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

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06328738
• Other study ID #: ELVN-002-003
• Status: Recruiting
• Phase: Phase 1
• Start date: June 1, 2024
• Est. completion date: July 2028

Study information

• Verified date: March 2024
• Source: Enliven Therapeutics
• Contact: Helen L Collins, MD
• Phone: 7077993272
• Email: helen.collins[@]enliventherapeutics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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, capecitabine, or paclitaxel in participants with advanced-stage HER2-positive breast cancer. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 255
• Est. completion date: July 2028
• Est. primary completion date: January 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Colorectal Cancer
• Colorectal Neoplasms
• HER2 Positive Solid Tumors
• HER2-positive Breast Cancer
• HER2-positive Gastric Cancer

Intervention

Drug:
• ELVN-002
capsule
• Trastuzumab
intravenous
• 5-Fluorouracil
intravenous
• Oxaliplatin
intravenous
• Capecitabine
capsule
• Eribulin
intravenous
• paclitaxel
intravenous
• Leucovorin
intravenous

Locations

Country	Name	City	State
United States	NEXT Virginia	Fairfax	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Enliven Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose limiting toxicities (DLTs; Phase 1a only)	DLTs will be used to support that the recommended doses for expansion are	21 days
Primary	Incidence of adverse events (AEs)	AEs will be used to support that the recommended doses for expansion are likely to be tolerable	24 months
Primary	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
Primary	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	PK parameter of area under the curve of ELVN-002 (Phase 1a only)	The concentration of ELVN-002 measured in the blood over 24 hours at steady state	24 months
Secondary	PK parameter of maximum concentration of ELVN-002 (Phase 1a only)	The maximum concentration of ELVN-002 measured in the blood at any time point at steady state	24 months
Secondary	PK parameter of minimum concentration of ELVN-002 (Phase 1a only)	The minimum concentration of ELVN-002 measured in the blood at any time point at steady	24 months
Secondary	PK parameter of terminal half life of ELVN-002 (Phase 1a only)	The half life of ELVN-002 calculated from the concentration of ELVN-002 measured in blood	24 months
Secondary	Confirmed objective response rate (ORR)	For patients with measurable disease at baseline, confirmed response as assessed by investigator per RECIST v1.1	24 months
Secondary	Duration of response (DOR; Phase 1b only)	The time from the first response to progression or death per RECIST v1.1	24 months
Secondary	Brain metastases response (Phase 1b only)	For patients with measurable brain metastases at baseline, the percent of patients who have a confirmed response per RECIST v1.1	24 months