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Advanced Solid TumorPhase 1MICANCT05117476

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

A Phase 1 study testing CLN-619, Pembrolizumab and Paclitaxel in people with Advanced Solid Tumor and NSCLC, run by Cullinan Therapeutics Inc. at 24 sites in 4 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Solid Tumor, NSCLC
What is being tested?
CLN-619, Pembrolizumab and Paclitaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
440 participants
Where
24 sitesin 4 countries
Study dates
29 Oct 2021to Jun 2026
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • C3: Histologically or cytologically confirmed metastatic or locally advanced, unresectable, platinum-resistant epithelial ovarian cancer (including fallopian tube and primary peritoneal 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 D Loading Dose Cohort:
  • Tumor types are restricted to epithelial ovarian (including fallopian tube and primary peritoneal), breast, and gastrointestinal (esophageal, gastric, colorectal).
  • Module E CLN-619 + Dato-DXd Combination Therapy, Safety Run-in and Expansion Cohorts:
  • Histologically or cytologically confirmed recurrent metastatic or locally advanced, unresectable EGFRm NSCLC.
  • Local testing for determination of the mutation status is required.
  • Prior treatment history as follows:
  • Patients should have received any other approved standard therapy that is available to the patient, unless this therapy is contraindicated, intolerable to the patient, or is declined by the patient. In the case of a patient declining such therapy, documentation that the patient has been informed and declined should be documented in the medical record.
  • Patients eligible for Module E must meet the following criteria: Have received up to 4 prior lines of therapy, including i. Platinum-based chemotherapy ii. At least 1 EGFRm-directed targeted therapy iii. If EGFR T790M, must have received prior osimertinib iv. Prior treatment with topoisomerase I-targeted chemotherapeutic agent or TROP2-directed therapy not allowed
  • At baseline, patients are required to have one or more measurable lesions that meet RECIST v1.1 and meet the following conditions:
  • A non-lymph node lesion that has a longest unidimensional measurement of ≥ 10 mm or a lymph node lesion that has a shortest unidimensional measurement of ≥ 15 mm;
  • Lesions that have received previous local treatment, such as radiotherapy or ablation, can also be used as measurable target lesions if progression has been confirmed according to RECIST v1.1 prior to enrollment, and the longest unidimensional measurement is ≥ 10 mm.
  • Performance status of 0 or 1 based on the Eastern Cooperative Oncology Group (ECOG) performance scale.
  • Estimated life expectancy of 12 weeks or greater.
  • Prior palliative radiotherapy must have been completed 14 days prior to dosing on C1D1.
  • 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. Peripheral neuropathy should be clinically stable or improving and be Grade 2 or less in severity. Patients with chronic but stable Grade 2 toxicities may be allowed to enroll after 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;
  • Creatinine clearance (CrCl) ≥ 45 mL/min as measured or estimated using Cockcroft-Gault formula or serum creatinine < 1.5 x ULN;
  • Hemoglobin ≥ 9 g/dL without blood transfusions for at least two weeks prior to dosing on C1D1;
  • Absolute neutrophil count ≥ 1500 cells/mm3 without growth factor support, three days for filgrastim, 14 days for pegfilgrastim;
  • Platelet count ≥ 100,000 cells/mm3.
  • Patients in the Module A, B, and C dose-escalation cohorts and Module D must have archival tissue available for biomarker analysis. A fresh biopsy is required if archival tissue (e.g., all tumor blocks are exhausted) is unavailable.
  • Patients participating in the Module A or Module D dose-level cohort extension(s) must agree to provide a fresh biopsy and an on-treatment biopsy at Cycle 2, Day 8.
  • Patients in the expansion cohorts for Modules A, B, and C must agree to provide a fresh pretreatment biopsy and an on-treatment biopsy at Cycle 2, Day 8.
  • Patients participating in Module E safety run-in and expansion cohorts must provide archival tissue. Pre-treatment fresh biopsies are preferred but not required. On-treatment biopsies are not required.

