Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 3 of 13 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 : Not yet recruiting
First Posted : July 30, 2019
Last Update Posted : October 1, 2019
Sponsor:
Information provided by (Responsible Party):
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).


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 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
Estimated 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

MedlinePlus related topics: Lung Cancer

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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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 may be demonstrated by:

    1. An FDA-approved device including cobas EGFR Mutation Test v2, therascreen EGFR RGQ PCR Kit, FoundationOne CDx, or MSK-IMPACT, or
    2. A device or test validated and accepted by regulatory health authorities outside the United States for patients enrolled in the trial outside of the United States.
  3. At least one prior treatment with platinum-based chemotherapy. Note: Prior treatment with a PD-1/PD-L1 inhibitor is allowed but not required.
  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.

Exclusion Criteria:

  1. Accelerated Titration Patients Only

    a. Any EGFR tyrosine kinase inhibitors (TKIs), e.g., gefitinib, erlotinib, afatinib, and osmertinib, ≤ 8 days or 5x the terminal phase elimination half-lives, whichever is longer, prior to the first dose of study drug on C1D1.

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

    Prior treatment with any of the following:

    1. An EGFR-TKI of > 6 months in which the patient derived clinical benefit.
    2. An EGFR exon 20 insertion-targeting drug (e.g., poziotinib, TAK788) for > 2 cycles or discontinuation due to progressive disease.

    Note: Patients that discontinued an EGFR 20 insertion-targeting inhibitor for other reasons (e.g, intolerability) and have received ≤ 2 cycles of treatment may not be excluded upon agreement between the Investigator and Sponsor.

  3. All Patients

    Treatment with any of the following:

    1. Systemic anticancer treatment (excluding EGFR-TKIs as described above) ≤ 14 days prior to the first dose of study drug on C1D1.
    2. Limited-field radiotherapy ≤ 7 days or extended-field thoracic radiotherapy < 4 weeks of study drug on C1D1.
    3. Major surgery (excluding placement of vascular access) ≤ 4 weeks 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.
  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. Mean resting corrected QT interval (QTc) > 470 msec obtained from three electrocardiograms (ECGs).
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. Uncontrolled intercurrent illness including, but not limited to, uncompensated respiratory, cardiac, hepatic, or renal disease, active infection (including hepatitis B, hepatitis C, 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.
  15. Active bleeding disorders.
  16. 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
Layout table for location contacts
Contact: Myles Clancy 617-410-4650 CLN081001trial@cullinanoncology.com

Locations
Layout table for location information
United States, California
City of Hope Comprehensive Cancer Center Not yet recruiting
Duarte, California, United States, 91010
United States, Massachusetts
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02114
United States, New York
Memorial Sloan Kettering Cancer Center Not yet recruiting
New York, New York, United States, 10065
Sponsors and Collaborators
Cullinan Pearl
Investigators
Layout table for investigator information
Study Chair: Zofia Piotrowska, MD Massachusetts General Hospital

Layout table for additonal information
Responsible Party: Cullinan Pearl
ClinicalTrials.gov Identifier: NCT04036682     History of Changes
Other Study ID Numbers: CLN-081-001
First Posted: July 30, 2019    Key Record Dates
Last Update Posted: October 1, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Cullinan Pearl:
NSCLC
EGFR
Exon 20 insertions
CLN-081
TAS6417
Additional relevant MeSH terms:
Layout table for MeSH terms
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