Trial Title:
ELVN-002 with Trastuzumab +/- Chemotherapy in HER2+ Solid Tumors, Colorectal and Breast Cancer
NCT ID:
NCT06328738
Condition:
HER2-positive Breast Cancer
HER2-positive Gastric Cancer
HER2 Positive Solid Tumors
HER2 Amplification
Colorectal Cancer
Conditions: Official terms:
Breast Neoplasms
Colorectal Neoplasms
Leucovorin
Paclitaxel
Capecitabine
Oxaliplatin
Fluorouracil
Trastuzumab
Conditions: Keywords:
ELVN-002
HER2 positive Colorectal Cancer
HER2 overexpression
HER2
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Intervention model description:
Phase 1a will be a dose escalation of ELVN-002 in combination with fixed doses of
trastuzumab or trastuzumab + chemotherapy according to the Bayesian Optimal Interval
Design model. Phase 1b will be a dose expansion at one or more doses of ELVN-002.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
ELVN-002
Description:
capsule
Arm group label:
Part 1: ELVN-002 + trastuzumab dose escalation
Arm group label:
Part 2A: ELVN-002 + trastuzumab + CAPEOX dose escalation in colorectal cancer
Arm group label:
Part 2B: ELVN-002 + trastuzumab + mFOLFOX6 dose escalation in colorectal cancer
Arm group label:
Part 2C: ELVN-002 + trastuzumab + capecitabine dose escalation in breast cancer
Arm group label:
Part 2D: ELVN-002 + trastuzumab + paclitaxel dose escalation in breast cancer
Arm group label:
Part 2E: ELVN-002 + trastuzumab + eribulin dose escalation in breast cancer
Arm group label:
Part 3A: ELVN-002 + trastuzumab dose expansion in colorectal cancer
Arm group label:
Part 3B: ELVN-002 + trastuzumab dose expansion in breast cancer
Arm group label:
Part 3C: ELVN-002 + trastuzumab dose expansion in other solid tumor type 1
Arm group label:
Part 3D: ELVN-002 + trastuzumab dose expansion in other solid tumor type 2
Arm group label:
Part 3E: ELVN-002 + trastuzumab dose expansion in other solid tumor type 3
Arm group label:
Part 4A: ELVN-002 + trastuzumab + CAPEOX dose expansion in colorectal cancer
Arm group label:
Part 4B: ELVN-002 + trastuzumab + mFOLFOX6 dose expansion in colorectal cancer
Intervention type:
Drug
Intervention name:
Trastuzumab
Description:
intravenous
Arm group label:
Part 1: ELVN-002 + trastuzumab dose escalation
Arm group label:
Part 2A: ELVN-002 + trastuzumab + CAPEOX dose escalation in colorectal cancer
Arm group label:
Part 2B: ELVN-002 + trastuzumab + mFOLFOX6 dose escalation in colorectal cancer
Arm group label:
Part 2C: ELVN-002 + trastuzumab + capecitabine dose escalation in breast cancer
Arm group label:
Part 2D: ELVN-002 + trastuzumab + paclitaxel dose escalation in breast cancer
Arm group label:
Part 2E: ELVN-002 + trastuzumab + eribulin dose escalation in breast cancer
Arm group label:
Part 3A: ELVN-002 + trastuzumab dose expansion in colorectal cancer
Arm group label:
Part 3B: ELVN-002 + trastuzumab dose expansion in breast cancer
Arm group label:
Part 3C: ELVN-002 + trastuzumab dose expansion in other solid tumor type 1
Arm group label:
Part 3D: ELVN-002 + trastuzumab dose expansion in other solid tumor type 2
Arm group label:
Part 3E: ELVN-002 + trastuzumab dose expansion in other solid tumor type 3
Arm group label:
Part 4A: ELVN-002 + trastuzumab + CAPEOX dose expansion in colorectal cancer
Arm group label:
Part 4B: ELVN-002 + trastuzumab + mFOLFOX6 dose expansion in colorectal cancer
Intervention type:
Drug
Intervention name:
5-Fluorouracil
Description:
intravenous
Arm group label:
Part 2B: ELVN-002 + trastuzumab + mFOLFOX6 dose escalation in colorectal cancer
Arm group label:
Part 4B: ELVN-002 + trastuzumab + mFOLFOX6 dose expansion in colorectal cancer
Intervention type:
Drug
Intervention name:
Oxaliplatin
Description:
intravenous
Arm group label:
Part 2A: ELVN-002 + trastuzumab + CAPEOX dose escalation in colorectal cancer
Arm group label:
Part 2B: ELVN-002 + trastuzumab + mFOLFOX6 dose escalation in colorectal cancer
Arm group label:
Part 4A: ELVN-002 + trastuzumab + CAPEOX dose expansion in colorectal cancer
Arm group label:
Part 4B: ELVN-002 + trastuzumab + mFOLFOX6 dose expansion in colorectal cancer
Intervention type:
Drug
Intervention name:
Capecitabine
Description:
capsule
Arm group label:
Part 2A: ELVN-002 + trastuzumab + CAPEOX dose escalation in colorectal cancer
Arm group label:
Part 2C: ELVN-002 + trastuzumab + capecitabine dose escalation in breast cancer
Arm group label:
Part 4A: ELVN-002 + trastuzumab + CAPEOX dose expansion in colorectal cancer
Intervention type:
Drug
Intervention name:
Eribulin
Description:
intravenous
Arm group label:
Part 2E: ELVN-002 + trastuzumab + eribulin dose escalation in breast cancer
Intervention type:
Drug
Intervention name:
paclitaxel
Description:
intravenous
Arm group label:
Part 2D: ELVN-002 + trastuzumab + paclitaxel dose escalation in breast cancer
Intervention type:
Drug
Intervention name:
Leucovorin
Description:
intravenous
Arm group label:
Part 2B: ELVN-002 + trastuzumab + mFOLFOX6 dose escalation in colorectal cancer
Arm group label:
Part 4B: ELVN-002 + trastuzumab + mFOLFOX6 dose expansion in colorectal cancer
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.
Detailed 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.
Criteria for eligibility:
Criteria:
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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
BRCR Medical Center Inc.
Address:
City:
Plantation
Zip:
33322
Country:
United States
Status:
Recruiting
Contact:
Last name:
Harshad V. Amin, M.D.
Facility:
Name:
Washington University
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Status:
Recruiting
Contact:
Last name:
Faisal Fa'ak, MD
Facility:
Name:
NEXT Virginia
Address:
City:
Fairfax
Zip:
22031
Country:
United States
Status:
Recruiting
Contact:
Last name:
Alexander Spira, MD
Phone:
703.636.1473
Facility:
Name:
Cliniques Universitaires Saint-Luc
Address:
City:
Brussels
Country:
Belgium
Status:
Recruiting
Contact:
Last name:
Astrid De Cuyper, MD
Facility:
Name:
CHU de Liège
Address:
City:
Liège
Country:
Belgium
Status:
Recruiting
Contact:
Last name:
Pierre Frères, MD
Facility:
Name:
GZA Ziekenhuizen - Campus Sint-Augustinus
Address:
City:
Wilrijk
Country:
Belgium
Status:
Recruiting
Contact:
Last name:
Tom Van den Mooter, MD
Facility:
Name:
Institut du Cancer de Montpellier - Val D'Aurelle
Address:
City:
Montpellier
Zip:
34090
Country:
France
Status:
Recruiting
Contact:
Last name:
Diego Tosi, MD
Facility:
Name:
CHU de Poitiers
Address:
City:
Poitiers
Zip:
8600
Country:
France
Status:
Recruiting
Contact:
Last name:
Nicolas Isambert, MD
Facility:
Name:
Institut de Cancérologie de l'Ouest
Address:
City:
Saint-Herblain
Country:
France
Status:
Recruiting
Contact:
Last name:
Marie Robert, MD
Facility:
Name:
Institut de Cancérologie Strasbourg Europe
Address:
City:
Strasbourg
Zip:
67033
Country:
France
Status:
Recruiting
Contact:
Last name:
Lauriane Eberst, MD
Facility:
Name:
Istituto Europeo di Oncologia
Address:
City:
Milan
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Giuseppe Curigliano, MD
Facility:
Name:
Fondazione IRCCS San Gerardo dei Tintori
Address:
City:
Monza
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Marina Elena Cazzaniga, MD
Facility:
Name:
Azienda Ospedaliero Universitaria Pisana
Address:
City:
Pisa
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Chiara Cremolini, MD
Facility:
Name:
Fondazione Policlinico A. Gemelli IRCCS
Address:
City:
Rome
Zip:
00168
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Gennaro Daniele, MD
Facility:
Name:
CHA Bundang Medical Center
Address:
City:
Seongnam-si
Zip:
13496
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Yong Wha Moon, M.D.
Facility:
Name:
Severance Hospital, Yonsei University Health System
Address:
City:
Seoul
Zip:
03722
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Joohyuk Sohn, M.D.
Facility:
Name:
Asan Medical Center
Address:
City:
Seoul
Zip:
05505
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Jeong Eun Kim, M.D.
Facility:
Name:
Seoul National University Hospital
Address:
City:
Soeul
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Seock-Ah Im
Facility:
Name:
The Catholic University of Korea, St. Vincent's Hospital
Address:
City:
Suwon
Zip:
16247
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Hyung Soon Park, M.D.
Facility:
Name:
Radboud UMC
Address:
City:
Nijmegen
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Carla Van Herpen, MD
Facility:
Name:
NEXT Oncology-Hospital Quironsalud Barcelona
Address:
City:
Barcelona
Zip:
08023
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Fabricio Racca, MD
Facility:
Name:
START Barcelona_HM Nou Delfos
Address:
City:
Barcelona
Zip:
08023
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Tatiana Hernández Guerrero, MD
Facility:
Name:
Hospital Universitari Dexeus - Grupo Quironsalud
Address:
City:
Barcelona
Country:
Spain
Status:
Recruiting
Contact:
Last name:
José Manuel Pérez García, MD
Facility:
Name:
Instituto de Investigacion Oncologica Vall d'Hebron (VHIO) - EPON
Address:
City:
Barcelona
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Alonso Casal Guzman, MD
Facility:
Name:
Hospital Beata Maria Ana
Address:
City:
Madrid
Zip:
28007
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Javier Cortes, MD
Facility:
Name:
Clinica universitaria Navarra - Madrid
Address:
City:
Madrid
Zip:
28027
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Ignacio Matos, MD
Facility:
Name:
START Madrid - Hospital Universitario Fundacion Jimenez Diaz
Address:
City:
Madrid
Zip:
28040
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Bernard Doger, MD
Facility:
Name:
Clinica univeritaria Navarra - Pamplonas
Address:
City:
Pamplona
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Ignacio Matos, MD
Facility:
Name:
Fundacion Instituto Valenciano de Oncologia
Address:
City:
Valencia
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Marcos Melian, MD
Start date:
May 30, 2024
Completion date:
July 2028
Lead sponsor:
Agency:
Enliven Therapeutics
Agency class:
Industry
Source:
Enliven Therapeutics
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06328738