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

Phase 1

Recruiting

• Conditions: Non Small Cell Lung Cancer; EGFR Exon 20 Mutation
• Interventions: Drug: CLN-081

• Registration Number: NCT04036682
• Lead Sponsor: Cullinan Therapeutics Inc.

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.

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).

Study Timeline

• Study First Submitted: 2019-07-23
• Study First Submitted QC: 2019-07-25
• Study First Posted: 2019-07-30
• Study Start: 2019-10-31
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-24
• Last Update Posted: 2024-04-26
• Primary Completion: 2024-12-31
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 284

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Module C	CLN-081	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.
Phase 1 Dose Escalation (Accelerated Titration)	CLN-081	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.
Phase 1 Dose Escalation (Rolling Six)	CLN-081	CLN-081 BID in Rolling Six dose escalation cohorts enrolling NSCLC patients with EGFR exon 20 insertion mutations.
Module A Food Affect	CLN-081	Single-dose CLN-081 150 mg with and without high fat food intake.
Phase 2a Dose Expansion(s)	CLN-081	CLN-081 BID in expansion cohorts that may be opened at doses that meet pre-specified efficacy and safety criteria.
Module B	CLN-081	CLN-081 BID in NSCLC patients with EGFR exon 20 insertion mutations that have received prior systemic therapy for locally advanced or metastatic disease.

Primary Outcome Measures

Name	Time	Method
All Cohorts: The rate and severity of DLTs.	24 months
Phase 2 Dose Expansion Cohorts: Overall response rate (ORR)	24 months
Module B and C: Confirmed overall response rate (ORR) and duration of response (DOR) by independent review committee (IRC)	24 months
All Cohorts: The rate and severity of treatment emergent AEs.	24 months
Module A: Pharmacokinetic (PK) parameter	24 months	Area Under Curve \[AUC\]

Secondary Outcome Measures

Name	Time	Method
All Cohorts: Assessment of maximum concentration (Cmax)	24 months
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
All Cohorts: Assessment of terminal half-life (t1/2)	24 months
Phase 1 Dose Escalation and Dose Expansion, Phase 2a Dose Expansion, and Module B and C Cohorts: OS (overall survival)	24 months
All Cohorts: Assessment of time to maximum concentration (tmax)	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
All Cohorts: Assessment of area under curve (AUC)	24 months

Trial Locations

Locations (64)

Asan Medical Center (AMC); 🇰🇷 Soeul, Korea, Republic of

Pacific Cancer Medical Center, Inc; 🇺🇸 Anaheim, California, United States

City of Hope Comprehensive Cancer Center; 🇺🇸 Duarte, California, United States

City of Hope at Irvine Lennar; 🇺🇸 Irvine, California, United States

Pacific Shores Medical Group; 🇺🇸 Long Beach, California, United States

AdventHealth; 🇺🇸 Orlando, Florida, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

University of Michigan Health System - University Hospital; 🇺🇸 Ann Arbor, Michigan, United States

Summit Medical Group PA; 🇺🇸 Florham Park, New Jersey, United States

Perlmutter Cancer Center at NYU Langone Hospital - Long Island; 🇺🇸 Mineola, New York, United States

New York University Langone Health; 🇺🇸 New York, New York, United States

Columbia University Irving Medical Center; 🇺🇸 New York, New York, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Gabrail Cancer Center Research; 🇺🇸 Canton, Ohio, United States

Providence Cancer Center; 🇺🇸 Portland, Oregon, United States

Providence Oncology & Hematology Care Clinic-Westside; 🇺🇸 Portland, Oregon, United States

UPMC Hillman Cancer Center; 🇺🇸 Pittsburg, Pennsylvania, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

Virginia Cancer Specialists; 🇺🇸 Fairfax, Virginia, United States

Azienda Ospedaliero Universitaria Careggi; 🇮🇹 Careggi, Italy

Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I; 🇮🇹 Marche, Italy

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS; 🇮🇹 Meldola, Italy

IRCCS-Istituto Europeo di Oncologia; 🇮🇹 Milano, Italy

Azienda Ospedaliero Universitaria Modena; 🇮🇹 Modena, Italy

San Gerardo Hospital; 🇮🇹 Monza, Italy

Ospedale Santa Maria delle Croci; 🇮🇹 Ravenna, Italy

National Cancer Center Hospital East; 🇯🇵 Chiba, Japan

Niigata Cancer Center; 🇯🇵 Niigata, Japan

Osaka City General Hospital; 🇯🇵 Osaka, Japan

Osaka International Cancer Institute; 🇯🇵 Osaka, Japan

Shizuoka Cancer Center; 🇯🇵 Shizuoka, Japan

National Cancer Center Hospital; 🇯🇵 Tokyo, Japan

The Cancer Institute Hospital of Japanese Foundation for Cancer Research; 🇯🇵 Tokyo, Japan

National Cancer Center; 🇰🇷 Goyang-si, Korea, Republic of

Seoul National University Bundang Hospital (SNUBH); 🇰🇷 Gyeonggi-do, Korea, Republic of

Gachon University Gil Medical Center; 🇰🇷 Incheon, Korea, Republic of

Inha University Hospital; 🇰🇷 Incheon, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

Korea University Guro Hospital; 🇰🇷 Soeul, Korea, Republic of

Ajou University Hospital; 🇰🇷 Suwon-si, Korea, Republic of

The Catholic University Of Korea St. Vincent's Hospital; 🇰🇷 Suwon-si, Korea, Republic of

The Netherlands Cancer Institute (NKI); 🇳🇱 Amsterdam, Netherlands

Leiden University Medical Center; 🇳🇱 Leiden, Netherlands

Singapore Clinical Research Institute; 🇸🇬 Singapore, Singapore

National Cancer Centre Singapore; 🇸🇬 Singapore, Singapore

University Hospital A Coruna; 🇪🇸 A Coruña, Spain

Hospital Clinic i Provincial de Barcelona; 🇪🇸 Barcelona, Spain

Hospital Parc Tauli; 🇪🇸 Barcelona, Spain

Hospital Universitario Vall d'Hebron; 🇪🇸 Barcelona, Spain

Institut Catala d'Oncologia l'Hospitalet; 🇪🇸 Barcelona, Spain

START Barcelona; 🇪🇸 Barcelona, Spain

Complejo Hospitalario Universitario Insular Materno Infantil; 🇪🇸 Las Palmas, Spain

Hospital General Universitario Gregorio Maranon (HGUGM); 🇪🇸 Madrid, Spain

Hospital Universitario Puerta de Hierro de Majadahonda; 🇪🇸 Madrid, Spain

University Hospital Quironsalud Madrid; 🇪🇸 Madrid, Spain

Hospital Regional Universitario de Malaga; 🇪🇸 Málaga, Spain

Clinica Universidad de Navarra; 🇪🇸 Pamplona, Spain

Universitat de Valencia - Hospital Universitari i Politecnic La Fe de Valencia (Hospital La Fe Bulevar Sur); 🇪🇸 Valencia, Spain

Chang Gung Medical Foundation Chiayi Chang Gung Memorial Hospital; 🇨🇳 Chiayi City, Taiwan

Chung Shan Medical University Hospital; 🇨🇳 Taichung, Taiwan

Taichung Veterans General Hospital; 🇨🇳 Taichung, Taiwan

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

Taipei Medical University Hospital; 🇨🇳 Taipei, Taiwan

Hong Kong University - Queen Mary Hospital; 🇭🇰 Hong Kong, Hong Kong