ELVN-002 With Trastuzumab +/- Chemotherapy in HER2+ Solid Tumors, Colorectal and Breast Cancer

NCT ID: NCT06328738

Last Updated: 2025-11-19

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 275 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-30
• Study Completion Date: 2028-07-31

Brief Summary

The purpose of this study is to determine the safety, tolerability, and recommended dose of ELVN-002 in combination with trastuzumab in participants with advanced-stage HER2-positive tumors and in combination with trastuzumab, and chemotherapy in participants with advanced-stage HER2-positive colorectal cancer and breast cancer.

Detailed Description

Parts 1 and 3 of this study are designed to evaluate preliminary safety, tolerability, and pharmacokinetics (PK) of ELVN-002 in combination with trastuzumab in participants with advanced stage HER2 positive solid tumors. In addition, Part 3 will evaluate the preliminary efficacy of ELVN-002 in combination with trastuzumab in participants with advanced-stage HER2-positive solid tumors.

Part 2 of this study will evaluate the preliminary safety, tolerability, and PK of ELVN-002 in combination with trastuzumab and chemotherapy; capecitabine and oxaliplatin(CAPEOX) or 5-fluorouracil (5-FU), leucovorin (LCV) and oxaliplatin (mFOLFOX6) in participants with advanced stage HER2 positive colorectal cancer, or eribulin or capecitabine in participants with advanced-stage HER2-positive breast cancer, or paclitaxel in participants with advanced stage solid tumors.

In part 4, the preliminary safety, tolerability, PK, and efficacy of ELVN-002 in combination with trastuzumab and CAPEOX or mFOLFOX6 will be evaluated in participants with HER2-positive colorectal cancer.

Conditions

HER2-positive Breast Cancer; HER2-positive Gastric Cancer; HER2 Positive Solid Tumors; HER2 Amplification; Colorectal Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: ELVN-002 + trastuzumab dose escalation

ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+.

Group Type: EXPERIMENTAL

ELVN-002

Intervention Type: DRUG

capsule

Trastuzumab

Intervention Type: DRUG

intravenous

Part 2A: ELVN-002 + trastuzumab + CAPEOX dose escalation in colorectal cancer

ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Capecitabine will be administered orally twice daily at 1000 mg/m2 on days 1 - 14 of a 21-day cycle. Oxaliplatin will be administered intravenously at 130 mg/m2 on day 1 of a 21-day cycle.

Group Type: EXPERIMENTAL

ELVN-002

Intervention Type: DRUG

capsule

Trastuzumab

Intervention Type: DRUG

intravenous

Oxaliplatin

Intervention Type: DRUG

intravenous

Capecitabine

Intervention Type: DRUG

capsule

Part 2B: ELVN-002 + trastuzumab + mFOLFOX6 dose escalation in colorectal cancer

ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered intravenously at 6 mg/kg IV cycle 1, day 2 followed by 4 mg/kg IV cycle 1, day 15, and then one dose at 4mg/kg IV every 14 days. Fluorouracil (5-FU) will be administered intravenously as a 400 mg/m2 IV bolus on days 1 and 15 followed by 2400 mg/m2 over 46-48 hours of continuous infusion on days 1-3 and days 15-17 of a 28-day cycle. Leucovorin will be administered intravenously at 400 mg/m2 concurrently with oxaliplatin on days 1 and 15 of a 28-day cycle. Oxaliplatin will be administered intravenously at 85 mg/m2 IV on day 1 and 15 of a 28-day cycle.

Group Type: EXPERIMENTAL

ELVN-002

Intervention Type: DRUG

capsule

Trastuzumab

Intervention Type: DRUG

intravenous

5-Fluorouracil

Intervention Type: DRUG

intravenous

Oxaliplatin

Intervention Type: DRUG

intravenous

Leucovorin

Intervention Type: DRUG

intravenous

Part 2C: ELVN-002 + trastuzumab + capecitabine dose escalation in breast cancer

ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Capecitabine will be administered orally twice daily at 1000 mg/m2 on days 1 - 14 of a 21-day cycle.

Group Type: EXPERIMENTAL

ELVN-002

Intervention Type: DRUG

capsule

Trastuzumab

Intervention Type: DRUG

intravenous

Capecitabine

Intervention Type: DRUG

capsule

Part 2D: ELVN-002 + trastuzumab + paclitaxel dose escalation in solid tumors

ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Paclitaxel will be administered intravenously at 80 mg/m2 on days 1, 8, and 15 of a 21-day cycle.

Group Type: EXPERIMENTAL

ELVN-002

Intervention Type: DRUG

capsule

Trastuzumab

Intervention Type: DRUG

intravenous

paclitaxel

Intervention Type: DRUG

intravenous

Part 2E: ELVN-002 + trastuzumab + eribulin dose escalation in breast cancer

ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Eribulin will be administered intravenously at 1.4 mg/m2 on days 1 and 8 of a 21-day cycle.

Group Type: EXPERIMENTAL

ELVN-002

Intervention Type: DRUG

capsule

Trastuzumab

Intervention Type: DRUG

intravenous

Eribulin

Intervention Type: DRUG

intravenous

Part 3A: ELVN-002 + trastuzumab dose expansion in colorectal cancer

ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+

Group Type: EXPERIMENTAL

ELVN-002

Intervention Type: DRUG

capsule

Trastuzumab

Intervention Type: DRUG

intravenous

Part 3B: ELVN-002 + trastuzumab dose expansion in breast cancer

ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+.

Group Type: EXPERIMENTAL

ELVN-002

Intervention Type: DRUG

capsule

Trastuzumab

Intervention Type: DRUG

intravenous

Part 3C: ELVN-002 + trastuzumab dose expansion in other solid tumor type 1

ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+.

Group Type: EXPERIMENTAL

ELVN-002

Intervention Type: DRUG

capsule

Trastuzumab

Intervention Type: DRUG

intravenous

Part 3D: ELVN-002 + trastuzumab dose expansion in other solid tumor type 2

ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+.

Group Type: EXPERIMENTAL

ELVN-002

Intervention Type: DRUG

capsule

Trastuzumab

Intervention Type: DRUG

intravenous

Part 3E: ELVN-002 + trastuzumab dose expansion in other solid tumor type 3

ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+.

Group Type: EXPERIMENTAL

ELVN-002

Intervention Type: DRUG

capsule

Trastuzumab

Intervention Type: DRUG

intravenous

Part 4A: ELVN-002 + trastuzumab + CAPEOX dose expansion in colorectal cancer

ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Capecitabine will be administered orally twice daily at 1000 mg/m2 on Days 1 - 14 of a 21-day cycle. Oxaliplatin: will be administered intravenously at 130 mg/m2 on Day 1 of a 21-day cycle.

Group Type: EXPERIMENTAL

ELVN-002

Intervention Type: DRUG

capsule

Trastuzumab

Intervention Type: DRUG

intravenous

Oxaliplatin

Intervention Type: DRUG

intravenous

Capecitabine

Intervention Type: DRUG

capsule

Part 4B: ELVN-002 + trastuzumab + mFOLFOX6 dose expansion in colorectal cancer

ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered intravenously at 6 mg/kg IV cycle 1, day 2 followed by 4 mg/kg IV cycle 1, day 15, and then one dose at 4mg/kg IV every 14 days. Fluorouracil (5-FU) will be administered intravenously as a 400 mg/m2 IV bolus on days 1 and 15 followed by 2400 mg/m2 over 46-48 hours of continuous infusion on days 1-3 and days 15-17 of a 28-day cycle. Leucovorin will be administered intravenously at 400 mg/m2 concurrently with oxaliplatin on days 1 and 15 of a 28-day cycle. Oxaliplatin will be administered intravenously at 85 mg/m2 IV on days 1 and 15 of a 28-day cycle.

