ELVN-002 with Trastuzumab +/- Chemotherapy in HER2+ Solid Tumors, Colorectal and Breast Cancer
- Conditions
- HER2-positive Gastric CancerColorectal CancerHER2 AmplificationHER2-positive Breast CancerHER2 Positive Solid Tumors
- Interventions
- Registration Number
- NCT06328738
- Lead Sponsor
- Enliven Therapeutics
- Brief 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 or capecitabine in participants with advanced-stage HER2-positive breast cancer, or paclitaxel in participants with advanced stage solid tumors.
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 & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 275
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Pathologically or histologically documented solid tumor.
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Locally advanced or relapsed/refractory disease or unresectable metastatic disease.
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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
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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
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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.
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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)
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Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
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Adequate hematological, hepatic, renal, and cardiac function
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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
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Any brain lesion requiring immediate local therapy
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Ongoing use of corticosteroids for central nervous system (CNS) symptoms at a dose of > 2 mg daily of dexamethasone (or equivalent)
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Leptomeningeal disease
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Uncontrolled seizures
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Participants for any chemotherapy cohort: ongoing Grade 2 or higher neuropathy of any cause
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Inability to swallow pills or any significant gastrointestinal disease that would preclude adequate oral absorption of medications.
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Ongoing adverse effects from prior treatment > CTCAE Grade 1 except for Grade 2 alopecia
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Corrected QT interval (QTc) of >470 milliseconds (ms) for females or >450 ms for males
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 2A: ELVN-002 + trastuzumab + CAPEOX dose escalation in colorectal cancer ELVN-002 ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Capecitabine will be administered orally twice daily at 1000 mg/m2 on days 1 - 14 of a 21-day cycle. Oxaliplatin will be administered intravenously at 130 mg/m2 on day 1 of a 21-day cycle. Part 2B: ELVN-002 + trastuzumab + mFOLFOX6 dose escalation in colorectal cancer ELVN-002 ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered intravenously at 6 mg/kg IV cycle 1, day 2 followed by 4 mg/kg IV cycle 1, day 15, and then one dose at 4mg/kg IV every 14 days. Fluorouracil (5-FU) will be administered intravenously as a 400 mg/m2 IV bolus on days 1 and 15 followed by 2400 mg/m2 over 46-48 hours of continuous infusion on days 1-3 and days 15-17 of a 28-day cycle. Leucovorin will be administered intravenously at 400 mg/m2 concurrently with oxaliplatin on days 1 and 15 of a 28-day cycle. Oxaliplatin will be administered intravenously at 85 mg/m2 IV on day 1 and 15 of a 28-day cycle. Part 2C: ELVN-002 + trastuzumab + capecitabine dose escalation in breast cancer ELVN-002 ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Capecitabine will be administered orally twice daily at 1000 mg/m2 on days 1 - 14 of a 21-day cycle. Part 2E: ELVN-002 + trastuzumab + eribulin dose escalation in breast cancer ELVN-002 ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Eribulin will be administered intravenously at 1.4 mg/m2 on days 1 and 8 of a 21-day cycle. Part 3C: ELVN-002 + trastuzumab dose expansion in other solid tumor type 1 ELVN-002 ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Part 3D: ELVN-002 + trastuzumab dose expansion in other solid tumor type 2 ELVN-002 ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Part 3E: ELVN-002 + trastuzumab dose expansion in other solid tumor type 3 ELVN-002 ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Part 4B: ELVN-002 + trastuzumab + mFOLFOX6 dose expansion in colorectal cancer ELVN-002 ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered intravenously at 6 mg/kg IV cycle 1, day 2 followed by 4 mg/kg IV cycle 1, day 15, and then one dose at 4mg/kg IV every 14 days. Fluorouracil (5-FU) will be administered intravenously as a 400 mg/m2 IV bolus on days 1 and 15 followed by 2400 mg/m2 over 46-48 hours of continuous infusion on days 1-3 and days 15-17 of a 28-day cycle. Leucovorin will be administered intravenously at 400 mg/m2 concurrently with oxaliplatin on days 1 and 15 of a 28-day cycle. Oxaliplatin will be administered intravenously at 85 mg/m2 IV on days 1 and 15 of a 28-day cycle. Part 1: ELVN-002 + trastuzumab dose escalation ELVN-002 ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Part 3B: ELVN-002 + trastuzumab dose expansion in breast cancer ELVN-002 ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Part 1: ELVN-002 + trastuzumab dose escalation Trastuzumab ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Part 2A: ELVN-002 + trastuzumab + CAPEOX dose escalation in colorectal cancer Trastuzumab ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Capecitabine will be administered orally twice daily at 1000 mg/m2 on days 1 - 14 of a 21-day cycle. Oxaliplatin will be administered intravenously at 130 mg/m2 on day 1 of a 21-day cycle. Part 2A: ELVN-002 + trastuzumab + CAPEOX dose escalation in colorectal cancer Oxaliplatin ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Capecitabine will be administered orally twice daily at 1000 mg/m2 on days 1 - 14 of a 21-day cycle. Oxaliplatin will be administered intravenously at 130 mg/m2 on day 1 of a 21-day cycle. Part 2A: ELVN-002 + trastuzumab + CAPEOX dose escalation in colorectal cancer Capecitabine ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Capecitabine will be administered orally twice daily at 1000 mg/m2 on days 1 - 14 of a 21-day cycle. Oxaliplatin will be administered intravenously at 130 mg/m2 on day 1 of a 21-day cycle. Part 2B: ELVN-002 + trastuzumab + mFOLFOX6 dose escalation in colorectal cancer Leucovorin ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered intravenously at 6 mg/kg IV cycle 1, day 2 followed by 4 mg/kg IV cycle 1, day 15, and then one dose at 4mg/kg IV every 14 days. Fluorouracil (5-FU) will be administered intravenously as a 400 mg/m2 IV bolus on days 1 and 15 followed by 2400 mg/m2 over 46-48 hours of continuous infusion on days 1-3 and days 15-17 of a 28-day cycle. Leucovorin will be administered intravenously at 400 mg/m2 concurrently with oxaliplatin on days 1 and 15 of a 28-day cycle. Oxaliplatin will be administered intravenously at 85 mg/m2 IV on day 1 and 15 of a 28-day cycle. Part 2B: ELVN-002 + trastuzumab + mFOLFOX6 dose escalation in colorectal cancer Trastuzumab ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered intravenously at 6 mg/kg IV cycle 1, day 2 followed by 4 mg/kg IV cycle 1, day 15, and then one dose at 4mg/kg IV every 14 days. Fluorouracil (5-FU) will be administered intravenously as a 400 mg/m2 IV bolus on days 1 and 15 followed by 2400 mg/m2 over 46-48 hours of continuous infusion on days 1-3 and days 15-17 of a 28-day cycle. Leucovorin will be administered intravenously at 400 mg/m2 concurrently with oxaliplatin on days 1 and 15 of a 28-day cycle. Oxaliplatin will be administered intravenously at 85 mg/m2 IV on day 1 and 15 of a 28-day cycle. Part 2B: ELVN-002 + trastuzumab + mFOLFOX6 dose escalation in colorectal cancer 5-Fluorouracil ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered intravenously at 6 mg/kg IV cycle 1, day 2 followed by 4 mg/kg IV cycle 1, day 15, and then one dose at 4mg/kg IV every 14 days. Fluorouracil (5-FU) will be administered intravenously as a 400 mg/m2 IV bolus on days 1 and 15 followed by 2400 mg/m2 over 46-48 hours of continuous infusion on days 1-3 and days 15-17 of a 28-day cycle. Leucovorin will be administered intravenously at 400 mg/m2 concurrently with oxaliplatin on days 1 and 15 of a 28-day cycle. Oxaliplatin will be administered intravenously at 85 mg/m2 IV on day 1 and 15 of a 28-day cycle. Part 2B: ELVN-002 + trastuzumab + mFOLFOX6 dose escalation in colorectal cancer Oxaliplatin ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered intravenously at 6 mg/kg IV cycle 1, day 2 followed by 4 mg/kg IV cycle 1, day 15, and then one dose at 4mg/kg IV every 14 days. Fluorouracil (5-FU) will be administered intravenously as a 400 mg/m2 IV bolus on days 1 and 15 followed by 2400 mg/m2 over 46-48 hours of continuous infusion on days 1-3 and days 15-17 of a 28-day cycle. Leucovorin will be administered intravenously at 400 mg/m2 concurrently with oxaliplatin on days 1 and 15 of a 28-day cycle. Oxaliplatin will be administered intravenously at 85 mg/m2 IV on day 1 and 15 