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

Phase 1

Active, not 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: 2025-03
• Last Update Submitted: 2025-03-11
• Last Update Posted: 2025-03-13
• Primary Completion: 2026-01-31
• Study Completion: 2026-03-31

Recruitment & Eligibility

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

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

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 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.
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.
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)

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

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