Group Type: EXPERIMENTAL

ELVN-002

Intervention Type: DRUG

capsule

Trastuzumab

Intervention Type: DRUG

intravenous

5-Fluorouracil

Intervention Type: DRUG

intravenous

Oxaliplatin

Intervention Type: DRUG

intravenous

Leucovorin

Intervention Type: DRUG

intravenous

Interventions

ELVN-002

capsule

Intervention Type: DRUG

Trastuzumab

intravenous

Intervention Type: DRUG

5-Fluorouracil

intravenous

Intervention Type: DRUG

Oxaliplatin

intravenous

Intervention Type: DRUG

Capecitabine

capsule

Intervention Type: DRUG

Eribulin

intravenous

Intervention Type: DRUG

paclitaxel

intravenous

Intervention Type: DRUG

Leucovorin

intravenous

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Pathologically or histologically documented solid tumor.
• Locally advanced or relapsed/refractory disease or unresectable metastatic disease.
• HER2-positive disease based on the following local testing:

• Colorectal cancer: IHC3+, IHC2+/ISH+, NGS amplification by tissue (no RAS or BRAF mutation allowed)
• Breast cancer: IHC3+ or IHC2+/ISH+ by tissue
• Gastric cancer: IHC3+ or IHC2+/ISH+ by tissue
• Other cancers: IHC3+, IHC2+/ISH+, NGS amplification by tissue or ctDNA
• Prior therapies for Part 1 (Dose Escalation ELVN-002 + trastuzumab):

• Colorectal cancer: treated with prior fluoropyrimidine, oxaliplatin, irinotecan-based regimens, anti-epidermal growth factor receptor (EGFR) treatment (if clinically indicated), anti-vascular endothelial growth factor (VEGF) treatment (if clinically indicated), and an anti-programmed death ligand 1 (PD-(L)-1) treatment (if the tumor is microsatellite instability (MSI)-high/deficient mismatch repair (dMMR)
• Breast cancer: treated with prior taxane, pertuzumab, trastuzumab, and fam-trastuzumab deruxtecan (T-DXd) if available and appropriate based on local standard of care and investigator's assessment
• Gastric cancer: treated with trastuzumab/platinum fluorouracil containing regimen and T-DXd.
• Other cancers: progressed during or after ≥ 1 prior line of systemic therapy for locally advanced unresectable or metastatic disease
• Prior HER2 targeted therapy is allowed
• Prior therapies for Part 2 (Phase 1a Dose Escalation ELVN-002 + trastuzumab + chemotherapy):

• Colorectal cancer: candidate for CAPEOX (capecitabine and oxaliplatin) or mFOLFOX6 (5-FU, LCV and oxaliplatin), and treated, if clinically indicated, with an anti-programmed death ligand 1 (PD-(L)-1) treatment (if the tumor is microsatellite instability (MSI)-high/deficient mismatch repair (dMMR). Prior HER2 targeted therapy is allowed.
• Breast cancer: candidate for capecitabine, paclitaxel or eribulin, and treated with prior taxane, pertuzumab, trastuzumab, and T-DXd, if available and appropriate, based on local standard of care and investigator's assessment. No prior HER2 targeted tyrosine kinase inhibitor therapy (antibody-drug conjugates and antibodies are allowed), no prior capecitabine (for the capecitabine cohort), no prior eribulin (for the eribulin cohort), and no taxane as immediate prior therapy (paclitaxel cohort).
• Prior therapies for Part 3 (Phase 1b Dose Expansion ELVN-002 + trastuzumab):

• Colorectal cancer: treated with prior fluoropyrimidine, oxaliplatin, irinotecan-based regimens, anti-epidermal growth factor receptor (EGFR) treatment (if clinically indicated), anti-vascular endothelial growth factor (VEGF) treatment (if clinically indicated), and an anti-programmed death ligand 1 (PD-(L)-1) treatment if the tumor is microsatellite instability (MSI)-high/deficient mismatch repair (dMMR). No prior HER2 targeted therapy.
• Breast cancer: treated with prior taxane, pertuzumab, trastuzumab, and T-DXd if available and appropriate based on local standard of care and investigator's assessment. No prior HER2 targeted tyrosine kinase inhibitor therapy (antibody-drug conjugates and antibodies are allowed).
• Gastric cancer: treated with prior trastuzumab/platinum fluorouracil containing regimen and T-DXd. No prior HER2 targeted therapy.
• Other cancers: Progressed during or after ≥ 1 prior line of systemic therapy for locally advanced unresectable or metastatic disease. No prior HER2 targeted therapy.
• Prior therapies for Part 4 (Phase 1b Dose Expansion ELVN-002 + trastuzumab + chemotherapy):

