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

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

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