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

NCT06328738 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: ELVN-002-003
• Study Type: interventional
• Target: 275
• Locations: 7 countries
• Sites: 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.

Conditions

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

Keywords

ELVN-002; HER2 positive Colorectal Cancer; HER2 overexpression; HER2

Outcome Measures

Primary Outcomes (4)

• Incidence of dose limiting toxicities (DLTs; Phase 1a only)

  DLTs will be used to support that the recommended doses for expansion are \</= maximum tolerated dose (MTD)

  21 days

• Incidence of adverse events (AEs)

  AEs will be used to support that the recommended doses for expansion are likely to be tolerable

  24 months

• Incidence of laboratory abnormalities

  Clinically significant laboratory abnormalities will be used to support that the recommended doses for expansion are likely to be tolerable

  24 months

• Incidence of electrocardiogram abnormalities

  Clinically significant electrocardiogram abnormalities will be used to support that the recommended doses for expansion are likely to be tolerable

  24 months

Secondary Outcomes (7)

• PK parameter of area under the curve of ELVN-002 (Phase 1a only)

  24 months

• PK parameter of maximum concentration of ELVN-002 (Phase 1a only)

  24 months

• PK parameter of minimum concentration of ELVN-002 (Phase 1a only)

  24 months

• PK parameter of terminal half life of ELVN-002 (Phase 1a only)

  24 months

• Confirmed objective response rate (ORR)

  24 months

Study Arms (13)

Part 1: ELVN-002 + trastuzumab dose escalation

EXPERIMENTAL

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+.

Drug: ELVN-002; Drug: Trastuzumab

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

EXPERIMENTAL

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.

Drug: ELVN-002; Drug: Trastuzumab; Drug: Oxaliplatin; Drug: Capecitabine

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

EXPERIMENTAL

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.

Drug: ELVN-002; Drug: Trastuzumab; Drug: 5-Fluorouracil; Drug: Oxaliplatin; Drug: Leucovorin

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

EXPERIMENTAL

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.

Drug: ELVN-002; Drug: Trastuzumab; Drug: Capecitabine

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

EXPERIMENTAL

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.

Drug: ELVN-002; Drug: Trastuzumab; Drug: paclitaxel

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

EXPERIMENTAL

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.

Drug: ELVN-002; Drug: Trastuzumab; Drug: Eribulin

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

EXPERIMENTAL

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+

Drug: ELVN-002; Drug: Trastuzumab

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

EXPERIMENTAL

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+.

Drug: ELVN-002; Drug: Trastuzumab

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

EXPERIMENTAL

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+.

Drug: ELVN-002; Drug: Trastuzumab

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

EXPERIMENTAL

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+.

Drug: ELVN-002; Drug: Trastuzumab

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

EXPERIMENTAL

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+.

Drug: ELVN-002; Drug: Trastuzumab

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

EXPERIMENTAL

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.

Drug: ELVN-002; Drug: Trastuzumab; Drug: Oxaliplatin; Drug: Capecitabine

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

EXPERIMENTAL

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.

Drug: ELVN-002; Drug: Trastuzumab; Drug: 5-Fluorouracil; Drug: Oxaliplatin; Drug: Leucovorin

Interventions

ELVN-002 DRUG

capsule

Part 1: ELVN-002 + trastuzumab dose escalation; Part 2A: ELVN-002 + trastuzumab + CAPEOX dose escalation in colorectal cancer; Part 2B: ELVN-002 + trastuzumab + mFOLFOX6 dose escalation in colorectal cancer; Part 2C: ELVN-002 + trastuzumab + capecitabine dose escalation in breast cancer; Part 2D: ELVN-002 + trastuzumab + paclitaxel dose escalation in solid tumors; Part 2E: ELVN-002 + trastuzumab + eribulin dose escalation in breast cancer; Part 3A: ELVN-002 + trastuzumab dose expansion in colorectal cancer; Part 3B: ELVN-002 + trastuzumab dose expansion in breast cancer; Part 3C: ELVN-002 + trastuzumab dose expansion in other solid tumor type 1; Part 3D: ELVN-002 + trastuzumab dose expansion in other solid tumor type 2; Part 3E: ELVN-002 + trastuzumab dose expansion in other solid tumor type 3; Part 4A: ELVN-002 + trastuzumab + CAPEOX dose expansion in colorectal cancer; Part 4B: ELVN-002 + trastuzumab + mFOLFOX6 dose expansion in colorectal cancer

