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Non Small Cell Lung CancerPhase 1/2REZILIENT1NCT04036682

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

A Phase 1/2 study testing CLN-081 in people with Non Small Cell Lung Cancer and EGFR Exon 20 Mutation, run by Cullinan Therapeutics Inc. at 64 sites in 9 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-081-001 is a Phase 1/2, open label, multi-center study of CLN-081 in patients with non-small cell lung cancer (NSCLC) harboring EGFR (epidermal growth factor receptor) exon 20 insertion mutations, to characterize the safety, determine the recommended Phase 2 dose (RP2D), and evaluate efficacy. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
CLN-081
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
284 participants
Where
64 sitesin 9 countries
Study dates
31 Oct 2019to 31 Mar 2028
Phase
Phase 1/2
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

  • Histologically or cytologically confirmed locally advanced or metastatic NSCLC (all patients).
  • Documented EGFR ex20ins mutation demonstrated by a validated test listed in Section 9.7 and performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified or equivalent laboratory (all patients other than Module A Food Effect PK Assessment Module). Institutions that don't have access to these tests should contact the sponsor for assistance.
  • Prior treatment in the recurrent/metastatic disease setting including:
  • A platinum-based chemotherapy regiment (or other chemotherapy regimen if platinum-based chemotherapy is contra-indicated)
  • 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.
  • No prior therapy is required for patients enrolled on Module A.
Show all 21Show fewer
  • Prior therapy with an agent approved by the local regulatory authorities for the treatment of EGFR ex20ins mutant NSCLC (Module C only).
  • Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) (except for patients enrolled on Module A).
  • Age ≥ 18 years.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
  • Ability to take pills by mouth.
  • Have the following laboratory values:
  • Serum creatinine < 1.5 × upper limit of normal (ULN) or calculated creatinine clearance (CrCl) must be ≥ 50 mL/min/1.73 m2 (if calculated by Cockroft-Gault formula, the actual body weight must be used for CrCl unless body mass index [BMI] >30 kg/m2 then lean body weight must be used).
  • Total bilirubin ≤ 1.5 × ULN unless prior history of Gilbert's syndrome.
  • AST and ALT ≤ 2.5 × ULN, or ≤ 5 × ULN if due to liver involvement by tumor.
  • Hemoglobin ≥ 9.0 g/dL in the absence of transfusion ≤ 14 days prior to the first dose of study drug on C1D1.
  • Platelets ≥ 100 × 109 cells/L in the absence of transfusion <14 days prior to the first dose of study drug on Cycle 1 Day 1 (C1D1).
  • Absolute neutrophil count ≥ 1.5 ×109 cells/L.
  • For Module A patients only: patients must have a negative coronavirus disease 2019 (COVID-19) polymerase chain reaction test prior to enrolment.
  • For Module B and Module C patients only: verification of suitable archived tumor tissue available at the participating center for biomarker analysis. A fresh biopsy is required if an archived sample is not available.
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • R6, Phase 1 Expansion, Phase 2a, Module A and Module B Patients Only
  • Prior treatment with an EGFR ex20ins -targeting drug (eg, including, but not limited to poziotinib, mobocertinib, amivantamab, DZD9008, BDTX-189).
  • Note: enrolment of patients treated previously with EGFR ex20ins-targeting drugs allowed selectively during accelerated titration dose escalation and Module C only.
  • Module A Food Effect PK Assessment Module patients only
  • Conditions that compromise esophageal or gastrointestinal (GI) function, including esophageal, gastric, pancreatic, hepatobiliary, or small bowel carcinomas, or history of gastric resection.
  • Recurrent diarrhea, nausea, or vomiting.
Show all 36Show fewer
  • Unable to refrain from or anticipates the use of:
  • Any drug, including prescription and non-prescription medications, including drugs that change gastrointestinal motility (eg, loperamide) or gastric pH (eg, antacids, H2 antagonists, proton pump inhibitors), herbal remedies, or vitamin supplements within 14 days prior to the first dosing on Day 1 to follow-up.
  • Any drugs known to be inhibitors or inducers of CYP3A enzymes and/or P-glycoprotein (P-gp), including St. John's Wort and grape fruit juice, within 28 days prior to the first dosing and throughout the PK assessment.
  • Any allergies to the composition of the high fat meal.
  • Patients who use tobacco products.
  • All Patients
  • History of COVID-19-related pneumonitis requiring hospitalization.
  • History of COVID-19 infection within 4 weeks prior to enrolment, or clinically significant pulmonary symptoms related to prior COVID-19 pneumonitis.
  • Treatment with any of the following:
  • An EGFR TKI ≤ 8 days or 5 × the terminal phase t1/2, whichever is longer, prior to the first dose of study drug on C1D1.
  • Systemic anticancer treatment (excluding EGFR-TKIs as described above) 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.
  • 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 being eligible for evaluation as target lesions.
  • Major surgery (excluding placement of vascular access) ≤ 28 days of the first dose of study drug on C1D1.
  • 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.
  • Have known or suspected leptomeningeal metastasis. Have known or suspected brain metastases or spinal cord compression, unless the condition has been asymptomatic, treated with surgery and/or radiation (if clinically indicated), 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.
  • Prior therapy with CLN-081.
  • Known hypersensitivity to CLN-081 or any drugs similar in structure or class.
  • Past medical history of interstitial lung disease, drug-induced interstitial lung disease, treatment-related pneumonitis, or any evidence of clinically active interstitial lung disease.
  • 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.
  • Resting QTcF > 470 msec.
  • Patient is unable to take drugs po due to disorders or diseases that may affect GI function, including but not limited to inflammatory bowel diseases (eg, Crohn's disease, ulcerative colitis) or malabsorption syndrome, or procedures that may affect gastrointestinal function, such as gastrectomy, enterectomy, or colectomy.
  • 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.
  • Pregnant or lactating females; females of child-bearing potential (FOCBP) must have a negative serum pregnancy test at within seven days prior to receiving study drug on C1D1. FOCBP and males with partners of child-bearing potential must agree to use adequate birth control (Section 16.3) throughout their participation and for six months following the last dose of study treatment.
  • History of another primary malignancy within 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.
  • Uncontrolled intercurrent illness including, but not limited to, uncompensated respiratory, cardiac, hepatic, or renal disease, active infection (including human immunodeficiency virus (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.
  • For patients with a history of hepatitis B (HBV), negative PCR test is required. Patients with active hepatitis B (HBV) infection [as defined by a positive hepatitis B serum antigen (HBsAg) test and detectable HBV deoxyribonucleic acid (DNA)]. Patients ineligible due to detectable levels of HBV DNA at baseline may be rescreened for enrolment if their HBV DNA levels become undetectable after treatment with antiviral agents, and upon agreement between the Investigator and Sponsor.
  • For patients with a history of hepatitis C, active infection as defined by a reactive hepatitis C virus (HCV) antibody test and detectable HCV ribonucleic acid (RNA).
  • Active bleeding disorders.
  • The patient is, in the Investigator's opinion, unable or unwilling to comply with the trial procedures.

