin must be less than 3.0 mg/dL with a conjugated bilirubin less than 0.5 mg/dL.
• AST and ALT ≤ 2.5x ULN or ≤ 5x ULN for patients with liver metastases.

You may not qualify if:

• Patients with concomitant second malignancies (except adequately treated non-melanomatous skin cancers, ductal carcinoma in situ, superficial bladder cancer, prostate cancer, or in situ cervical cancer) are excluded unless in complete remission two years prior to study entry, and no additional therapy is required or anticipated to be required during study participation.
• Patients with any active autoimmune disease or a history of known autoimmune disease, or history of a syndrome that requires systemic corticosteroids or immunosuppressive medications, except for patients with vitiligo, resolved childhood asthma/atopy, or autoimmune thyroid disorders on stable thyroid hormone supplementation.
• 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:
• Uncontrolled airway hyper-reactivity.
• Type 1 diabetes mellitus. Type 2 diabetes mellitus patients are allowed if they are under stable glycemic control as per Investigator's assessment.
• Uncontrolled, clinically significant pulmonary disease.
• Requirement for supplemental oxygen to maintain SpO2 \> 93%.
• Symptomatic congestive heart failure as per Investigator's assessment or documented cardiac ejection fraction \< 45%.
• QT interval corrected for heart rate using Fridericia's formula (QTcF) of ≥ 470 milliseconds.
• History of unstable angina or myocardial infarction within six months of dosing on C1D1.
• Unstable cardiac arrhythmia.
• History of ventricular arrhythmia that requires medical treatment.
• Uncontrolled hypertension: patients with sustained systolic blood pressure readings greater than 150 mmHg or diastolic blood pressure greater than 100 mmHg should have documentation by the treating physician that the finding is not consistent with uncontrolled hypertension.
• History of stroke or cerebral hemorrhage within one year of dosing on C1D1.
• Poorly controlled seizure disorder.

Sponsors & Collaborators

• Cullinan Therapeutics Inc.: lead

Study Sites (5)

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

NOT YET RECRUITING

Orlando Health

Orlando, Florida, 32806, United States

RECRUITING

University of Chicago

Chicago, Illinois, 60637, United States

NOT YET RECRUITING

MD Anderson

Houston, Texas, 77030, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

Related Publications (1)

• Mehta NK, Rakhra K, Meetze KA, Li B, Momin N, Chang JYH, Wittrup KD, Baeuerle PA, Michaelson JS. CLN-617 Retains IL2 and IL12 in Injected Tumors to Drive Robust and Systemic Immune-Mediated Antitumor Activity. Cancer Immunol Res. 2024 Aug 1;12(8):1022-1038. doi: 10.1158/2326-6066.CIR-23-0636.

  PMID: 38842347 DERIVED

MeSH Terms

Interventions

pembrolizumab

Central Study Contacts

Shane McLoughlin

CONTACT

6178609878; ClinOps@cullinanoncology.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2023
• First Posted: September 13, 2023
• Study Start: December 12, 2023
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: March 3, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)