ACTIVE_NOT_RECRUITING

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

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 HER2

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2024-05-30

Study Completion:2028-07

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT06328738

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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): * 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	* 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

Inclusion Criteria

Exclusion 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):
* 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

* 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

Contacts and Locations

Study Locations (Sites)

BRCR Medical Center Inc.

Plantation, Florida, 33322

United States

Washington University

Saint Louis, Missouri, 63110

United States

NEXT Virginia

Fairfax, Virginia, 22031

United States

Collaborators and Investigators

Sponsor: Enliven Therapeutics

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-05-30

Study Completion Date2028-07

Study Record Updates

Study Start Date2024-05-30

Study Completion Date2028-07

Terms related to this study

Keywords Provided by Researchers

ELVN-002
HER2 positive Colorectal Cancer
HER2 overexpression
HER2

Additional Relevant MeSH Terms

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