ELVN-002 + Trastuzumab for HER2+ Colorectal and Breast Cancer
Recruiting in Palo Alto (17 mi)
+30 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Enliven Therapeutics
Must be taking: Trastuzumab
Must not be taking: Corticosteroids, Chemotherapy
Disqualifiers: Brain lesions, Leptomeningeal disease, Seizures, others
No Placebo Group
Trial Summary
What is the purpose of this trial?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.
Do I need to stop my current medications to join the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, there are specific timeframes for stopping certain treatments before starting the trial, such as chemotherapy, immunotherapy, and hormonal therapy. It's best to discuss your current medications with the trial team to get personalized advice.
What data supports the effectiveness of this drug combination for HER2-positive colorectal and breast cancer?
Research shows that combining trastuzumab with other HER2-targeted drugs like lapatinib can be effective in treating HER2-positive cancers. In a study, 30% of patients with HER2-positive colorectal cancer responded to a similar dual HER2 blockade, suggesting potential benefits for this drug combination.
12345Is the combination of ELVN-002 and Trastuzumab safe for humans?
Trastuzumab, used in combination with other treatments, has been shown to have a generally favorable safety profile, though it can increase the risk of cardiac issues like heart failure in some patients. The safety of ELVN-002 specifically is not detailed in the provided research, but trastuzumab's safety in breast cancer treatment is well-documented.
678910How is the drug ELVN-002 + Trastuzumab different from other treatments for HER2-positive colorectal and breast cancer?
ELVN-002 combined with Trastuzumab is unique because it targets HER2-positive cancers, which are often resistant to standard treatments. This combination may offer a new option for patients who do not respond to existing therapies like EGFR inhibitors.
13111213Eligibility Criteria
This trial is for people with advanced-stage tumors that are HER2-positive, including those with breast or colorectal cancer. Participants should be able to receive the drug ELVN-002 along with trastuzumab and possibly chemotherapy.Inclusion Criteria
My cancer is HER2-positive according to tests.
My previous cancer treatments vary based on the trial phase and my cancer type.
I am fully active or can carry out light work.
+4 more
Exclusion Criteria
My cancer has spread to the lining of my brain and spinal cord.
I haven't had cancer treatment within the specified time before starting this trial.
I am taking more than 2 mg of dexamethasone daily for brain-related symptoms.
+6 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive ELVN-002 in combination with trastuzumab, with or without chemotherapy, in 21-day cycles
24 months
Multiple visits per cycle (in-person)
Follow-up
Participants are monitored for safety, tolerability, and efficacy after treatment
24 months
Participant Groups
The study is testing the safety and proper dosage of a new treatment, ELVN-002, when used with trastuzumab alone or in combination with various chemotherapies (like 5-Fluorouracil, Oxaliplatin) in patients with HER2-positive cancers.
13Treatment groups
Experimental Treatment
Group I: Part 4B: ELVN-002 + trastuzumab + mFOLFOX6 dose expansion in colorectal cancerExperimental Treatment5 Interventions
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.
Group II: Part 4A: ELVN-002 + trastuzumab + CAPEOX dose expansion in colorectal cancerExperimental Treatment4 Interventions
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.
Group III: Part 3E: ELVN-002 + trastuzumab dose expansion in other solid tumor type 3Experimental Treatment2 Interventions
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+.
Group IV: Part 3D: ELVN-002 + trastuzumab dose expansion in other solid tumor type 2Experimental Treatment2 Interventions
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+.
Group V: Part 3C: ELVN-002 + trastuzumab dose expansion in other solid tumor type 1Experimental Treatment2 Interventions
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+.
Group VI: Part 3B: ELVN-002 + trastuzumab dose expansion in breast cancerExperimental Treatment2 Interventions
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+.
Group VII: Part 3A: ELVN-002 + trastuzumab dose expansion in colorectal cancerExperimental Treatment2 Interventions
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+
Group VIII: Part 2E: ELVN-002 + trastuzumab + eribulin dose escalation in breast cancerExperimental Treatment3 Interventions
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.
Group IX: Part 2D: ELVN-002 + trastuzumab + paclitaxel dose escalation in solid tumorsExperimental Treatment3 Interventions
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.
Group X: Part 2C: ELVN-002 + trastuzumab + capecitabine dose escalation in breast cancerExperimental Treatment3 Interventions
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.
Group XI: Part 2B: ELVN-002 + trastuzumab + mFOLFOX6 dose escalation in colorectal cancerExperimental Treatment5 Interventions
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.
Group XII: Part 2A: ELVN-002 + trastuzumab + CAPEOX dose escalation in colorectal cancerExperimental Treatment4 Interventions
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.
Group XIII: Part 1: ELVN-002 + trastuzumab dose escalationExperimental Treatment2 Interventions
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+.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Washington UniversitySaint Louis, MO
BRCR Medical Center Inc.Plantation, FL
NEXT VirginiaFairfax, VA
Loading ...
Who Is Running the Clinical Trial?
Enliven TherapeuticsLead Sponsor
References
Colorectal Cancer Yields to Dual HER2 Blockade. [2018]According to data from a phase II study, the anti-HER2 combination of trastuzumab and lapatinib is active in patients with KRAS-wild-type, HER2-positive metastatic colorectal cancer. None of the study participants responded to previous, standard treatment with the EGFR inhibitors cetuximab or panitumumab, but 30% achieved an objective response to dual HER2 blockade.
Emerging strategies for the dual inhibition of HER2-positive breast cancer. [2019]To review the recently published trials to help us refine and optimize the use of approved HER2-targeted agents (trastuzumab and lapatinib) and highlight future combination strategies for the treatment of HER2-positive breast cancer.
[Lapatinib plus transtuzumab for HER-2 positiva metastatic breast cancer: experience of use]. [2018]To describe the outcomes produced by concomitant use of HER2-receptor inhibitors Lapatinib and Trastuzumab for the treatment of HER 2-positive metastatic breast cancer.
Adjuvant/neoadjuvant trastuzumab therapy in women with HER-2/neu-overexpressing breast cancer: a systematic review. [2018]A systematic review was undertaken to evaluate the evidence for the use of trastuzumab as (neo)adjuvant therapy for women with HER-2/neu-positive breast cancer and to develop and support recommendations pertaining to its use across five domains: as a single-agent therapy, in combination with chemotherapy, methods to identify women who will benefit from it, adverse events associated with it, and optimal dose, schedule, and duration.
Randomized phase II trial of gemcitabine-cisplatin with or without trastuzumab in HER2-positive non-small-cell lung cancer. [2022]Trastuzumab provides significant clinical benefits in HER2-positive metastatic breast cancer patients when administered in combination with chemotherapy. Chemotherapy has also been shown to be beneficial in some patients with advanced non-small-cell lung cancer (NSCLC). The present randomized phase II trial examined the effect of adding trastuzumab to a standard chemotherapeutic combination (gemcitabine-cisplatin) in patients with HER2-positive NSCLC.
Cardiac toxicity in breast cancer patients treated with dual HER2 blockade. [2018]Although dual HER2 blockade shows promising results in patients with HER2-positive breast cancer it is unclear whether this treatment strategy increases the risk for cardiac adverse events. We conducted a meta-analysis of randomized trials to investigate the risk of cardiac adverse events when a combination of anti-HER2 therapies compared to anti-HER2 monotherapy. We searched Medline, the Cochrane library, as well as the electronic abstract databases of the major international congresses' proceedings to identify randomized trials that evaluated the administration of anti-HER2 monotherapy (lapatinib or trastuzumab or pertuzumab) versus anti-HER2 combination (pertuzumab plus trastuzumab or trastuzumab plus lapatinib) therapy in breast cancer. The trials were considered eligible if the only systematic difference between the study arms was the type of anti-HER2 therapy used. Study outcomes were the congestive heart failure (CHF) grade ≥3 and left ventricular ejection fraction (LVEF) decline
Does dual HER-2 blockade treatment increase the risk of severe toxicities of special interests in breast cancer patients: A meta-analysis of randomized controlled trials. [2018]Although dual HER-2 blockade treatment could offer greater clinical efficacy in breast cancer, the risk of severe toxicities of special interest related to this combined regimen in breast cancer remained unknown. We systematically searched public databases (MEDLINE, EMBASE, Cochrane library) to identify relevant studies that comparing anti-HER2 monotherapy (lapatinib or trastuzumab or pertuzumab) with dual HER-2 blockade treatment (pertuzumab plus trastuzumab or trastuzumab plus lapatinib) in breast cancer. A total of 11,941 breast cancer patients from 9 trials were included for analysis. Meta-analysis showed that dual HER2 blockade treatment significantly increased the risk of severe diarrhea (OR 2.52, p
Adjuvant trastuzumab for HER2-positive early breast cancer. [2015]This article reviews clinical data on adjuvant trastuzumab (Herceptin, Genentech, Inc.) for patients with HER2-positive early breast cancer. Published articles were searched via PubMed (1985-2009), and abstracts were located from meeting books or search engines of congress Web sites (1994-2009). Search terms included breast neoplasms, breast cancer, breast tumor, or breast tumour and adjuvant plus HER2-positive plus trastuzumab. Trastuzumab improves clinical outcomes as well as disease-free and overall survival for patients with early HER2-positive breast cancer compared with adjuvant chemotherapy alone in this population. Trastuzumab has a favorable safety profile; levels of cardiac dysfunction were acceptable in all adjuvant trials, and cardiac dysfunction was manageable in most cases. Awareness of the clinical data will help nurses identify patients eligible for adjuvant trastuzumab, familiarize them with treatment and cardiac monitoring plans, and provide them with information to help advise, treat, and support patients from diagnosis through completion of therapy.
