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

NCT04036682 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: CLN-081-001
• Study Type: interventional
• Target: 284
• Locations: 9 countries
• Sites: 64

Brief 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.

Conditions

Non Small Cell Lung Cancer; EGFR Exon 20 Mutation

Keywords

NSCLC; EGFR; Exon 20 insertions; CLN-081; TAS6417; zipalertinib

Outcome Measures

Primary Outcomes (6)

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

  24 months

• All Cohorts: The rate and severity of DLTs.

  24 months

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

  24 months

• Module A: Pharmacokinetic (PK) parameter

  Maximum Plasma Concentration \[Cmax\]

  24 months

• Module A: Pharmacokinetic (PK) parameter

  Area Under Curve \[AUC\]

  24 months

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

  24 months

Secondary Outcomes (9)

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

  24 months

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

  24 months

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

  24 months

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

  24 months

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

  24 months

Study Arms (6)

Phase 1 Dose Escalation (Accelerated Titration)

EXPERIMENTAL

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

Phase 1 Dose Escalation (Rolling Six)

EXPERIMENTAL

CLN-081 BID in Rolling Six dose escalation cohorts enrolling NSCLC patients with EGFR exon 20 insertion mutations.

Drug: CLN-081

Phase 2a Dose Expansion(s)

EXPERIMENTAL

CLN-081 BID in expansion cohorts that may be opened at doses that meet pre-specified efficacy and safety criteria.

Drug: CLN-081

Module A Food Affect

EXPERIMENTAL

Single-dose CLN-081 150 mg with and without high fat food intake.

Drug: CLN-081

Module B

EXPERIMENTAL

CLN-081 BID in NSCLC patients with EGFR exon 20 insertion mutations that have received prior systemic therapy for locally advanced or metastatic disease.

Drug: CLN-081

Module C

EXPERIMENTAL

CLN-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.

Drug: CLN-081

Interventions

CLN-081 DRUG

CLN-081 tablets

Also known as: TAS6417; zipalertinib

Module A Food Affect; Module B; Module C; Phase 1 Dose Escalation (Accelerated Titration); Phase 1 Dose Escalation (Rolling Six); Phase 2a Dose Expansion(s)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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:

Sponsors & Collaborators

• Cullinan Therapeutics Inc.: lead

Study Sites (64)

Pacific Cancer Medical Center, Inc

Anaheim, California, 92801, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

City of Hope at Irvine Lennar

Irvine, California, 92618, United States

Location

Pacific Shores Medical Group

Long Beach, California, 90813, United States

Location

AdventHealth

Orlando, Florida, 32804, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Michigan Health System - University Hospital

Ann Arbor, Michigan, 48109, United States

Location

Summit Medical Group PA

Florham Park, New Jersey, 07932, United States

Location

Perlmutter Cancer Center at NYU Langone Hospital - Long Island

Mineola, New York, 11501, United States

Location

New York University Langone Health

New York, New York, 10016, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Gabrail Cancer Center Research

Canton, Ohio, 44701, United States

Location

Providence Cancer Center

Portland, Oregon, 97213, United States

Location

Providence Oncology & Hematology Care Clinic-Westside

Portland, Oregon, 97225, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Hong Kong University - Queen Mary Hospital

Hong Kong, Hong Kong

Location

Azienda Ospedaliero Universitaria Careggi

Careggi, Italy

Location

Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I

Marche, Italy

Location

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

Meldola, Italy

Location

IRCCS-Istituto Europeo di Oncologia

Milan, Italy

Location

Azienda Ospedaliero Universitaria Modena

Modena, Italy

Location

San Gerardo Hospital

Monza, Italy

Location

Ospedale Santa Maria delle Croci

Ravenna, Italy

Location

National Cancer Center Hospital East

Chiba, Japan

Location

Niigata Cancer Center

Niigata, Japan

Location

Osaka City General Hospital

Osaka, Japan

Location

Osaka International Cancer Institute

Osaka, Japan

Location

Shizuoka Cancer Center

Shizuoka, Japan

Location

National Cancer Center Hospital

Tokyo, Japan

Location

The Cancer Institute Hospital of Japanese Foundation for Cancer Research

Tokyo, Japan

Location

The Netherlands Cancer Institute (NKI)

Amsterdam, 1066 CX, Netherlands

Location

Leiden University Medical Center

Leiden, 2333 ZA, Netherlands

Location

Singapore Clinical Research Institute

Singapore, 138669, Singapore

Location

National Cancer Centre Singapore

Singapore, 169610, Singapore

Location

National Cancer Center

Goyang-si, South Korea

Location

Seoul National University Bundang Hospital (SNUBH)

Gyeonggi-do, South Korea

Location

Gachon University Gil Medical Center

Incheon, South Korea

Location

Inha University Hospital

Incheon, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Asan Medical Center (AMC)

Soeul, South Korea

Location

Korea University Guro Hospital

Soeul, South Korea

Location

Ajou University Hospital

Suwon, South Korea

Location

The Catholic University Of Korea St. Vincent's Hospital

Suwon, South Korea

Location

University Hospital A Coruna

A Coruña, Spain

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, Spain

Location

Hospital Parc Tauli

Barcelona, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, Spain

Location

Institut Catala d'Oncologia l'Hospitalet

Barcelona, Spain

Location

START Barcelona

Barcelona, Spain

Location

Complejo Hospitalario Universitario Insular Materno Infantil

Las Palmas, Spain

Location

Hospital General Universitario Gregorio Maranon (HGUGM)

Madrid, Spain

Location

Hospital Universitario Puerta de Hierro de Majadahonda

Madrid, Spain

Location

University Hospital Quironsalud Madrid

Madrid, Spain

Location

Hospital Regional Universitario de Malaga

Málaga, Spain

Location

Clinica Universidad de Navarra

Pamplona, Spain

Location

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

Valencia, Spain

Location

Chang Gung Medical Foundation Chiayi Chang Gung Memorial Hospital

Chiayi City, Taiwan

Location

Chung Shan Medical University Hospital

Taichung, Taiwan

Location

Taichung Veterans General Hospital

Taichung, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Taipei Medical University Hospital

Taipei, Taiwan

Location

Related Publications (3)

• 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.

  PMID: 40450572 DERIVED

• 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.

  PMID: 37384848 DERIVED

• 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.

  PMID: 33122578 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

zipalertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Zosia Piotrowska, MD

  Massachusetts General Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2019
• First Posted: July 30, 2019
• Study Start: October 31, 2019
• Primary Completion: January 31, 2026
• Study Completion: March 31, 2026
• Last Updated: March 13, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (18); JP (7); ES (13); NL (2); SG (2); TW (5); KR (9); HK (1); IT (7)