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Combination of ELVN-002 and Trastuzumab for HER2-positive Cancers

A Phase 1a/1b Study of ELVN-002 Combined with Trastuzumab in Advanced Stage HER2+ Solid Tumors, and ELVN-002 Combined with Trastuzumab and Chemotherapy in Advanced Stage HER2+ Colorectal Cancer and Breast Cancer

PHASE1 · Enliven Therapeutics · NCT06328738

This study is testing if a new drug called ELVN-002 can safely work together with trastuzumab and chemotherapy to help people with advanced HER2-positive cancers like breast and colorectal cancer.

Quick facts

PhasePHASE1
Study typeInterventional
Enrollment275 (estimated)
Ages18 Years and up
SexAll
SponsorEnliven Therapeutics (industry)
Drugs / interventionstrastuzumab, pertuzumab, chemotherapy, Immunotherapy
Locations31 sites (Plantation, Florida and 30 other locations)
Trial IDNCT06328738 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety, tolerability, and recommended dosage of ELVN-002 when used alongside trastuzumab in patients with advanced-stage HER2-positive solid tumors, including breast and colorectal cancers. It consists of multiple parts, with some assessing the combination of ELVN-002, trastuzumab, and chemotherapy agents like capecitabine and oxaliplatin. The study aims to gather preliminary data on the pharmacokinetics and efficacy of these combinations in treating HER2-positive tumors.

Who should consider this trial

Good fit: Ideal candidates include individuals with advanced-stage HER2-positive solid tumors who have previously undergone standard treatments.

Not a fit: Patients with HER2-negative tumors or those who have not been previously treated for their advanced-stage cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced HER2-positive cancers.

How similar studies have performed: Other studies have shown promising results with similar combinations of HER2-targeted therapies, suggesting potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion 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

Where this trial is running

Plantation, Florida and 30 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: HER2-positive Breast Cancer, HER2-positive Gastric Cancer, HER2 Positive Solid Tumors, HER2 Amplification, Colorectal Cancer, ELVN-002, HER2 positive Colorectal Cancer, HER2 overexpression

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.