A Phase 1/2 Trial of CLN-081 in Patients With Non-Small Cell Lung Cancer
- Conditions
- Non Small Cell Lung CancerEGFR Exon 20 Mutation
- Interventions
- 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).
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 284
Not provided
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)
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
ðŸ‡ðŸ‡°Hong Kong, Hong Kong