Trial locations and contacts

64 sites in 9 countries.

64 sites in 9 countries

United States18 sites

  • Pacific Cancer Medical Center, Inc

    Anaheim, California, 92801

  • University of Michigan Health System - University Hospital

    Ann Arbor, Michigan, 48109

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Gabrail Cancer Center Research

    Canton, Ohio, 44701

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • Virginia Cancer Specialists

    Fairfax, Virginia, 22031

  • Summit Medical Group PA

    Florham Park, New Jersey, 07932

  • City of Hope at Irvine Lennar

    Irvine, California, 92618

  • Pacific Shores Medical Group

    Long Beach, California, 90813

  • Perlmutter Cancer Center at NYU Langone Hospital - Long Island

    Mineola, New York, 11501

  • New York University Langone Health

    New York, New York, 10016

  • Columbia University Irving Medical Center

    New York, New York, 10032

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • AdventHealth

    Orlando, Florida, 32804

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • Providence Cancer Center

    Portland, Oregon, 97213

  • Providence Oncology & Hematology Care Clinic-Westside

    Portland, Oregon, 97225

Other trials in United States

Spain13 sites

  • University Hospital A Coruna

    A Coruña

  • Hospital Clinic i Provincial de Barcelona

    Barcelona

  • Hospital Parc Tauli

    Barcelona

  • Hospital Universitario Vall d'Hebron

    Barcelona

  • Institut Catala d'Oncologia l'Hospitalet

    Barcelona

  • START Barcelona

    Barcelona

  • Complejo Hospitalario Universitario Insular Materno Infantil

    Las Palmas

  • Hospital General Universitario Gregorio Maranon (HGUGM)

    Madrid

  • Hospital Universitario Puerta de Hierro de Majadahonda

    Madrid

  • University Hospital Quironsalud Madrid

    Madrid

  • Hospital Regional Universitario de Malaga

    Málaga

  • Clinica Universidad de Navarra

    Pamplona

  • Universitat de Valencia - Hospital Universitari i Politecnic La Fe de Valencia (Hospital La Fe Bulevar Sur)

    Valencia

Other trials in Spain

South Korea9 sites

  • National Cancer Center

    Goyang-si

  • Seoul National University Bundang Hospital (SNUBH)

    Gyeonggi-do

  • Gachon University Gil Medical Center

    Incheon

  • Inha University Hospital

    Incheon

  • Samsung Medical Center

    Seoul

  • Asan Medical Center (AMC)

    Soeul

  • Korea University Guro Hospital

    Soeul

  • Ajou University Hospital

    Suwon

  • The Catholic University Of Korea St. Vincent's Hospital

    Suwon

Other trials in South Korea

Italy7 sites

  • Azienda Ospedaliero Universitaria Careggi

    Careggi

  • Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I

    Marche

  • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS

    Meldola

  • IRCCS-Istituto Europeo di Oncologia

    Milan

  • Azienda Ospedaliero Universitaria Modena

    Modena

  • San Gerardo Hospital

    Monza

  • Ospedale Santa Maria delle Croci

    Ravenna

Other trials in Italy

Japan7 sites

  • National Cancer Center Hospital East

    Chiba

  • Niigata Cancer Center

    Niigata

  • Osaka City General Hospital

    Osaka

  • Osaka International Cancer Institute

    Osaka

  • Shizuoka Cancer Center

    Shizuoka

  • National Cancer Center Hospital

    Tokyo

  • The Cancer Institute Hospital of Japanese Foundation for Cancer Research

    Tokyo

Other trials in Japan

Taiwan5 sites

  • Chang Gung Medical Foundation Chiayi Chang Gung Memorial Hospital

    Chiayi City

  • Chung Shan Medical University Hospital

    Taichung

  • Taichung Veterans General Hospital

    Taichung

  • National Taiwan University Hospital

    Taipei, 10002

  • Taipei Medical University Hospital

    Taipei

Other trials in Taiwan

Netherlands2 sites

  • The Netherlands Cancer Institute (NKI)

    Amsterdam, 1066 CX

  • Leiden University Medical Center

    Leiden, 2333 ZA

Other trials in Netherlands

Singapore2 sites

  • Singapore Clinical Research Institute

    Singapore, 138669

  • National Cancer Centre Singapore

    Singapore, 169610

Other trials in Singapore

Hong Kong1 site

  • Hong Kong University - Queen Mary Hospital

    Hong Kong

Other trials in Hong Kong

About this study

Official title: A Phase 1/2, Open-Label, Multi-Center Trial to Assess Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of CLN-081 in Patients With Locally-Advanced or Metastatic Non-Small Cell Lung Cancer Harboring EGFR Exon 20 Insertion Mutations Who Have Previously Received Platinum-Based Systemic Chemotherapy

CLN-081-001 is a Phase 1/2, open label, multi-center study of CLN-081 in patients with non-small cell lung cancer (NSCLC) harboring EGFR (epidermal growth factor receptor) exon 20 insertion mutations, to characterize the safety, determine the recommended Phase 2 dose (RP2D), and evaluate efficacy.

Read the detailed description

This is a Phase 1/2, open-label, multicenter, first-in-human trial to evaluate the safety and tolerability, PK, PD, and 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 multiple parts: Phase 1 Dose Escalation, Phase 2a Dose Expansion, Module A, Module B, and Module C.

The objectives of the dose escalation and dose expansion parts are to determine the safety, tolerability, recommended Phase 2 dose (RP2D), and preliminary anti-tumor activity of orally administered CLN-081 monotherapy.

The objective of Module A is to preliminarily assess the effect of food on the PK profile of CLN-081.

The objective of Module B is to further characterize the safety and efficacy of CLN-081 monotherapy in patients with EGFR exon 20 insertion mutation NSCLC who have received prior systemic anti-cancer treatment for locally advanced or metastatic disease.

The objective of Module C is to explore the safety, tolerability, and efficacy of CLN-081 monotherapy in patients with EGFR exon 20 insertion mutation NSCLC who have received prior treatment with an agent approved for EGFR exon 20 insertion mutant NSCLC

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

Being tested
CLN-081
Keywords
NSCLC, EGFR, Exon 20 insertions, CLN-081, TAS6417, zipalertinib
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

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

  • CLN-081Drug

    Also called TAS6417; zipalertinib

    CLN-081 tablets

Study groups in NCT04036682
Study groupRoleWhat they receive
Phase 1 Dose Escalation (Accelerated Titration)ExperimentalCLN-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.
Receives: Drug: CLN-081
Phase 1 Dose Escalation (Rolling Six)ExperimentalCLN-081 BID in Rolling Six dose escalation cohorts enrolling NSCLC patients with EGFR exon 20 insertion mutations.
Receives: Drug: CLN-081
Phase 2a Dose Expansion(s)ExperimentalCLN-081 BID in expansion cohorts that may be opened at doses that meet pre-specified efficacy and safety criteria.
Receives: Drug: CLN-081
Module A Food AffectExperimentalSingle-dose CLN-081 150 mg with and without high fat food intake.
Receives: Drug: CLN-081
Module BExperimentalCLN-081 BID in NSCLC patients with EGFR exon 20 insertion mutations that have received prior systemic therapy for locally advanced or metastatic disease.
Receives: Drug: CLN-081
Module CExperimentalCLN-081 BID to patients with EGFR exon 20 insertion mutant NSCLC after prior therapy with an agent approved for the treatment of ex20ins mutant NSCLC.
Receives: Drug: CLN-081

What is being measured

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

  1. All Cohorts: The rate and severity of treatment emergent AEs.

    Measured: 24 months

  2. All Cohorts: The rate and severity of DLTs.

    Measured: 24 months

  3. Phase 2 Dose Expansion Cohorts: Overall response rate (ORR)

    Measured: 24 months

  4. Module A: Pharmacokinetic (PK) parameter

    Maximum Plasma Concentration [Cmax]

    Measured: 24 months

  5. Module A: Pharmacokinetic (PK) parameter

    Area Under Curve [AUC]

    Measured: 24 months

  6. Module B and C: Confirmed overall response rate (ORR) and duration of response (DOR) by independent review committee (IRC)

    Measured: 24 months

Secondary outcomes (9)

  1. Phase 1 Dose Escalation and Expansion, Phase 2a Dose Expansion, and Module B and C Cohorts: ORR by Investigator assessment

    Measured: 24 months

  2. Phase 1 Dose Escalation and Dose Expansion, Phase 2a Dose Expansion, and Module B and C Cohorts: DOR (duration of response).

    Measured: 24 months

  3. Phase 1 Dose Escalation and Dose Expansion, Phase 2a Dose Expansion, and Module B and C Cohorts: DCR (disease control rate)

    Measured: 24 months

  4. Phase 1 Dose Escalation and Dose Expansion, Phase 2a Dose Expansion, and Module B and C Cohorts: PFS (progression free survival)

    Measured: 24 months

  5. Phase 1 Dose Escalation and Dose Expansion, Phase 2a Dose Expansion, and Module B and C Cohorts: OS (overall survival)

    Measured: 24 months

  6. All Cohorts: Assessment of maximum concentration (Cmax)

    Measured: 24 months

  7. All Cohorts: Assessment of area under curve (AUC)

    Measured: 24 months

  8. All Cohorts: Assessment of time to maximum concentration (tmax)

    Measured: 24 months

  9. All Cohorts: Assessment of terminal half-life (t1/2)

    Measured: 24 months

Timeline

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

  1. First posted30 Jul 2019
  2. Study start31 Oct 2019
  3. Primary completion13 Oct 2025
  4. Study completion31 Mar 2028 (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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
284 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04036682
Sponsor's protocol ID
CLN-081-001
Acronym
REZILIENT1
Status last verified
Jun 2026
First submitted
23 Jul 2019
Last updated
17 Jun 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Piotrowska Z, Passaro A, Nguyen D, Ruiter G, Soo RA, Ho-Fun Lee V, Velcheti V, Tan DS, Lee SH, Kim SH, Wrangle J, Yang JC, Daga H, Juan Vidal OJ, Spira AI, Fernandez-Hinojal G, Kim SW, Umemura S, Provencio Pulla M, Keeton EK, Yang ZS, Li S, Xu ZC, Jones JA, Yu HA; REZILIENT1 Investigators. Zipalertinib in Patients With Epidermal Growth Factor Receptor Exon 20 Insertion-Positive Non-Small Cell Lung Cancer Previously Treated With Platinum-Based Chemotherapy With or Without Amivantamab. J Clin Oncol. 2025 Jul 20;43(21):2387-2397. doi: 10.1200/JCO-25-00763. Epub 2025 Jun 1.

    PubMed 40450572

  • Piotrowska Z, Tan DS, Smit EF, Spira AI, Soo RA, Nguyen D, Lee VH, Yang JC, Velcheti V, Wrangle JM, Socinski MA, Koczywas M, Janik JE, Jones J, Yu HA. Safety, Tolerability, and Antitumor Activity of Zipalertinib Among Patients With Non-Small-Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Exon 20 Insertions. J Clin Oncol. 2023 Sep 10;41(26):4218-4225. doi: 10.1200/JCO.23.00152. Epub 2023 Jun 29.

    PubMed 37384848

  • Ye L, Chen X, Zhou F. EGFR-mutant NSCLC: emerging novel drugs. Curr Opin Oncol. 2021 Jan;33(1):87-94. doi: 10.1097/CCO.0000000000000701.

    PubMed 33122578

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CLN-081 in people with Non Small Cell Lung Cancer and EGFR Exon 20 Mutation, run by Cullinan Therapeutics Inc. at 64 sites in 9 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 21 inclusion and 36 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 17 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 64 sites in United States, Spain, South Korea, Italy, Japan and 4 more countries. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

All Cohorts: The rate and severity of treatment emergent AEs. (time frame: 24 months). The study lists 6 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 NCT04036682, which also lists 3 linked publications.

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 17 Jun 2026.

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