New drug targets rare lung cancer mutation

NCT ID NCT04036682

Disease control Sponsor: Cullinan Therapeutics Inc. Source: ClinicalTrials.gov ↗

First seen Jun 27, 2026 · Last updated Jun 27, 2026

Summary

This study tests an experimental drug called CLN-081 in people with advanced non-small cell lung cancer that has a specific genetic change (EGFR exon 20 insertion). Participants must have already received chemotherapy. The goal is to see if the drug is safe and can shrink tumors.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: CLN-081 (zipalertinib)
What this could lead to: If successful, this could provide a new targeted treatment option for people with a hard-to-treat form of lung cancer.
What could go wrong: This is an early-phase trial, so the drug may not work as hoped or could cause significant side effects. Results may not apply to all patients.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 1/2

Runs two stages together: safety and dose first, then whether the treatment works.

Participants

About 284 people

The number the study aims to enrol. It can still change while the study runs.

Started

Oct 2019

Expected to finish

Mar 2028

An estimate. End dates often move.

Lead sponsor

A company

The lead sponsor is a pharmaceutical, biotech, or medical-device company.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria 1. Histologically or cytologically confirmed locally advanced or metastatic NSCLC (all patients). 2. 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. 3. Prior treatment in the recurrent/metastatic disease setting including: 1. A platinum-based chemotherapy regiment (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. 3. No prior therapy is required for patients enrolled on Module A. 4. Prior therapy with an agent approved by the local regulatory authorities for the treatment of EGFR ex20ins mutant NSCLC (Module C only). 4. Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) (except for patients enrolled on Module A). 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 × 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). 2. Total bilirubin ≤ 1.5 × ULN unless prior history of Gilbert's syndrome. 3. AST and ALT ≤ 2.5 × ULN, or ≤ 5 × ULN if due to liver involvement by tumor. 4. Hemoglobin ≥ 9.0 g/dL in the absence of transfusion ≤ 14 days prior to the first dose of study drug on C1D1. 5. 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). 6. Absolute neutrophil count ≥ 1.5 ×109 cells/L. 9. For Module A patients only: patients must have a negative coronavirus disease 2019 (COVID-19) polymerase chain reaction test prior to enrolment. 10. 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. 11. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria R6, Phase 1 Expansion, Phase 2a, Module A and Module B Patients Only 1. 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 2. Conditions that compromise esophageal or gastrointestinal (GI) function, including esophageal, gastric, pancreatic, hepatobiliary, or small bowel carcinomas, or history of gastric resection. 3. Recurrent diarrhea, nausea, or vomiting. 4. Unable to refrain from or anticipates the use of: 1. 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. 2. 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. 5. Any allergies to the composition of the high fat meal. 6. Patients who use tobacco products. All Patients 7. History of COVID-19-related pneumonitis requiring hospitalization. 8. History of COVID-19 infection within 4 weeks prior to enrolment, or clinically significant pulmonary symptoms related to prior COVID-19 pneumonitis. 9. Treatment with any of the following: 1. 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. 2. Systemic anticancer treatment (excluding EGFR-TKIs as described above) within 14 days prior to the first dose of study drug on C1D1. 3. Immunotherapy ≤ 28 days prior to the first dose of study drug on C1D1. 4. 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. 5. Major surgery (excluding placement of vascular access) ≤ 28 days of the first dose of study drug on C1D1. 10. 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. 11. 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. 12. Prior therapy with CLN-081. 13. Known hypersensitivity to CLN-081 or any drugs similar in structure or class. 14. Past medical history of interstitial lung disease, drug-induced interstitial lung disease, treatment-related pneumonitis, or any evidence of clinically active interstitial lung disease. 15. 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. 16. Resting QTcF \> 470 msec. 17. 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. 18. 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. 19. 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. 20. 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. 21. 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. 22. 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. 23. 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). 24. Active bleeding disorders. 25. The patient is, in the Investigator's opinion, unable or unwilling to comply with the trial procedures.

