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Trial record 3 of 18 for:    exon 20 mutations | Recruiting, Not yet recruiting Studies | NSCLC

A Phase 1/2a Trial of CLN-081 in Patients With Non-Small Cell Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04036682
Recruitment Status : Recruiting
First Posted : July 30, 2019
Last Update Posted : October 19, 2020
Sponsor:
Information provided by (Responsible Party):
Cullinan Oncology, LLC ( Cullinan Pearl )

Brief Summary:
CLN-081-101 is a Phase 1/2a, open label, multi-center study of CLN-081 in patients with NSCLC (non small cell lung cancer) harboring EGFR (epidermal growth factor receptor) exon 20 insertion mutations, to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), as well as to evaluate preliminary efficacy.

Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer EGFR Exon 20 Mutation Drug: CLN-081 Phase 1 Phase 2

Detailed Description:

This is a Phase 1/2a, open-label, multicenter, first-in-human trial to evaluate the safety and tolerability, PK, PD, and preliminary efficacy of CLN-081 in patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion mutations.

This trial is divided into three parts: Phase 1 Dose Escalation, Phase 1 Dose Expansion, and Phase 2a Dose Expansion.

The objectives of the dose escalation part are to determine the safety, tolerability, MTD, recommended Phase 2 dose (RP2D), and to evaluate the anti-tumor activity of orally administered CLN-081 monotherapy. Additional objectives are to determine the pharmacokinetic (PK) profile of CLN-081 and CLN-081's activity in patients with known central nervous system (CNS) disease.

CLN-081 will be dosed once daily (QD) and twice daily (BID).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2a, Open-Label, Multi-Center Trial to Assess Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of CLN-081 in Patients With Non-Small Cell Lung Cancer Harboring EGFR Exon 20 Insertion Mutations
Actual Study Start Date : October 31, 2019
Estimated Primary Completion Date : September 15, 2021
Estimated Study Completion Date : March 15, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Phase 1 Dose Escalation (Accelerated Titration)
CLN-081 BID in single patient dose escalation cohorts enrolling NSCLC patients with EGFR exon 20 insertion mutations that either have received or never received prior EGFR TKIs.
Drug: CLN-081
CLN-081 tablets
Other Name: TAS6417

Experimental: Phase 1 Dose Escalation (Rolling Six)
CLN-081 QD or BID in Rolling Six dose escalation cohorts enrolling NSCLC patients with EGFR exon 20 insertion mutations.
Drug: CLN-081
CLN-081 tablets
Other Name: TAS6417

Experimental: Phase 1 Dose Expansion(s)
CLN-081 BID in expansion cohorts that may be opened at doses that meet pre-specified efficacy and safety criteria in Rolling Six cohorts.
Drug: CLN-081
CLN-081 tablets
Other Name: TAS6417

Experimental: Phase 2a Dose Expansion(s)
CLN-081 QD or BID in expansion cohorts that may be opened at doses that meet pre-specified efficacy and safety criteria in Phase 1 Dose Escalation cohorts.
Drug: CLN-081
CLN-081 tablets
Other Name: TAS6417




Primary Outcome Measures :
  1. All Cohorts: The rate and severity of treatment emergent AEs. [ Time Frame: 24 months ]
  2. All Cohorts: The rate and severity of DLTs. [ Time Frame: 24 months ]
  3. All Cohorts: Incidence of safety laboratory assessment abnormalities. [ Time Frame: 24 months ]
  4. All Cohorts: Incidence of abnormalities in vital signs. [ Time Frame: 24 months ]
  5. Phase 2a Dose Expansion Cohorts: Overall response rate (ORR) [ Time Frame: 24 months ]

Secondary Outcome Measures :
  1. Phase 1 Dose Escalation and Dose Expansion Cohorts: ORR [ Time Frame: 24 months ]
  2. Phase 1 Dose Escalation and Dose Expansion Cohorts: DOR (duration of response). [ Time Frame: 24 months ]
  3. Phase 1 Dose Escalation and Dose Expansion Cohorts: DCR (disease control rate) [ Time Frame: 24 months ]
  4. Phase 1 Dose Escalation and Dose Expansion Cohorts: PFS (progression free survival) [ Time Frame: 24 months ]
  5. Phase 1 Dose Escalation and Dose Expansion Cohorts: OS (overall survival) [ Time Frame: 24 months ]
  6. All Cohorts: Assessment of maximum concentration (Cmax) [ Time Frame: 24 months ]
  7. All Cohorts: Assessment of area under curve (AUC) [ Time Frame: 24 months ]
  8. All Cohorts: Assessment of time to maximum concentration (tmax) [ Time Frame: 24 months ]
  9. All Cohorts: Assessment of terminal half-life (t1/2) [ Time Frame: 24 months ]
  10. All Cohorts: Assessment of mean residence time (MRT) [ Time Frame: 24 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically or cytologically confirmed recurrent, metastatic NSCLC.
  2. Documented EGFR exon 20 insertion mutation demonstrated by a test routinely used by each institution and performed in a CLIA-certified or equivalent laboratory.
  3. Prior treatment in the recurrent/metastatic disease setting including:

    1. A platinum-based chemotherapy regimen (or other chemotherapy regimen if platinum-based chemotherapy is contra-indicated)
    2. 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.
  4. Measurable disease by RECIST 1.1.
  5. Age ≥ 18 years.
  6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
  7. Ability to take pills by mouth.
  8. Have the following laboratory values:

    1. Serum creatinine < 1.5 × ULN or if higher than normal range, calculated creatinine clearance (CrCl) must be ≥ 50 mL/min/1.73 m2 (by Cockroft-Gault formula); actual body weight must be used for CrCl unless BMI > 30 kg/m2 then lean body weight must be used.
    2. Total bilirubin ≤ 1.5 × ULN unless prior history of Gilbert's syndrome.
    3. Aspartate transaminase and alanine transaminase ≤ 2.5 × ULN, or ≤ 5 × ULN if due to liver involvement by tumor.
    4. Hemoglobin ≥ 9.0 g/dL.
    5. Platelets ≥ 100 × 109 cells/L.
    6. Absolute neutrophil count ≥ 1.5 ×109 cells/L.
  9. Ability to understand and the willingness to sign a written informed consent document and comply with study procedures.

Exclusion Criteria:

  1. Prior Exon 20 Patients Only

    a. No Prior treatment with an EGFR exon 20 insertion-targeting drug (e.g., poziotinib, TAK788, tarloxotinib, JNJ-61186372).

  2. Rolling Six, Phase 1 Expansion, and Phase 2a Expansion Patients Only

    a. Prior treatment with an EGFR exon 20 insertion-targeting drug (e.g., poziotinib, TAK788, tarloxotinib, JNJ-61186372).

  3. All Patients

    Treatment with any of the following:

    1. An EGFR tyrosine kinase inhibitors (TKIs) ≤ 8 days or 5x the terminal phase elimination half-lives, whichever is longer, prior to the first dose of study drug on C1D1
    2. Systemic anticancer treatment (excluding EGFR-TKIs as described above) ≤ 14 days prior to the first dose of study drug on C1D1.
    3. Radiotherapy < 28 days and palliative radiation ≤ 14 days prior to the first dose of study drug on C1D1. If irradiated, lesions must have demonstrated clear-cut progression prior to to being eligible for evaluation as target lesions.
    4. Immunotherapy ≤ 28 days prior to the first dose of study drug on C1D1.
    5. Major surgery (excluding placement of vascular access) ≤ 28 days of the first dose of study drug on C1D1.
  4. Have any unresolved toxicity of Grade ≥ 2 from previous anti-cancer treatment, except for alopecia and skin pigmentation. Patients with chronic, but stable Grade 2 toxicities may be allowed to enroll after agreement between the Investigator and Sponsor.
  5. Have known or suspected brain metastases or spinal cord compression, unless the condition has been asymptomatic, treated with surgery and/or radiation, and has been stable without requiring escalating corticosteroids or anti-convulsant medications for at least four weeks prior to the first dose of study drug on C1D1.
  6. Prior therapy with CLN-081.
  7. Known hypersensitivity to CLN-081 or any drugs similar in structure or class.
  8. Cardiac conditions as follows: Patient has a history of congestive heart failure (CHF) Class III/IV according to the New York Heart Association (NYHA) Functional Classification or serious cardiac arrhythmias requiring treatment.
  9. Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
  10. Resting corrected QT interval (QTc) > 470 msec.
  11. Patient is unable to take drugs orally due to disorders or diseases that may affect gastrointestinal function, such as inflammatory bowel diseases (e.g., Crohn's disease, ulcerative colitis) or malabsorption syndrome, or procedures that may affect gastrointestinal function, such as gastrectomy, enterectomy, or colectomy.
  12. Have any condition or illness that, in the opinion of the investigator, might compromise patient safety or interfere with the evaluation of the safety of the drug.
  13. Pregnant or lactating women; women of child-bearing potential (WOCBP) must have a negative serum pregnancy test ≤ 7 days prior to receiving study drug on C1D1. WOCBP and males with partners of child-bearing potential must agree to use adequate birth control throughout their participation and for six months following the last dose of study treatment.
  14. History of another primary malignancy ≤ 2 years prior to starting study drug on C1D1, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ.
  15. Uncontrolled intercurrent illness including, but not limited to, uncompensated respiratory, cardiac, hepatic, or renal disease, active infection (including HIV and active clinical tuberculosis), or renal transplant; ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, or psychiatric illness/social situations that would limit compliance with study requirements.
  16. For patients with a history of hepatitis B, active infection as defined by a positive HBsAg test and detectable HBV DNA. Patients ineligible due to detectable levels of HBV DNA at baseline may be rescreened for enrollment if their HBV DNA levels become undetectable after treatment with antiviral agents, and upon agreement between the investigator and Sponsor.
  17. For patients with a history of hepatitis C, active infection as defined by a reactive HCV antibody test and detectable HCV RNA.
  18. Active bleeding disorders.
  19. Is, in the Investigator's opinion, unable or unwilling to comply with the trial procedures.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04036682


