ELVN-002 in HER2 Mutant Non-Small Cell Lung Cancer

HER2-positive Metastatic Breast Cancer Clinical Trial

— HER2  

Official title:

A Phase 1a/1b Study of ELVN-002 for the Treatment of Patients With HER2 Mutant Non-Small Cell Lung Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05650879
• Other study ID #: ELVN-002-001
• Status: Recruiting
• Phase: Phase 1
• Start date: March 20, 2023
• Est. completion date: July 2026

Study information

• Verified date: March 2024
• Source: Enliven Therapeutics
• Contact: Helen L Collins, MD
• Phone: 707 799-3272
• Email: helen.collins[@]enliventherapeutics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to test ELVN-002 in people with cancers that have an abnormal HER2 gene. The main question the trial aims to answer is if ELVN-002 is safe and tolerable at different doses. A second main question is to evaluate the concentration of ELVN-002 in the blood at different doses and to see how this correlates with safety and see how the concentration of drug changes over time. The third main question is to see if ELVN-002 works to shrink cancers that have HER2 genetic abnormalities, particularly non-small cell lung cancer.

Description:

There are 4 parts to the trial. Part 1 is a dose escalation with ELVN-002 monotherapy for people with advanced stage solid tumors that have a HER2 mutation, amplification or high HER2 over-expression. Part 2 is an ELVN-002 monotherapy dose exploration where additional people may be enrolled at dose levels that have cleared the dose escalation in Part 1 to further evaluate the safety, tolerability, pharmacokinetics and clinical activity. Part 3 is a dose expansion of ELVN-002 monotherapy which will enroll up to 40 patients people with advanced stage HER2 mutant non-small cell lung cancer. Patients in Part 3 will be randomized 1:1 to receive one of two dose levels. Part 4 is a combination dose escalation where, based on the results of Part 1 and 2, a combination of ELVN-002 and either fam-trastuzumab deruxtecan-nxki (in HER2 mutant non-small cell lung cancer) or trastuzumab emtansine (in HER2 positive breast cancer) will be evaluated for safety and tolerability.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 178
• Est. completion date: July 2026
• Est. primary completion date: July 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Phase 1a Monotherapy Dose Escalation and Exploration:

• Pathologically documented advanced stage solid tumor
• Progressed following all standard treatment or not appropriate for standard treatment
• HER2 mutation, HER2 amplification or HER2 positive based on local testing Phase 1b Monotherapy
• Pathologically documented unresectable and/or metastatic non-squamous NSCLC
• HER2 mutation identified by tissue (fresh or archival) or ctDNA. Local testing for up to 20 patients the remainder centrally confirmed.
• Measurable disease
• No known epidermal growth factor receptor (EGFR), ROS1, anaplastic lymphoma kinase (ALK), or BRAF V600E mutation
• Progressed after receiving at least 1 prior systemic therapy including a platinum-based chemotherapy with or without immunotherapy, or not appropriate for standard treatment.
• No prior HER2 tyrosine kinase inhibitor. Prior HER2 directed antibodies or anti-body drug conjugates are allowed
• No limit on prior number of therapies Phase 1a Combination with T-DXd
• Pathologically documented advanced stage NSCLC
• Progressed after receiving at least 1 prior systemic therapy.
• HER2 mutation based on local/historical testing of tissue or circulating tumor DNA
• No known EGFR, ROS1, ALK, or BRAF V600E mutation
• No prior T-DXd
• No clinically severe pulmonary compromise
• No limit on prior number of therapies Phase 1a Combination Breast Cancer
• Documented HER2 positive (Immunohistochemical [IHC] 3+ or IHC2+/in situ hybridization (ISH+) breast cancer
• Must have previously received trastuzumab, a taxane, and T-DXd (if available and appropriate) in the metastatic setting.
• No limit on prior number of therapies
• No prior T-DM1 All Phases
• Eastern Cooperative Oncology Group performance status of 0-1
• Left ventricular ejection fraction = 50%
• Platelet count = 100 x 109/L
• Hemoglobin = 8.5 g/dL
• Absolute neutrophil count =1.0 x 109/L
• Total bilirubin < 1.5 times upper limit of normal range (ULN), except for patients with Gilbert's syndrome
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) < 3 times ULN. In the setting of liver metastases < 5 times ULN.
• Creatinine clearance = 60 mL/minute

Exclusion Criteria All Phases:

• Severe cardiac arrhythmias, requiring treatment, symptomatic congestive heart failure, myocardial infarction within 28 days prior to first dose, or unstable angina.
• Another active malignancy within 2 years except basal cell skin cancer and carcinoma in situ treated curatively
• Active or chronic liver disease
• Active infection requiring systemic therapy within 14 days before the first dose
• Brain lesion requiring immediate local therapy
• Leptomeningeal disease
• Uncontrolled seizures
• Corrected QT interval (QTc) of >470 milliseconds (ms) females or >450 ms for males by Fridericia (QTcF)

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• HER2 Gene Mutation
• HER2-positive Metastatic Breast Cancer
• Lung Neoplasms

Intervention

Drug:
• ELVN-002
capsule
• Fam-Trastuzumab Deruxtecan-Nxki
intravenous
• Trastuzumab emtansine
intravenous

Locations

Country	Name	City	State
Australia	Blacktown Hospital	Darlinghurst
Australia	Linear Clinical Research Limited	Nedlands	Western Australia
Australia	Macquarie University Hospital	Westmead	New South Wales
France	EDOG - Institut Bergonie - PPDS	Bordeaux	Gironde
France	Centre Francois Baclesse	Caen	Calvados
France	Centre Georges François Leclerc	Dijon	Côte-d'Or
France	Centre Léon Berard	Lyon	Cedex 8
France	Hôpital de la Timone Centre d'essais en cancérologie de Marseille (CEPCM-CLIPP)	Marseille	Bouches-du-Rhône
France	Hôpital Pontchaillou	Rennes	Brittany
France	Institut Gustave Roussy (IGR)	Villejuif Cedex
Italy	Azienda Ospedaliero Universitaria delle Marche	Ancona	Marche
Italy	SOC Oncologia Medica e dei Tumori lmmunocorrelati, Centro Di Riferimento Oncologico Di Aviano (CRO) IRCCS	Aviano	Pordenone
Italy	Fondazione del Piemonte per l'Oncologia (IRCCS)	Candiolo	Piemonte
Italy	Fondazione IRCCS San Gerardo dei Tintori	Monza	Lombardia
Italy	Fondazione Policlinico Universitario A. Gemelli	Roma
Italy	Unità Operativa Oncologia medica ed Ematologia	Rozzano
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severence Hospital, Yonsei University	Seoul
Korea, Republic of	The Catholic University of Korea, St. Vincent's Hospital	Suwon	Gyeonggido
Spain	START Barcelona Hospital HM Nou Delfos	Barcelona
Spain	lnstitut Catala d'Oncologia (ICO) L'Hospitalet, Servicio de Oncologia Medica	L'Hospitalet de Llobregat
Spain	Hospital Universitari Arnau de Vilanova	Lleida
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Fundación Jiménez Díaz	Madrid
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital Universitari i Politècnic La Fe	Valencia
Taiwan	Taichung Veterans General Hospital	Taichung City
Taiwan	National Chen Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei City
United States	University of Colorado - Anschutz Medical Campus - PPDS	Aurora	Colorado
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	NEXT/Virginia Cancer Specialists	Fairfax	Virginia
United States	Advent Health Orlando	Orlando	Florida
United States	BRCR Medical Center Inc	Plantation	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Enliven Therapeutics

Countries where clinical trial is conducted

United States,  Australia,  France,  Italy,  Korea, Republic of,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose limiting toxicities in Phase 1a monotherapy		21 days
Primary	Incidence of adverse events in Phase 1a monotherapy		24 months
Primary	incidence of laboratory abnormalities in Phase 1a monotherapy		24 months
Primary	incidence of ECG abnormalities in Phase 1a monotherapy		24 months
Primary	incidence of dose limiting toxicities in Phase 1a combination with fam-trastuzumab deruxtecan (T-DXd)		42 days
Primary	Incidence of adverse events in Phase 1a combination with T-DXd		24 months
Primary	incidence of laboratory abnormalities in Phase 1a combination with T-DXd		24 months
Primary	incidence of ECG abnormalities in Phase 1a combination with T-DXd		24 months
Primary	incidence of dose limiting toxicities in Phase 1a combination with trastuzumab emantasine (T-DM1)		42 days
Primary	Incidence of adverse events in Phase 1a combination with T-DM1		24 months
Primary	incidence of laboratory abnormalities in Phase 1a combination with T-DM1		24 months
Primary	incidence of ECG abnormalities in Phase 1a combination with T-DM1		24 months
Primary	Incidence of adverse events in Phase 1b monotherapy		24 months
Primary	incidence of laboratory abnormalities in Phase 1b monotherapy		24 months
Primary	incidence of ECG abnormalities in Phase 1b monotherapy		24 months
Secondary	Objective Response rate in Phase 1a monotherapy	For patients with measurable disease at baseline, confirmed response per RECIST 1.1	24 months
Secondary	Objective response rate in Phase 1b monotherapy	Confirmed response per RECIST 1.1	24 months
Secondary	Duration of response in Phase 1b monotherapy	The time from the first response to progression or death per RECIST 1.1	24 months
Secondary	Brain metastases response in Phase 1b monotherapy	for patients with measurable brain metastases at baseline, the percent of patients who have a confirmed response per RECIST 1.1	24 months
Secondary	PK parameter of area under the curve of ELVN-002 in Phase 1a monotherapy	the concentration of ELVN-002 measured in the blood over 24 hours at steady state	21 days
Secondary	PK parameter of maximum concentration of ELVN-002 in Phase 1a monotherapy	the maximum concentration of ELVN-002 measured in the blood at any time point at steady state	21 days
Secondary	PK parameter of terminal half life of ELVN-002 in Phase 1a monotherapy	the half life of ELVN-002 calculated from the concentration of ELVN-002 in blood	21 days
Secondary	PK parameter of area under the curve of ELVN-002 in Phase 1b monotherapy	the concentration of ELVN-002 measured in the blood over 24 hours at steady state	21 days
Secondary	PK parameter of maximum concentration of ELVN-002 in Phase 1b monotherapy	the maximum concentration of ELVN-002 measured in the blood at any time point at steady state	21 days
Secondary	PK parameter of terminal half life of ELVN-002 in Phase 1b monotherapy	the half life of ELVN-002 calculated from the concentration of ELVN-002 in blood	21 days