Who cannot join

  • 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;
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  • 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;
  • Poorly controlled seizure disorder;
  • Active diverticulitis within one year prior to dosing on C1D1;
  • Recent major surgery within three months of dosing on C1D1 or major surgery with unresolved complications that could interfere with study treatment.
  • Clinically significant corneal disease (Module E).
  • Treatment with systemic antiviral, antibacterial or antifungal agents for acute infection within ≤ 7 days of dosing on C1D1.
  • Has known human immunodeficiency virus (HIV) infection that is not well controlled.
  • Diagnosed with hepatitis B (with positive testing for either hepatitis B surface antigen [HBsAg] or hepatitis B core Ab) or hepatitis C virus (HCV) infection (with positive testing for HCV antibody and/or HCV ribonucleic acid [RNA] in serum) under any of the following conditions:
  • Active disease for hepatitis B or hepatitis C and received antiretroviral therapy within 4 weeks.
  • Blood hepatitis B DNA or HCV RNA are detectable.
  • Prior organ allograft or allogeneic hematopoietic transplantation.
  • History of the following events in conjunction with prior treatment with checkpoint inhibitor immunotherapy: Grade 3 or greater neurotoxicity, ocular toxicity, pneumonitis, myocarditis, or colitis; liver dysfunction meeting the laboratory criteria for Hy's Law.
  • Symptomatic uncontrolled brain metastases, known or suspected leptomeningeal metastases and/or carcinomatous meningitis.
  • Receipt of live vaccine < 28 days prior to study start. Treatment with non-oncology recombinant or inactivated vaccines for the control of infectious diseases may be administered according to institutional policy.
  • Active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection based on positive SARS-CoV-2 testing or patients with suspected active infection based on clinical features, including patients with history of SARS-CoV-2-related pneumonitis with 28 days prior to enrollment or patients who have clinically significant pulmonary symptoms related to prior pneumonitis.
  • Has received immunosuppressive medications including but not limited to cellcept, methotrexate, infliximab, anakinra, tocilizumab, cyclosporine or corticosteroids (≥10 mg/day of prednisone or equivalent), within 14 days of dosing on C1D1.
  • Woman of child-bearing potential (WOCBP) who is pregnant or breast-feeding, plans to become pregnant within 120 days of last study drug administration, or declines to use an acceptable method to prevent pregnancy during study treatment and for 120 days after the last dose of study drug administration.
  • Male patient who plans to father a child or donate sperm within 120 days or 5 half-lives of CLN-619, whichever comes later, of last study drug administration, or who has a partner who is a WOCBP, and declines to use acceptable method to prevent pregnancy during study treatment and for 120 days or 5 half-lives of CLN-619, whichever comes later, after the last dose of study drug administration.
  • QT interval corrected for heart rate using Fridericia's formula (QTcF) of ≥ 500 milliseconds.
  • Patient has history of drug-related anaphylactic reactions to any components of CLN-619 or combination agent, including hypersensitivity of drugs with similar structure or class. History of Grade 4 anaphylactic reaction to any monoclonal antibody therapy.
  • Known active alcohol or drug abuse.
  • Inability to comply with the protocol and/or not willing or not available for follow-up assessments.
  • Patients who are incapacitated or involuntarily incarcerated.
  • Patients who are unsuitable for participation based on the judgement of the Investigator.
  • Treatment with any of the following:
  • Systemic anticancer treatment within 14 days prior to the first dose of study drug on C1D1.
  • Immunotherapy ≤ 28 days prior to the first dose of study drug on C1D1.
  • Systemic radiotherapy ≤28 days and local and palliative radiation ≤ 14 days prior to the first dose of study drug on C1D1. I
  • Major surgery (excluding placement of vascular access) ≤ 28 days of the first dose of study drug on C1D1.

Trial locations and contacts

24 sites in 4 countries.

24 sites in 4 countries

United States12 sites

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35233

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • City of Hope

    Duarte, California, 91010

  • Virginia Cancer Center

    Fairfax, Virginia, 22031

  • START Midwest

    Grand Rapids, Michigan, 49546

  • Hackensack Meridian Health

    Hackensack, New Jersey, 07601

  • Carolina BioOncology Institute

    Huntersville, North Carolina, 28078

  • City of Hope

    Irvine, California, 92618

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • START San Antonio

    San Antonio, Texas, 78229

  • Florida Cancer Specialists

    Sarasota, Florida, 34232

Other trials in United States

Spain6 sites

  • START Barcelona

    Barcelona, 08023

  • Hospital Clinic Barcelona

    Barcelona, 08036

  • Hospital Universitario Insular de Gran Canaria

    Las Palmas de Gran Canaria, Gran Canaria, 35016

  • START Madrid FJD

    Madrid, 28040

  • Clinica Universidad de Navarra

    Pamplona, 31008

  • Hospital Universitari Parc Tauli

    Sabadell, 08208

Other trials in Spain

Australia3 sites

  • Monash Health

    Clayton, Victoria, 3168

  • Alfred Health

    Melbourne, Victoria, 3004

  • Linear Clinical Research

    Nedlands, Western Australia, 6009

Other trials in Australia

Poland3 sites

  • Biokinetica

    Józefów, 05-410

  • Med-Polonia Sp. zo. o.

    Poznan, 60-693

  • Narodowy Insytut Onkologii im Marii Sklodowskiej-Curie

    Warsaw, 02-781

Other trials in Poland

About this study

Official title: A Phase 1 Dose-Escalation Study to Investigate the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamic Activity of CLN-619 (Anti-MICA/MICB Antibody) Alone and in Combination With Pembrolizumab in Patients With Advanced Solid Tumors

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.

Being tested
CLN-619, Pembrolizumab, Paclitaxel, Carboplatin AUC 6, pemetrexed
Keywords
NSCLC, CLN-619, MICA

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CLN-619Drug

    Anti-MICA/MICB monoclonal antibody

  • PembrolizumabDrug

    Keytruda

  • PaclitaxelDrug

    Taxane

  • Carboplatin AUC 6Drug

    Platinum compound

  • pemetrexedDrug

    antifolate

  • Datopotamab deruxtecan-dlnk (Dato-DXd)Drug

    TROP-2 antibody-drug conjugate (ADC)

Study groups in NCT05117476
Study groupRoleWhat they receive
Module A Dose EscalationExperimentalPatients with advanced solid tumors enrolled in dose escalation cohorts treated with CLN-619
Receives: Drug: CLN-619
Module A Cohort ExpansionExperimentalPatients with select solid tumor types enrolled in expansion cohorts treated with CLN-619 at a dose selected from the Module A Escalation arm
Receives: Drug: CLN-619
Module B Combination Therapy Dose EscalationExperimentalPatients with advanced solid tumors enrolled in dose escalation cohorts treated with CLN-619 in combination with pembrolizumab
Receives: Drug: CLN-619; Drug: Pembrolizumab
Module B Combination Therapy Cohort ExpansionExperimentalPatients 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
Receives: Drug: CLN-619; Drug: Pembrolizumab
Module C Escalation and ExpansionExperimentalPatients with select tumor types taking CLN-619 in combination with chemotherapy
Receives: Drug: CLN-619; Drug: Paclitaxel; Drug: Carboplatin AUC 6; Drug: pemetrexed
Module D Loading DoseExperimentalPatients with select tumor types taking a loading dose of CLN-619
Receives: Drug: CLN-619
Module E Safety Run-in and ExpansionExperimentalPatients with select NSCLC tumor types taking CLN-619 in combination with Dato-DXd
Receives: Drug: CLN-619; Drug: Datopotamab deruxtecan-dlnk (Dato-DXd)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 24 Months

  2. 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.

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

  3. 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.

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

  4. 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.

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

  5. Dose Expansion: Disease Control Rate (DCR)

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

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

  6. Dose Expansion: Overall Survival (OS)

    Time from the initial date of treatment until death.

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

  7. 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.

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

Secondary outcomes (7)

  1. All Cohorts: Cmax

    Maximum drug concentration (Cmax) of CLN-619

    Measured: Up to 2 years

  2. All Cohorts: AUC

    Area under the curve up to tau (AUCtau) of CLN-619

    Measured: Up to 2 years

  3. All Cohorts: Time to Maximum concentration

    Time to Cmax (Tmax) of CLN-619

    Measured: Up to 2 years

  4. All Cohorts: Clast

    Last validated plasma concentration (Clast) of CLN-619

    Measured: Up to 2 years

  5. All Cohorts: Time to last plasma concentration

    Time to Clast (Tlast) of CLN-619

    Measured: Up to 2 years

  6. All Cohorts: Half-life

    Terminal Half-life (t1/2) of CLN-619

    Measured: Up to 2 years

  7. All Cohorts: Volume of Distribution

    Volume of Distribution (V) of CLN-619

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Nov 2021
  2. Study start29 Oct 2021
  3. Primary completionMar 2026 (estimated)
  4. Study completionJun 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
440 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05117476
Sponsor's protocol ID
CLN-619-001
Acronym
MICA
Status last verified
Oct 2025
First submitted
2 Sep 2021
Last updated
24 Nov 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CLN-619, Pembrolizumab and Paclitaxel in people with Advanced Solid Tumor and NSCLC, run by Cullinan Therapeutics Inc. at 24 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 43 inclusion and 43 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 24 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in United States, Spain, Australia, Poland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Escalation: TEAEs (time frame: 24 Months). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05117476.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Nov 2025.

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