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Conditions

The condition(s) this trial relates to.

non-small cell lung carcinoma

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

EGFR exon 20 mutation Non-small cell lung cancer

Contacts and locations

Locations

AdventHealth

Orlando, Florida, 32804, United States
Ajou University Hospital

Suwon, South Korea
Asan Medical Center (AMC)

Soeul, South Korea
Azienda Ospedaliero Universitaria Careggi

Careggi, Italy
Azienda Ospedaliero Universitaria Modena

Modena, Italy
Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I

Marche, Italy
Chang Gung Medical Foundation Chiayi Chang Gung Memorial Hospital

Chiayi City, Taiwan
Chung Shan Medical University Hospital

Taichung, Taiwan
City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States
City of Hope at Irvine Lennar

Irvine, California, 92618, United States
Clinica Universidad de Navarra

Pamplona, Spain
Columbia University Irving Medical Center

New York, New York, 10032, United States
Complejo Hospitalario Universitario Insular Materno Infantil

Las Palmas, Spain
Gabrail Cancer Center Research

Canton, Ohio, 44701, United States
Gachon University Gil Medical Center

Incheon, South Korea
Hong Kong University - Queen Mary Hospital

Hong Kong, Hong Kong
Hospital Clinic i Provincial de Barcelona

Barcelona, Spain
Hospital General Universitario Gregorio Maranon (HGUGM)

Madrid, Spain
Hospital Parc Tauli

Barcelona, Spain
Hospital Regional Universitario de Malaga

Málaga, Spain
Hospital Universitario Puerta de Hierro de Majadahonda

Madrid, Spain
Hospital Universitario Vall d'Hebron

Barcelona, Spain
IRCCS-Istituto Europeo di Oncologia

Milan, Italy
Inha University Hospital

Incheon, South Korea
Institut Catala d'Oncologia l'Hospitalet

Barcelona, Spain
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS

Meldola, Italy
Korea University Guro Hospital

Soeul, South Korea
Leiden University Medical Center

Leiden, 2333 ZA, Netherlands
Massachusetts General Hospital

Boston, Massachusetts, 02114, United States
Medical University of South Carolina

Charleston, South Carolina, 29425, United States
Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States
National Cancer Center

Goyang-si, South Korea
National Cancer Center Hospital

Tokyo, Japan
National Cancer Center Hospital East

Chiba, Japan
National Cancer Centre Singapore

Singapore, 169610, Singapore
National Taiwan University Hospital

Taipei, 10002, Taiwan
New York University Langone Health

New York, New York, 10016, United States
Niigata Cancer Center

Niigata, Japan
Osaka City General Hospital

Osaka, Japan
Osaka International Cancer Institute

Osaka, Japan
Ospedale Santa Maria delle Croci

Ravenna, Italy
Pacific Cancer Medical Center, Inc

Anaheim, California, 92801, United States
Pacific Shores Medical Group

Long Beach, California, 90813, United States
Perlmutter Cancer Center at NYU Langone Hospital - Long Island

Mineola, New York, 11501, United States
Providence Cancer Center

Portland, Oregon, 97213, United States
Providence Oncology & Hematology Care Clinic-Westside

Portland, Oregon, 97225, United States
START Barcelona

Barcelona, Spain
Samsung Medical Center

Seoul, South Korea
San Gerardo Hospital

Monza, Italy
Seoul National University Bundang Hospital (SNUBH)

Gyeonggi-do, South Korea
Shizuoka Cancer Center

Shizuoka, Japan
Singapore Clinical Research Institute

Singapore, 138669, Singapore
Summit Medical Group PA

Florham Park, New Jersey, 07932, United States
Taichung Veterans General Hospital

Taichung, Taiwan
Taipei Medical University Hospital

Taipei, Taiwan
The Cancer Institute Hospital of Japanese Foundation for Cancer Research

Tokyo, Japan
The Catholic University Of Korea St. Vincent's Hospital

Suwon, South Korea
The Netherlands Cancer Institute (NKI)

Amsterdam, 1066 CX, Netherlands
UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States
Universitat de Valencia - Hospital Universitari i Politecnic La Fe de Valencia (Hospital La Fe Bulevar Sur)

Valencia, Spain
University Hospital A Coruna

A Coruña, Spain
University Hospital Quironsalud Madrid

Madrid, Spain
University of Michigan Health System - University Hospital

Ann Arbor, Michigan, 48109, United States
Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

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