A Study of CLN-619 Alone and in Combination With Pembrolizumab in Advanced Solid Tumors

NCT05117476 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: CLN-619-001
• Study Type: interventional
• Target: 440
• Locations: 4 countries
• Sites: 24

Brief Summary

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.

Conditions

Advanced Solid Tumor; NSCLC

Keywords

NSCLC; CLN-619; MICA

Outcome Measures

Primary Outcomes (7)

• Dose Escalation: TEAEs

  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: Best Overall Response (BOR)

  The percentage of patients having a CR or PR as determined by PI assessment of disease response per RECIST 1.1 on at least one scan.

  Every 6 weeks for the first 18 weeks and then every 9 weeks until disease progression; approximately 36 months

• Dose Expansion: Overall Response Rate (ORR)

  The percentage of patients having a CR or PR as determined by PI assessment of disease response per RECIST 1.1.

  Every 6 weeks for the first 18 weeks and then every 9 weeks until disease progression; approximately 36 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 RECIST 1.1 or death from any cause if occurring sooner than progression.

  Every 6 weeks for the first 18 weeks and then every 9 weeks until disease progression; approximately 36 months

• Dose Expansion: Disease Control Rate (DCR)

  The percentage of participants having CR, PR, or SD as best on study response.

  Every 6 weeks for the first 18 weeks and then every 9 weeks until disease progression; approximately 36 months

• Dose Expansion: Overall Survival (OS)

  Time from the initial date of treatment until death.

  Every 6 weeks for the first 18 weeks and then every 9 weeks until disease progression; approximately 36 months

• Dose Expansion: Clinical Benefit Rate (CBR)

  The percentage of participants who achieve CR, PR or SD for a duration of 6 months as determined by PI assessment of disease response per RECIST 1.1.

  Every 6 weeks for the first 18 weeks and then every 9 weeks until disease progression; approximately 36 months

Secondary Outcomes (7)

• All Cohorts: Cmax

  Up to 2 years

• All Cohorts: AUC

  Up to 2 years

• All Cohorts: Time to Maximum concentration

  Up to 2 years

• All Cohorts: Clast

  Up to 2 years

• All Cohorts: Time to last plasma concentration

  Up to 2 years

Study Arms (7)

Module A Dose Escalation

EXPERIMENTAL

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

Drug: CLN-619

Module A Cohort Expansion

EXPERIMENTAL

Patients with select solid tumor types enrolled in expansion cohorts treated with CLN-619 at a dose selected from the Module A Escalation arm

Drug: CLN-619

Module B Combination Therapy Dose Escalation

EXPERIMENTAL

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

Drug: CLN-619; Drug: Pembrolizumab

Module B Combination Therapy Cohort Expansion

EXPERIMENTAL

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

Drug: CLN-619; Drug: Pembrolizumab

Module C Escalation and Expansion

EXPERIMENTAL

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

Drug: CLN-619; Drug: Paclitaxel; Drug: Carboplatin AUC 6; Drug: pemetrexed

Module D Loading Dose

EXPERIMENTAL

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

Drug: CLN-619

Module E Safety Run-in and Expansion

EXPERIMENTAL

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

Drug: CLN-619; Drug: Datopotamab deruxtecan-dlnk (Dato-DXd)

Interventions

CLN-619 DRUG

Anti-MICA/MICB monoclonal antibody

Module A Cohort Expansion; Module A Dose Escalation; Module B Combination Therapy Cohort Expansion; Module B Combination Therapy Dose Escalation; Module C Escalation and Expansion; Module D Loading Dose; Module E Safety Run-in and Expansion

Pembrolizumab DRUG

Keytruda

Module B Combination Therapy Cohort Expansion; Module B Combination Therapy Dose Escalation

Paclitaxel DRUG

Taxane

Module C Escalation and Expansion

Carboplatin AUC 6 DRUG

Platinum compound

Module C Escalation and Expansion

pemetrexed DRUG

antifolate

Module C Escalation and Expansion

Datopotamab deruxtecan-dlnk (Dato-DXd) DRUG

TROP-2 antibody-drug conjugate (ADC)

Module E Safety Run-in and Expansion

Eligibility Criteria

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

You may qualify if:

• Males or females aged ≥ 18 years.
• Willing and able to give written informed consent and adhere to protocol requirements; written informed consent and any locally required authorization must be obtained from the patient prior to performing any protocol-related procedures, including screening evaluations.
• Module A Monotherapy Dose Escalation Cohort and Module B Combination Therapy Dose Escalation Cohorts: Histologically or cytologically-confirmed metastatic or locally advanced, unresectable solid tumors. For Module B, tumor type is listed as an approved indication per the current prescribing information for pembrolizumab.
• Module A Cohort Expansions:
• Expansion A1: Histologically or cytologically-confirmed metastatic or locally advanced, unresectable NSCLC;
• Expansion A2: Histologically or cytologically-confirmed metastatic or locally advanced, unresectable cervical cancer.
• Expansion A3 and A4: Histologically or cytologically-confirmed metastatic or locally advanced, unresectable endometrial cancer.
• Eligibility for disease-specific expansion cohorts may be further refined by histologic subtype, molecular features, or exposure to prior therapy based on clinical, pharmacodynamic, or biomarker data emerging from the study.
• Module B Cohort Expansions:
• Expansion B1: Histologically or cytologically-confirmed metastatic or locally-advanced, unresectable NSCLC.
• Expansion B2: Histologically or cytologically-confirmed metastatic or locally-advanced, unresectable endometrial.
• Eligibility for disease-specific expansion cohorts may be further refined by histologic subtype, molecular features, or exposure to prior therapy based on clinical, pharmacodynamic, or biomarker data emerging from the study.
• Module C CLN-619 + Chemotherapy Combination Therapy, Escalation and Expansion Cohort
• C1: Histologically or cytologically confirmed metastatic or locally advanced, unresectable EGFRm NSCLC.
• C2: Histologically or cytologically confirmed metastatic or locally advanced, unresectable endometrial cancer.

You may not qualify if:

• Currently participating/previously participated in an interventional study and received an investigational drug within 28 days (or five half-lives, whichever is longer) of dosing on C1D1.
• 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 three 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 or suspected 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 assessment;
• Uncontrolled, clinically significant pulmonary disease;
• Requirement for supplemental oxygen to maintain a pulse ox \> 93%;
• Symptomatic congestive heart failure as per Investigator assessment or documented cardiac ejection fraction less than 45%;
• Ejection fraction \< 45% in patients with prior history of treatment with anthracycline chemotherapy or with a prior history of cardiac ventricular dysfunction;
• History of unstable angina or myocardial infarction within six months of dosing on C1D1;
• Unstable cardiac arrhythmia;
• History of ventricular arrhythmia;
• Uncontrolled hypertension: patients with sustained systolic blood pressure readings greater than 150 or diastolic blood pressure greater than 100 should have documentation by treating physician that the finding is not consistent with uncontrolled hypertension;
• History of stroke or cerebral hemorrhage within one year of dosing on C1D1;

Sponsors & Collaborators

• Cullinan Therapeutics Inc.: lead

Study Sites (24)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

City of Hope

Irvine, California, 92618, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

START Midwest

Grand Rapids, Michigan, 49546, United States

Location

Hackensack Meridian Health

Hackensack, New Jersey, 07601, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Carolina BioOncology Institute

Huntersville, North Carolina, 28078, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

START San Antonio

San Antonio, Texas, 78229, United States

Location

Virginia Cancer Center

Fairfax, Virginia, 22031, United States

Location

Monash Health

Clayton, Victoria, 3168, Australia

Location

Alfred Health

Melbourne, Victoria, 3004, Australia

Location

Linear Clinical Research

Nedlands, Western Australia, 6009, Australia

Location

Biokinetica

Józefów, 05-410, Poland

Location

Med-Polonia Sp. zo. o.

Poznan, 60-693, Poland

Location

Narodowy Insytut Onkologii im Marii Sklodowskiej-Curie

Warsaw, 02-781, Poland

Location

Hospital Universitario Insular de Gran Canaria

Las Palmas de Gran Canaria, Gran Canaria, 35016, Spain

Location

START Barcelona

Barcelona, 08023, Spain

Location

Hospital Clinic Barcelona

Barcelona, 08036, Spain

Location

START Madrid FJD

Madrid, 28040, Spain

Location

Clinica Universidad de Navarra

Pamplona, 31008, Spain

Location

Hospital Universitari Parc Tauli

Sabadell, 08208, Spain

Location

MeSH Terms

Interventions

pembrolizumab; Paclitaxel; Pemetrexed

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Design

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

Study Record Dates

• First Submitted: September 2, 2021
• First Posted: November 11, 2021
• Study Start: October 29, 2021
• Primary Completion: March 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: November 24, 2025

Record last verified: 2025-10

Locations

US (12); AU (3); ES (6); PL (3)