ELVN-002-003 - 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

Studio Clinico

Patologia: Neoplasie della mammella, Tumori del colon retto, Altre neoplasie

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: No

Fase di studio: 1, I A, I B

Linee di trattamento: Seconda linea, Terza/N linea

Criteri di inclusione: 

- 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.

Criteri di esclusione: 

- 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.

Trattamento sperimentale: 

ELVN-002

Trattamento di controllo: 

NA

Centri partecipanti

Nord Italia

Centro Italia

Sud Italia e isole

Informazioni Generali

Protocollo

Numero di iscrizione a registro: NCT06328738

Data di inserimento: 12.03.2025

Promotore

Enliven Therapeutics

Principal Investigator ITALIA

Riferimento: Dr. Info non applicabile

Telefono: 00000

Email: na@na.it

Localita: na