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Lung Diseases

Respiratory Tract Diseases

Patients receive poziotinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Poziotinib

Yasir Y Elamin

This phase II trial studies how well poziotinib works in treating patients with non-small lung cancer with an EGFR or HER2 exon 20 mutation that is stage IV or has come back (recurrent). Poziotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth..

PRIMARY OBJECTIVES:

I. To assess the objective response rate (ORR) to poziotinib according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria in non-small cell lung cancer (NSCLC) with EGFR exon 20 mutations.

II. Assess the objective response rate (ORR) to poziotinib according to RECIST 1.1 criteria in NSCLC with HER2 (ErBB2) exon 20 mutations.

III. Assess the objective response rate (ORR) to poziotinib according to RECIST 1.1 criteria in advanced solid tumors with EGFR exon 20 or HER2 exon 20 mutations.

IV. Assess the objective response rate (ORR) to poziotinib according to RECIST 1.1 criteria in advanced solid tumors with HER2 exon 19 mutations ORR will be calculated as the percent of patients whose best confirmed response is complete response (CR, defined as disappearance of all target lesions) or partial response (PR, defined as at least a 30% decrease in the sum of longest diameter \[LD\] of target lesions, taking as reference the baseline sum LD).

SECONDARY OBJECTIVES:

I. Disease control rate (complete response + partial response + stable response) of poziotinb in cohort 1 and 2, analyzed independently.

II. Progression free survival of poziotinb in cohort 1 and 2, analyzed independently.

III. Overall survival of poziotinb in cohort 1 and 2, analyzed independently. IV. Duration of response of poziotinb in cohort 1 and 2, analyzed independently.

V. Safety and toxicity.

EXPLORATORY OBJECTIVES:

I. To assess molecular markers associated with resistance and response to poziotinib, including secondary mutations.

OUTLINE:

Patients receive poziotinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 6 months thereafter.

Poziotinib in EGFR Exon 20 Mutant Advanced NSCLC

A Phase II Study of Poziotinib in EGFR or HER2 Mutant Advanced Solid Tumors

According to Response Evaluation Criteria in Solid Tumors 1.1 criteria.

Will be estimated along with 95% confidence intervals.

Will be estimated using the Kaplan-Meier method and the comparison between or among patient's characteristic groups will be evaluated by log-rank test. The Cox regression model may be applied to assess the effect of covariates of interest on progression free survival.

Will be estimated using the Kaplan-Meier method and the comparison between or among patient's characteristic groups will be evaluated by log-rank test. The Cox regression model may be applied to assess the effect of covariates of interest on overall survival.

Assessed by Common Terminology Criteria for Adverse Events version 4.03. Toxicity data will be summarized by frequency tables.

National Cancer Institute (NCI)

Spectrum Pharmaceuticals, Inc

M.D. Anderson Cancer Center

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.

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

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

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

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

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.

CLN-081

Shengting Li, MD, PhD

Jackie Bronicki

Elizabeth Brown

Veena Charu

Valeria Estala

Danny Nguyen, MD

Juan Miranda

Danny Nguyen

Jesse Ruiz

Jeffrey Kettler

Mark Socinski, MD

Olivia Deloney

Zosia Piotrowska, MD

Dhaman Bansal

Gregory Kalemkerian

Michelle Mackenzie

Sarada Gurubhagavatula

Tomislav Vucetic

Vamsidhar Velcheti, MD

Moury Minhaz

Catherine Shu, MD

Khadeja Moses

Helena Yu, MD

Amanda Rich

Nashat Y Gabrail, MD

Lynn Freitas

Rachel E Sanborn, MD

Rachel Sanborn

Keagan Buttigieg

Timothy Burns, MD, PhD

Jessica Shealor

John Wrangle, MD

Karina Castillo Grady

Alex Spira, MD, PhD

Mike Law

Victor Ho-Fun Lee, MBBS

Francesca Zepponi

Lorenzo Antonuzzo, MD, PhD

Michela Burattini

Rossana Berardi, MD

Martina Magnani

Angelo Delmonte, MD

Daniela Brambilla

Antonio Passaro, MD, PhD

Elisa Pettorelli

Michela Maur, MD

Alessandra Carbone

Diego Cortinovis, MD

Michela Spreadfico

Chiara Bennati, MD

Yuka Sakamoto

Shigeki Umemura, MD, PhD

Yoshihiro Kusama

Hiroshi Tanaka, MD, PhD

Ai Kitamoto

Haurko Daga

Tatsuya Takeuchi

Nishino Kazumi, MD, PhD

Tomomi Endo

Haruyasu Murakami, MD, PhD

Hiroko Kawaguchi

Yuichiro Ohe, MD, PhD

Yurina Nishizawa

Satoru Kitazono, MD, PhD

KyoungSuk Kwon

Ji-Youn Han, MD, PhD

YeonSeon Jeon

Se Hyun Kim, MD

SoHee Choi

Hee Kyung Ahn, MD

Jin MinHee

Jun Hyeok Lim, MD

Jungkyo Kim

Se-Hoon Lee, MD, PhD

Gyeong Min

Sang-we Kim

Ye Song Kim

Sung-Yong Lee

Ji Eun Seo

Hyun Woo Lee

EunYeong Lee

Byoung Yong Shim

Marianne Mahn

Gerrina Ruiter

Kristen Wilkens-Bak

Egbert Smit, MD, PhD

Sheryl St Chong

Ross Soo, MBBS

Vivian Oo Shiyun Fequira

Daniel Shao Weng Tan, MBBS, PhD

Graciela Vanesa Alvarez

Maria Rosario Garcia Campelo, MD

Anna Clua

Laura Mezquita Perez, MD, PhD

Jose Garcia Ruiz

Julia Giner Joaquin, MD

Ana Matres Rojo

Enriqueta Felip Font, MD, PhD

Antonio Davila

Ernesto Samuel Nadal Alforia, MD, PhD

Monica Alemany

Tatiana Hernandez, MD

Elia Garcia Ojeda

Delvys Rodriguez Abreu, MD, PhD

Cristina Rodriguez Villar

Antonio Calles Blanco, MD

Carmen Garcia Delgado

Mariano Provencio Pulla, MD, PhD

Uxue Nunez

Valentina Boni, MD

Alicia Medina Ramos

Manual Cobo Dols, MD, PhD

Sara Diaz

Eduardo Castanon Alvarez, MD

Carmina Rodrigo

Oscar Juan Vidal, MD, PhD

Chien-Ting Hung

Yu-Ching Lin, MD, PhD

Lung-Ying Huang

Gee-Chen Chang, MD, PhD

Wen-Ling Chen

Tsung-Ying Yang, MD, PhD

Jin-Rong Chen

James Chin-Hsin Yang, MD

Chen-chuan Chu

Chao-Hua Chiu, MD

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.

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).

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

A Phase 1/2, Open-Label, Multi-Center Trial to Assess Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of CLN-081 in Patients With Locally-Advanced or Metastatic Non-Small Cell Lung Cancer Harboring EGFR Exon 20 Insertion Mutations Who Have Previously Received Platinum-Based Systemic Chemotherapy

Cullinan Therapeutics Inc.

Nervous System Diseases

Adenocarcinoma

Neoplasm Metastasis

Neoplasms by Histologic Type

Brain Neoplasms

Neoplasms, Glandular and Epithelial

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Bronchial Diseases

Antineoplastic Agents

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Micronutrients

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Amino Acids

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Carboplatin

Pemetrexed

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Protein Kinase Inhibitors

Mobocertinib

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

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Tyrosine

Folinic Acid

Folate

Vitamin B9

BLU-451 monotherapy with dose escalation in participants with metastatic cancer with EGFR Ex20ins or other selected EGFR mutations that have progressed after prior systemic therapies.

BLU-451 with dose escalation in combination with carboplatin and pemetrexed in participants with metastatic NSCLC with common EGFR mutations. This arm will enroll participants only in the United States.

EGFR Ex20ins participants who have previously received platinum-based chemotherapy and either amivantamab or mobocertinib will receive BLU-451.

EGFR Ex20ins participants who have previously received platinum-based chemotherapy but have not received a prior EGFR Ex20ins-targeted agent will receive BLU-451.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Poziotinib in EGFR Exon 20 Mutant Advanced NSCLC	NCT03066206	EGFR Exon 20 Mu... ERBB2 Gene Muta... Recurrent Lung ... Stage IV Non-Sm...	Poziotinib	18 Years -	M.D. Anderson Cancer Center
A Phase 1/2 Trial of CLN-081 in Patients With Non-Small Cell Lung Cancer	NCT04036682	Non Small Cell ... EGFR Exon 20 Mu...	CLN-081	18 Years -	Cullinan Therapeutics Inc.
Poziotinib in EGFR Exon 20 Mutant Advanced NSCLC	NCT03066206	EGFR Exon 20 Mu... ERBB2 Gene Muta... Recurrent Lung ... Stage IV Non-Sm...	Poziotinib	18 Years -	M.D. Anderson Cancer Center
(Concerto) Study of BLU-451 in Advanced Cancers With EGFR Exon 20 Insertion Mutations	NCT05241873	Lung Neoplasm M... Carcinoma, Non-... Respiratory Tra... Neoplasms Neoplasms by Si... Lung Diseases Respiratory Tra... Carcinoma, Bron... Bronchial Neopl... Adenocarcinoma Carcinoma Neoplasms by Hi... EGFR Exon 20 Mu... EGFR Exon 20 In... EGFR Activating... Antineoplastic ... Metastatic Lung... Brain Metastase... EGFR-mutated NS... EGFR Atypical M...	BLU-451 Carboplatin Pemetrexed	18 Years -	Blueprint Medicines Corporation

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