ELVN-002 in HER2 Mutant Non-Small Cell Lung Cancer | NCT05650879

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Phase 1a Monotherapy Dose Escalation	Experimental	ELVN-002 will be administered either once or twice daily. Each cohort of patients will receive a higher dose. ELVN-002 is an oral capsule. Duration of treatment will be until disease progression or patient discontinues ELVN-002 for another reason.	Drug: ELVN-002
Phase 1a Monotherapy Dose Exploration	Experimental	ELVN-002 will be administered either once or twice daily. A maximum of 80 patients will enroll in this arm. A maximum of 10 patients may be enrolled at a single dose or tumor type. ELVN-002 is an oral capsule. Duration of treatment will be until disease progression or patient discontinues ELVN-002 for another reason.	Drug: ELVN-002
Phase 1b Monotherapy Dose Expansion	Experimental	ELVN-002 will be administered either once or twice daily. A maximum of 40 patients will enroll in this arm. Patients will be randomized 1:1 to one of two dose levels. ELVN-002 is an oral capsule. Duration of treatment will be until disease progression or patient discontinues ELVN-002 for another reason.	Drug: ELVN-002
Phase 1a Combination Dose Escalation with T-DXd	Experimental	ELVN-002 will be administered either once or twice daily starting on Day 1. ELVN-002 is an oral capsule. Each cohort will receive a higher dose of ELVN-002. All patients in all cohorts will initiate with 5.4mg/kg of intravenous T-DXd once every 3 weeks starting on day 22 of the study. Duration of treatment will be until disease progression or patient discontinues ELVN-002 for another reason.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
ELVN-002	Drug	capsule	Phase 1a Combination Dose Escalation with T-DM1 Phase 1a Combination Dose Escalation with T-DXd Phase 1a Monotherapy Dose Escalation

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Incidence of dose limiting toxicities in Phase 1a monotherapy		21 days
Incidence of adverse events in Phase 1a monotherapy		24 months
incidence of laboratory abnormalities in Phase 1a monotherapy		24 months
incidence of ECG abnormalities in Phase 1a monotherapy		24 months
incidence of dose limiting toxicities in Phase 1a combination with fam-trastuzumab deruxtecan (T-DXd)		42 days
Incidence of adverse events in Phase 1a combination with T-DXd		24 months
incidence of laboratory abnormalities in Phase 1a combination with T-DXd		24 months
incidence of ECG abnormalities in Phase 1a combination with T-DXd		24 months
incidence of dose limiting toxicities in Phase 1a combination with trastuzumab emantasine (T-DM1)		42 days
Incidence of adverse events in Phase 1a combination with T-DM1		24 months
incidence of laboratory abnormalities in Phase 1a combination with T-DM1

Secondary Outcomes

Measure	Description	Time Frame
Objective Response rate in Phase 1a monotherapy	For patients with measurable disease at baseline, confirmed response per RECIST 1.1	24 months
Objective response rate in Phase 1b monotherapy

Eligibility Module

Eligibility Criteria

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)

Facility	Status	City	State	ZIP	Country	Contacts
University of Colorado - Anschutz Medical Campus - PPDS		Aurora	Colorado	80045	United States
Advent Health Orlando

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
D008453	Maytansine
D018942	Macrolides
D007783	Lactones
D009930	Organic Chemicals
D047029	Lactams, Macrocyclic
D047028	Macrocyclic Compounds
D011083	Polycyclic Compounds
D000068878	Trastuzumab
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins