Active, not recruiting
Phase 1
ELVN-002 With Trastuzumab +/- Chemotherapy in HER2+ Solid Tumors, Colorectal and Breast Cancer
Condition(s) studied
HER2-positive Breast CancerHER2-positive Gastric CancerHER2 Positive Solid TumorsHER2 AmplificationColorectal Cancer
Investigational drug(s) / intervention(s)
ELVN-002: capsule
Trastuzumab: intravenous
5-Fluorouracil: intravenous
Oxaliplatin: intravenous
Capecitabine: capsule
Eribulin: intravenous
paclitaxel: intravenous
Leucovorin: intravenous
Study 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.
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
Primary outcome measure(s)
- Incidence of dose limiting toxicities (DLTs; Phase 1a only) — 21 days
DLTs will be used to support that the recommended doses for expansion are \</= maximum tolerated dose (MTD)
- Incidence of adverse events (AEs) — 24 months
AEs will be used to support that the recommended doses for expansion are likely to be tolerable
- Incidence of laboratory abnormalities — 24 months
Clinically significant laboratory abnormalities will be used to support that the recommended doses for expansion are likely to be tolerable
- Incidence of electrocardiogram abnormalities — 24 months
Clinically significant electrocardiogram abnormalities will be used to support that the recommended doses for expansion are likely to be tolerable
Trial sites (31)
| Facility | City | Region | Status |
| BRCR Medical Center Inc. |
Plantation |
Florida |
|
| Washington University |
St Louis |
Missouri |
|
| NEXT Virginia |
Fairfax |
Virginia |
|
| Cliniques Universitaires Saint-Luc |
Brussels |
Belgium |
|
| CHU de Liège |
Liège |
Belgium |
|
| GZA Ziekenhuizen - Campus Sint-Augustinus |
Wilrijk |
Belgium |
|
| Institut du Cancer de Montpellier - Val D'Aurelle |
Montpellier |
France |
|
| CHU de Poitiers |
Poitiers |
France |
|
| Institut de Cancérologie de l'Ouest |
Saint-Herblain |
France |
|
| Institut de Cancérologie Strasbourg Europe |
Strasbourg |
France |
|
| Azienda Ospedaliero-Universitaria Renato Dulbecco |
Catanzaro |
Italy |
|
| Istituto Europeo di Oncologia |
Milan |
Italy |
|
| Fondazione IRCCS San Gerardo dei Tintori |
Monza |
Italy |
|
| Azienda Ospedaliero Universitaria Pisana |
Pisa |
Italy |
|
| Azienda USL IRCCS di Reggio Emilia |
Reggio Emilia |
Italy |
|
| Fondazione Policlinico A. Gemelli IRCCS |
Rome |
Italy |
|
| Radboud UMC |
Nijmegen |
Netherlands |
|
| CHA Bundang Medical Center |
Seongnam-si |
South Korea |
|
| Severance Hospital, Yonsei University Health System |
Seoul |
South Korea |
|
| Asan Medical Center |
Seoul |
South Korea |
|
| Seoul National University Hospital |
Soeul |
South Korea |
|
| The Catholic University of Korea, St. Vincent's Hospital |
Suwon |
South Korea |
|
| NEXT Oncology-Hospital Quironsalud Barcelona |
Barcelona |
Spain |
|
| START Barcelona_HM Nou Delfos |
Barcelona |
Spain |
|
| Hospital Universitari Dexeus - Grupo Quironsalud |
Barcelona |
Spain |
|
| Instituto de Investigacion Oncologica Vall d'Hebron (VHIO) - EPON |
Barcelona |
Spain |
|
| Hospital Beata Maria Ana |
Madrid |
Spain |
|
| Clinica universitaria Navarra - Madrid |
Madrid |
Spain |
|
| START Madrid - Hospital Universitario Fundacion Jimenez Diaz |
Madrid |
Spain |
|
| Clinica univeritaria Navarra - Pamplonas |
Pamplona |
Spain |
|
| Fundacion Instituto Valenciano de Oncologia |
Valencia |
Spain |
|
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