FDA Approval Summary: Ado-Trastuzumab Emtansine for the Adjuvant Treatment of HER2-positive Early Breast Cancer. [2021]On May 3, 2019, the FDA granted regular approval to ado-trastuzumab emtansine (KADCYLA), for the adjuvant treatment of patients with HER2-positive early-breast cancer (EBC) who have residual invasive disease after neoadjuvant taxane-based chemotherapy and trastuzumab-based treatment. Approval was based on data from the KATHERINE trial, which randomized patients to receive ado-trastuzumab emtansine or trastuzumab. At 3 years, the event-free rate for invasive disease-free survival in the ado-trastuzumab emtansine arm was 88.3% [95% confidence interval (CI), 85.8-90.7] compared with 77.0% (95% CI, 73.8-80.7) in the trastuzumab arm, (HR, 0.50; 95% CI, 0.39-0.64; P < 0.0001). Results from secondary endpoints, subgroup analyses, and sensitivity analyses generally supported the primary efficacy endpoint results. Common adverse reactions (>25% and higher incidence in ado-trastuzumab emtansine arm) with ado-trastuzumab emtansine were fatigue, nausea, increased transaminases, musculoskeletal pain, hemorrhage, thrombocytopenia, headache, peripheral neuropathy, and arthralgia. Ado-trastuzumab emtansine is the first drug approved for the treatment of patients with residual disease after neoadjuvant treatment and surgery. This article summarizes the FDA review and the data supporting the approval of ado-trastuzumab emtansine as a component of treatment for patients with HER2-positive EBC with residual disease.
Adjuvant trastuzumab therapy for HER2-positive breast cancer. [2022]HER2 is overexpressed or gene amplified in 20%-25% of breast cancers. The anti-HER2 monoclonal antibody trastuzumab targets HER2-positive tumors, inhibiting proliferation and inducing cell death via extracellular and intracellular mechanisms. The clinical benefits observed with trastuzumab in the metastatic setting provided the rationale for assessing trastuzumab in the treatment of early breast cancer. Four large phase III adjuvant trials (NSABP B-31, NCCTG N9831, HERA, and BCIRG 006) investigated the efficacy and safety of 1 or 2 years of trastuzumab given in combination with or after standard adjuvant chemotherapy. The addition of 1 year of trastuzumab to adjuvant chemotherapy significantly improved disease-free survival (DFS) by 33%-52% and overall survival by 34%-41% in the 4 trials. The DFS benefits were observed regardless of age, nodal status, hormonal status, or tumor size in all trials. The cumulative incidence of congestive heart failure or cardiac death ranged from 0-0.9% in the control arms and 0-3.8% in the trastuzumab-containing arms. These were below the safety cutoff points set by the individual studies' independent data monitoring committees, indicating acceptable cardiac safety. Risk factors associated with cardiac dysfunction included baseline left ventricular ejection fraction level, hypertension, and older age. The addition of trastuzumab to adjuvant chemotherapy provides significant survival benefits with a positive benefit/risk ratio. Ongoing and planned trials correlated with basic science will enhance our understanding of HER2-positive disease, leading to treatment optimization and further improvements in patient outcomes.
Trastuzumab Combined with Irinotecan in Patients with HER2-Positive Metastatic Colorectal Cancer: A Phase II Single-Arm Study and Exploratory Biomarker Analysis. [2023]The human epidermal growth factor receptor 2 (HER2) is an established therapeutic target for various kinds of solid tumors. HER2 amplification occurs in approximately 1% to 6% of colorectal cancer. In this study, we aimed to assess the efficacy and safety of trastuzumab in combination with chemotherapy in HER2-positive metastatic colorectal cancer (mCRC).
A review of the use of trastuzumab (Herceptin) plus vinorelbine in metastatic breast cancer. [2020]The combination of trastuzumab (Herceptin) and vinorelbine (Navelbine) in the treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) is valuable for several reasons. There is proven synergism of these agents in preclinical models, both agents are well tolerated and there is minimal overlapping toxicity. This article reviews clinical experience with trastuzumab and vinorelbine from phase II/III trials including >450 assessable patients. Results across the trials show objective response rates for the combination in the range of 44%-86% (51%-86% as first-line treatment) and a median duration of response of 10-17.5 months. Approximately 50% of patients experience grade 3/4 neutropenia, which is of short duration and manageable. Symptomatic cardiac events are infrequent (seven episodes of grade 3 toxicity across all trials). Overall, trastuzumab-vinorelbine combination therapy offers patients with HER2-positive MBC, an effective and well-tolerated treatment that is suitable for prolonged duration of use.
Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial. [2022]We previously found that dual HER2 blockade with trastuzumab and lapatinib led to inhibition of tumour growth in patient-derived xenografts of HER2-amplified metastatic colorectal cancer. In this study, we aimed to assess the antitumour activity of trastuzumab and lapatinib in patients with HER2-positive colorectal cancer.