of a 28-day cycle. Part 2C: ELVN-002 + trastuzumab + capecitabine dose escalation in breast cancer Trastuzumab ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Capecitabine will be administered orally twice daily at 1000 mg/m2 on days 1 - 14 of a 21-day cycle. Part 2C: ELVN-002 + trastuzumab + capecitabine dose escalation in breast cancer Capecitabine ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Capecitabine will be administered orally twice daily at 1000 mg/m2 on days 1 - 14 of a 21-day cycle. Part 2D: ELVN-002 + trastuzumab + paclitaxel dose escalation in solid tumors ELVN-002 ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Paclitaxel will be administered intravenously at 80 mg/m2 on days 1, 8, and 15 of a 21-day cycle. Part 2D: ELVN-002 + trastuzumab + paclitaxel dose escalation in solid tumors Trastuzumab ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Paclitaxel will be administered intravenously at 80 mg/m2 on days 1, 8, and 15 of a 21-day cycle. Part 2D: ELVN-002 + trastuzumab + paclitaxel dose escalation in solid tumors paclitaxel ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Paclitaxel will be administered intravenously at 80 mg/m2 on days 1, 8, and 15 of a 21-day cycle. Part 2E: ELVN-002 + trastuzumab + eribulin dose escalation in breast cancer Trastuzumab ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Eribulin will be administered intravenously at 1.4 mg/m2 on days 1 and 8 of a 21-day cycle. Part 2E: ELVN-002 + trastuzumab + eribulin dose escalation in breast cancer Eribulin ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Eribulin will be administered intravenously at 1.4 mg/m2 on days 1 and 8 of a 21-day cycle. Part 3A: ELVN-002 + trastuzumab dose expansion in colorectal cancer ELVN-002 ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+ Part 3A: ELVN-002 + trastuzumab dose expansion in colorectal cancer Trastuzumab ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+ Part 3B: ELVN-002 + trastuzumab dose expansion in breast cancer Trastuzumab ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Part 3C: ELVN-002 + trastuzumab dose expansion in other solid tumor type 1 Trastuzumab ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Part 3D: ELVN-002 + trastuzumab dose expansion in other solid tumor type 2 Trastuzumab ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Part 3E: ELVN-002 + trastuzumab dose expansion in other solid tumor type 3 Trastuzumab ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Part 4A: ELVN-002 + trastuzumab + CAPEOX dose expansion in colorectal cancer ELVN-002 ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Capecitabine will be administered orally twice daily at 1000 mg/m2 on Days 1 - 14 of a 21-day cycle. Oxaliplatin: will be administered intravenously at 130 mg/m2 on Day 1 of a 21-day cycle. Part 4A: ELVN-002 + trastuzumab + CAPEOX dose expansion in colorectal cancer Trastuzumab ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Capecitabine will be administered orally twice daily at 1000 mg/m2 on Days 1 - 14 of a 21-day cycle. Oxaliplatin: will be administered intravenously at 130 mg/m2 on Day 1 of a 21-day cycle. Part 4A: ELVN-002 + trastuzumab + CAPEOX dose expansion in colorectal cancer Oxaliplatin ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Capecitabine will be administered orally twice daily at 1000 mg/m2 on Days 1 - 14 of a 21-day cycle. Oxaliplatin: will be administered intravenously at 130 mg/m2 on Day 1 of a 21-day cycle. Part 4A: ELVN-002 + trastuzumab + CAPEOX dose expansion in colorectal cancer Capecitabine ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered IV (intravenously) in 21-day cycles, at 8mg/kg on cycle 1 day 2 followed by a dose of 6mg/kg on day 1 of cycles 2+. Capecitabine will be administered orally twice daily at 1000 mg/m2 on Days 1 - 14 of a 21-day cycle. Oxaliplatin: will be administered intravenously at 130 mg/m2 on Day 1 of a 21-day cycle. Part 4B: ELVN-002 + trastuzumab + mFOLFOX6 dose expansion in colorectal cancer Trastuzumab ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered intravenously at 6 mg/kg IV cycle 1, day 2 followed by 4 mg/kg IV cycle 1, day 15, and then one dose at 4mg/kg IV every 14 days. Fluorouracil (5-FU) will be administered intravenously as a 400 mg/m2 IV bolus on days 1 and 15 followed by 2400 mg/m2 over 46-48 hours of continuous infusion on days 1-3 and days 15-17 of a 28-day cycle. Leucovorin will be administered intravenously at 400 mg/m2 concurrently with oxaliplatin on days 1 and 15 of a 28-day cycle. Oxaliplatin will be administered intravenously at 85 mg/m2 IV on days 1 and 15 of a 28-day cycle. Part 4B: ELVN-002 + trastuzumab + mFOLFOX6 dose expansion in colorectal cancer 5-Fluorouracil ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered intravenously at 6 mg/kg IV cycle 1, day 2 followed by 4 mg/kg IV cycle 1, day 15, and then one dose at 4mg/kg IV every 14 days. Fluorouracil (5-FU) will be administered intravenously as a 400 mg/m2 IV bolus on days 1 and 15 followed by 2400 mg/m2 over 46-48 hours of continuous infusion on days 1-3 and days 15-17 of a 28-day cycle. Leucovorin will be administered intravenously at 400 mg/m2 concurrently with oxaliplatin on days 1 and 15 of a 28-day cycle. Oxaliplatin will be administered intravenously at 85 mg/m2 IV on days 1 and 15 of a 28-day cycle. Part 4B: ELVN-002 + trastuzumab + mFOLFOX6 dose expansion in colorectal cancer Oxaliplatin ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered intravenously at 6 mg/kg IV cycle 1, day 2 followed by 4 mg/kg IV cycle 1, day 15, and then one dose at 4mg/kg IV every 14 days. Fluorouracil (5-FU) will be administered intravenously as a 400 mg/m2 IV bolus on days 1 and 15 followed by 2400 mg/m2 over 46-48 hours of continuous infusion on days 1-3 and days 15-17 of a 28-day cycle. Leucovorin will be administered intravenously at 400 mg/m2 concurrently with oxaliplatin on days 1 and 15 of a 28-day cycle. Oxaliplatin will be administered intravenously at 85 mg/m2 IV on days 1 and 15 of a 28-day cycle. Part 4B: ELVN-002 + trastuzumab + mFOLFOX6 dose expansion in colorectal cancer Leucovorin ELVN-002 will be administered by mouth (orally) once or twice a day from cycle 1 day 1 onwards. Trastuzumab will be administered intravenously at 6 mg/kg IV cycle 1, day 2 followed by 4 mg/kg IV cycle 1, day 15, and then one dose at 4mg/kg IV every 14 days. Fluorouracil (5-FU) will be administered intravenously as a 400 mg/m2 IV bolus on days 1 and 15 followed by 2400 mg/m2 over 46-48 hours of continuous infusion on days 1-3 and days 15-17 of a 28-day cycle. Leucovorin will be administered intravenously at 400 mg/m2 concurrently with oxaliplatin on days 1 and 15 of a 28-day cycle. Oxaliplatin will be administered intravenously at 85 mg/m2 IV on days 1 and 15 of a 28-day cycle.
- Primary Outcome Measures
Name Time Method 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 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 electrocardiogram abnormalities 24 months Clinically significant electrocardiogram abnormalities will be used to support that the recommended doses for expansion are likely to be tolerable
- Secondary Outcome Measures
Name Time Method Brain metastases response (Phase 1b only) 24 months For patients with measurable brain metastases at baseline, the percent of patients who have a confirmed response per RECIST v1.1
PK parameter of maximum concentration of ELVN-002 (Phase 1a only) 24 months The maximum concentration of ELVN-002 measured in the blood at any time point at steady state
PK parameter of area under the curve of ELVN-002 (Phase 1a only) 24 months The concentration of ELVN-002 measured in the blood over 24 hours at steady state
PK parameter of terminal half life of ELVN-002 (Phase 1a only) 24 months The half life of ELVN-002 calculated from the concentration of ELVN-002 measured in blood
Confirmed objective response rate (ORR) 24 months For patients with measurable disease at baseline, confirmed response as assessed by investigator per RECIST v1.1
Duration of response (DOR; Phase 1b only) 24 months The time from the first response to progression or death per RECIST v1.1
PK parameter of minimum concentration of ELVN-002 (Phase 1a only) 24 months The minimum concentration of ELVN-002 measured in the blood at any time point at steady
Trial Locations
- Locations (31)
Azienda Ospedaliero-Universitaria Renato Dulbecco
🇮🇹Catanzaro, Italy
BRCR Medical Center Inc.
🇺🇸Plantation, Florida, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
NEXT Virginia
🇺🇸Fairfax, Virginia, United States
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
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
CHA Bundang Medical Center
🇰🇷Seongnam-si, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Soeul, Korea, Republic of
The Catholic University of Korea, St. Vincent's Hospital
🇰🇷Suwon, Korea, Republic of
Radboud UMC
🇳🇱Nijmegen, Netherlands
NEXT Oncology-Hospital Quironsalud Barcelona
🇪🇸Barcelona, Spain
START Barcelona_HM Nou Delfos
🇪🇸Barcelona, Spain
Hospital Universitari Dexeus - Grupo Quironsalud
🇪🇸Barcelona, Spain
Hospital Beata Maria Ana
🇪🇸Madrid, Spain
Clinica universitaria Navarra - Madrid
🇪🇸Madrid, Spain
Instituto de Investigacion Oncologica Vall d'Hebron (VHIO) - EPON
🇪🇸Barcelona, Spain
START Madrid - Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Clinica univeritaria Navarra - Pamplonas
🇪🇸Pamplona, Spain
Fundacion Instituto Valenciano de Oncologia
🇪🇸Valencia, Spain