Trastuzumab DRUG

intravenous

Part 1: ELVN-002 + trastuzumab dose escalation; Part 2A: ELVN-002 + trastuzumab + CAPEOX dose escalation in colorectal cancer; Part 2B: ELVN-002 + trastuzumab + mFOLFOX6 dose escalation in colorectal cancer; Part 2C: ELVN-002 + trastuzumab + capecitabine dose escalation in breast cancer; Part 2D: ELVN-002 + trastuzumab + paclitaxel dose escalation in solid tumors; Part 2E: ELVN-002 + trastuzumab + eribulin dose escalation in breast cancer; Part 3A: ELVN-002 + trastuzumab dose expansion in colorectal cancer; Part 3B: ELVN-002 + trastuzumab dose expansion in breast cancer; Part 3C: ELVN-002 + trastuzumab dose expansion in other solid tumor type 1; Part 3D: ELVN-002 + trastuzumab dose expansion in other solid tumor type 2; Part 3E: ELVN-002 + trastuzumab dose expansion in other solid tumor type 3; Part 4A: ELVN-002 + trastuzumab + CAPEOX dose expansion in colorectal cancer; Part 4B: ELVN-002 + trastuzumab + mFOLFOX6 dose expansion in colorectal cancer

5-Fluorouracil DRUG

intravenous

Part 2B: ELVN-002 + trastuzumab + mFOLFOX6 dose escalation in colorectal cancer; Part 4B: ELVN-002 + trastuzumab + mFOLFOX6 dose expansion in colorectal cancer

Oxaliplatin DRUG

intravenous

Part 2A: ELVN-002 + trastuzumab + CAPEOX dose escalation in colorectal cancer; Part 2B: ELVN-002 + trastuzumab + mFOLFOX6 dose escalation in colorectal cancer; Part 4A: ELVN-002 + trastuzumab + CAPEOX dose expansion in colorectal cancer; Part 4B: ELVN-002 + trastuzumab + mFOLFOX6 dose expansion in colorectal cancer

Capecitabine DRUG

capsule

Part 2A: ELVN-002 + trastuzumab + CAPEOX dose escalation in colorectal cancer; Part 2C: ELVN-002 + trastuzumab + capecitabine dose escalation in breast cancer; Part 4A: ELVN-002 + trastuzumab + CAPEOX dose expansion in colorectal cancer

Eribulin DRUG

intravenous

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

paclitaxel DRUG

intravenous

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

Leucovorin DRUG

intravenous

Part 2B: ELVN-002 + trastuzumab + mFOLFOX6 dose escalation in colorectal cancer; Part 4B: ELVN-002 + trastuzumab + mFOLFOX6 dose expansion in colorectal cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Enliven Therapeutics: lead

Study Sites (31)

BRCR Medical Center Inc.

Plantation, Florida, 33322, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

NEXT Virginia

Fairfax, Virginia, 22031, United States

Location

Cliniques Universitaires Saint-Luc

Brussels, Belgium

Location

CHU de Liège

Liège, Belgium

Location

GZA Ziekenhuizen - Campus Sint-Augustinus

Wilrijk, Belgium

Location

Institut du Cancer de Montpellier - Val D'Aurelle

Montpellier, 34090, France

Location

CHU de Poitiers

Poitiers, 8600, France

Location

Institut de Cancérologie de l'Ouest

Saint-Herblain, France

Location

Institut de Cancérologie Strasbourg Europe

Strasbourg, 67033, France

Location

Azienda Ospedaliero-Universitaria Renato Dulbecco

Catanzaro, Italy

Location

Istituto Europeo di Oncologia

Milan, Italy

Location

Fondazione IRCCS San Gerardo dei Tintori

Monza, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, Italy

Location

Azienda USL IRCCS di Reggio Emilia

Reggio Emilia, Italy

Location

Fondazione Policlinico A. Gemelli IRCCS

Rome, 00168, Italy

Location

Radboud UMC

Nijmegen, Netherlands

Location

CHA Bundang Medical Center

Seongnam-si, 13496, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Seoul National University Hospital

Soeul, South Korea

Location

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

Suwon, 16247, South Korea

Location

NEXT Oncology-Hospital Quironsalud Barcelona

Barcelona, 08023, Spain

Location

START Barcelona_HM Nou Delfos

Barcelona, 08023, Spain

Location

Hospital Universitari Dexeus - Grupo Quironsalud

Barcelona, Spain

Location

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

Barcelona, Spain

Location

Hospital Beata Maria Ana

Madrid, 28007, Spain

Location

Clinica universitaria Navarra - Madrid

Madrid, 28027, Spain

Location

START Madrid - Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Clinica univeritaria Navarra - Pamplonas

Pamplona, Spain

Location

Fundacion Instituto Valenciano de Oncologia

Valencia, Spain

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Trastuzumab; Fluorouracil; Oxaliplatin; Capecitabine; eribulin; Paclitaxel; Leucovorin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1a will be a dose escalation of ELVN-002 in combination with fixed doses of trastuzumab or trastuzumab + chemotherapy according to the Bayesian Optimal Interval Design model. Phase 1b will be a dose expansion at one or more doses of ELVN-002.

Study Record Dates

• First Submitted: March 10, 2024
• First Posted: March 25, 2024
• Study Start: May 30, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): July 1, 2028
• Last Updated: November 19, 2025

Record last verified: 2025-07

Locations

US (3); NL (1); ES (9); BE (3); FR (4); IT (6); KR (5)