• Colorectal cancer: candidate for CAPEOX or mFOLFOX6 and not a candidate for first-line anti-programmed death ligand 1 (PD-(L)-1) treatment (if the tumor is microsatellite instability (MSI)-high/deficient mismatch repair (dMMR). No prior therapy for metastatic disease (1 cycle of mFOLFOX6 or 1 cycle of CAPEOX allowed). No prior HER2 targeted therapy.
• At least 1 measurable lesion based on RECIST v 1.1 within 6 weeks before the first dose of ELVN-002 (Part 3 and Part 4 only; Phase 1b Dose Expansion cohorts)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Adequate hematological, hepatic, renal, and cardiac function

Exclusion Criteria

• Treatment with anticancer therapy within a specific time before the first dose:

• Chemotherapy (including ADC) ≤ 3 weeks
• Immunotherapy ≤ 4 weeks
• Hormonal therapy ≤ 2 weeks
• TKI ≤ 2 weeks
• Any experimental therapy ≤ 3 weeks or 5 half-lives, whichever is longer
• Radiotherapy-wide therapy ≤ 3 weeks
• Radiotherapy limited field (including stereotactic brain) ≤ 2 weeks
• Antibody ≤ 3 weeks
• Any brain lesion requiring immediate local therapy
• Ongoing use of corticosteroids for central nervous system (CNS) symptoms at a dose of > 2 mg daily of dexamethasone (or equivalent)
• Leptomeningeal disease
• Uncontrolled seizures
• Participants for any chemotherapy cohort: ongoing Grade 2 or higher neuropathy of any cause
• Inability to swallow pills or any significant gastrointestinal disease that would preclude adequate oral absorption of medications.
• Ongoing adverse effects from prior treatment > CTCAE Grade 1 except for Grade 2 alopecia
• Corrected QT interval (QTc) of >470 milliseconds (ms) for females or >450 ms for males

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Enliven Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

BRCR Medical Center Inc.

Plantation, Florida, United States

Washington University

St Louis, Missouri, United States

NEXT Virginia

Fairfax, Virginia, United States

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

CHU de Liège

Liège, , Belgium

GZA Ziekenhuizen - Campus Sint-Augustinus

Wilrijk, , Belgium

Institut du Cancer de Montpellier - Val D'Aurelle

Montpellier, , France

CHU de Poitiers

Poitiers, , France

Institut de Cancérologie de l'Ouest

Saint-Herblain, , France

Institut de Cancérologie Strasbourg Europe

Strasbourg, , France

Azienda Ospedaliero-Universitaria Renato Dulbecco

Catanzaro, , Italy

Istituto Europeo di Oncologia

Milan, , Italy

Fondazione IRCCS San Gerardo dei Tintori

Monza, , Italy

Azienda Ospedaliero Universitaria Pisana

Pisa, , Italy

Azienda USL IRCCS di Reggio Emilia

Reggio Emilia, , Italy

Fondazione Policlinico A. Gemelli IRCCS

Rome, , Italy

Radboud UMC

Nijmegen, , Netherlands

CHA Bundang Medical Center

Seongnam-si, , South Korea

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Seoul National University Hospital

Soeul, , South Korea

The Catholic University of Korea, St. Vincent's Hospital

Suwon, , South Korea

NEXT Oncology-Hospital Quironsalud Barcelona

Barcelona, , Spain

START Barcelona_HM Nou Delfos

Barcelona, , Spain

Hospital Universitari Dexeus - Grupo Quironsalud

Barcelona, , Spain

Instituto de Investigacion Oncologica Vall d'Hebron (VHIO) - EPON

Barcelona, , Spain

Hospital Beata Maria Ana

Madrid, , Spain

Clinica universitaria Navarra - Madrid

Madrid, , Spain

START Madrid - Hospital Universitario Fundacion Jimenez Diaz

Madrid, , Spain

Clinica univeritaria Navarra - Pamplonas

Pamplona, , Spain

Fundacion Instituto Valenciano de Oncologia

Valencia, , Spain

Countries

United States; Belgium; France; Italy; Netherlands; South Korea; Spain

Other Identifiers

ELVN-002-003

Identifier Type: -

Identifier Source: org_study_id