Contacts
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Contact: Myles Clancy 617-410-4650 CLN081001trial@cullinanoncology.com

Locations
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United States, California
City of Hope Comprehensive Cancer Center Recruiting
Duarte, California, United States, 91010
Contact: Tiffani Gosha       tgosha@coh.org   
Principal Investigator: Marianna Koczywas, MD         
Pacific Shores Medical Group Recruiting
Long Beach, California, United States, 90813
Contact: Christina Hamilton    562-590-0345 ext 380    christinah@pacshoresoncology.com   
Principal Investigator: Danny Nguyen, MD         
United States, Florida
AdventHealth Not yet recruiting
Orlando, Florida, United States, 32804
Principal Investigator: Mark Socinski, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Zosia Piotrowska, MD         
Contact       zofia.piotrowska@mgh.harvard.edu   
Principal Investigator: Zosia Piotrowska, MD         
United States, New York
New York University Langone Health Recruiting
New York, New York, United States, 10016
Contact: Marjara Begum       Marjana.begum@nyulangone.org   
Principal Investigator: Vamsi Velcheti, MD         
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Helena Yu, MD    646-608-3912    YuH@mskcc.org   
Contact: Greg Reily, MD, PhD    646-888-4199    rielyg@mskcc.org   
Principal Investigator: Helena Yu, MD         
Sub-Investigator: Greg Riely, MD, PhD         
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Kristina Godwin       woodrufk@musc.edu   
Contact: Alex Leitner       leitnera@musc.edu   
Principal Investigator: John Wrangle, MD         
United States, Virginia
Virginia Cancer Specialists Recruiting
Fairfax, Virginia, United States, 22031
Principal Investigator: Alex Spira, MD, PhD         
China, Guangdong
Sun Yat Sen University Cancer Center Not yet recruiting
Guangzhou, Guangdong, China, 510060
Principal Investigator: Zheng Li, MD         
Hong Kong University - Shenzhen Hospital Not yet recruiting
Shenzhen, Guangdong, China, 518057
Principal Investigator: Victor Ho-Fun Lee, MBBS         
Hong Kong
Hong Kong University - Queen Mary Hospital Recruiting
Hong Kong, Hong Kong
Contact: Victor Ho-Fun Lee, MBBS       vhflee@hku.hk   
Principal Investigator: Victor Ho-Fun Lee, MBBS         
Netherlands
The Netherlands Cancer Institute (NKI) Recruiting
Amsterdam, Netherlands, 1066 CX
Contact: Egbert Smit, MD, PhD         
Contact       e.smit@nki.nl   
Principal Investigator: Egbert Smit, MD, PhD         
Singapore
Singapore Clinical Research Institute Recruiting
Singapore, Singapore, 138669
Contact: Mei Yan       mei_yan_pang@nuhs.edu.sg   
Principal Investigator: Ross Soo, MBBS         
National Cancer Centre Singapore Recruiting
Singapore, Singapore, 169610
Contact: Daniel Tan SW, MBBS, PhD       clinical.trials@nccs.com.sg   
Sub-Investigator: Daniel Tan SW, MBBS, PhD         
Taiwan
Taichung Veterans General Hospital Withdrawn
Taichung, Taiwan, 40705
National Taiwan University Hospital Recruiting
Taipei, Taiwan, 10002
Principal Investigator: James Chin-Hsin Yang, MD         
Sponsors and Collaborators
Cullinan Pearl
Investigators
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Study Chair: Zosia Piotrowska, MD Massachusetts General Hospital
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Responsible Party: Cullinan Pearl
ClinicalTrials.gov Identifier: NCT04036682    
Other Study ID Numbers: CLN-081-001
First Posted: July 30, 2019    Key Record Dates
Last Update Posted: October 19, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Cullinan Oncology, LLC ( Cullinan Pearl ):
NSCLC
EGFR
Exon 20 insertions
CLN-081
TAS6417
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms