ELVN-002 for Non-Small Cell Lung Cancer

(HER2 Trial)

Recruiting in Palo Alto (17 mi)

+39 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Enliven Therapeutics

Disqualifiers: Severe cardiac arrhythmias, Active malignancy, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests ELVN-002, a new drug, in people with cancers that have an abnormal HER2 gene. It aims to see if the drug is safe and can shrink these tumors, especially in advanced stage solid tumors and non-small cell lung cancer.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it does mention that you should not have taken certain HER2 tyrosine kinase inhibitors before joining the trial.

What data supports the effectiveness of the drug ELVN-002 for non-small cell lung cancer?

Nivolumab, a drug similar to ELVN-002, has shown some effectiveness in treating non-small cell lung cancer by enhancing the immune system's ability to fight cancer, with an objective response rate of 18% and a 1-year overall survival rate of 45% in patients.

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Eligibility Criteria

This trial is for adults with advanced solid tumors, particularly non-small cell lung cancer (NSCLC), that have HER2 mutations and have progressed after standard treatments or are unsuitable for them. Participants must be in good physical condition with proper heart function and adequate blood counts. Those with brain lesions needing immediate treatment, active infections, uncontrolled seizures, certain heart conditions, or another active cancer within the last 2 years cannot join.

Inclusion Criteria

You should have good overall health, normal heart function, and specific levels of blood cells, liver function, and kidney function.

My advanced NSCLC has worsened after treatment and has a HER2 mutation but no EGFR, ROS1, ALK, or BRAF V600E mutations.

My advanced cancer has not responded to standard treatments and is HER2 positive.

Exclusion Criteria

I have ongoing liver problems.

I haven't had any cancer except for basal cell skin cancer or in situ carcinoma in the last 2 years.

My cancer has spread to the lining of my brain and spinal cord.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Part 1 involves dose escalation with ELVN-002 monotherapy for patients with advanced stage solid tumors with HER2 mutation, amplification, or high HER2 over-expression.

Until disease progression or discontinuation

Dose Exploration

Part 2 involves dose exploration where additional patients may be enrolled at dose levels that have cleared the dose escalation to further evaluate safety, tolerability, pharmacokinetics, and clinical activity.

Until disease progression or discontinuation

Dose Expansion

Part 3 is a dose expansion of ELVN-002 monotherapy enrolling up to 40 patients with advanced stage HER2 mutant non-small cell lung cancer.

Until disease progression or discontinuation

Combination Dose Escalation

Part 4 involves combination dose escalation with ELVN-002 and either fam-trastuzumab deruxtecan-nxki or trastuzumab emtansine, based on results from Parts 1 and 2.

Until disease progression or discontinuation

Follow-up

Participants are monitored for safety and effectiveness after treatment.

24 months

Participant Groups

The trial is testing ELVN-002's safety at various doses in patients with HER2 gene abnormalities. It will also measure how much of the drug stays in the blood over time and whether it effectively shrinks tumors. Some participants will receive ELVN-002 alone while others may get it alongside other drugs like Fam-Trastuzumab Deruxtecan-Nxki depending on their specific type of cancer.

Group I: Phase 1b Monotherapy Dose Expansion Experimental Treatment 1 Intervention

ELVN-002 will be administered either once or twice daily. A maximum of 40 patients will enroll in this arm. Patients will be randomized 1:1 to one of two dose levels. ELVN-002 is an oral capsule. Duration of treatment will be until disease progression or patient discontinues ELVN-002 for another reason.

Group II: Phase 1a Monotherapy Dose Exploration Experimental Treatment 1 Intervention

ELVN-002 will be administered either once or twice daily. A maximum of 80 patients will enroll in this arm. A maximum of 10 patients may be enrolled at a single dose or tumor type. ELVN-002 is an oral capsule. Duration of treatment will be until disease progression or patient discontinues ELVN-002 for another reason.

Group III: Phase 1a Monotherapy Dose Escalation Experimental Treatment 1 Intervention

ELVN-002 will be administered either once or twice daily. Each cohort of patients will receive a higher dose. ELVN-002 is an oral capsule. Duration of treatment will be until disease progression or patient discontinues ELVN-002 for another reason.

Group IV: Phase 1a Combination Dose Escalation with T-DXd Experimental Treatment 2 Interventions

ELVN-002 will be administered either once or twice daily starting on Day 1. ELVN-002 is an oral capsule. Each cohort will receive a higher dose of ELVN-002. All patients in all cohorts will initiate with 5.4mg/kg of intravenous T-DXd once every 3 weeks starting on day 22 of the study. Duration of treatment will be until disease progression or patient discontinues ELVN-002 for another reason.

Group V: Phase 1a Combination Dose Escalation with T-DM1 Experimental Treatment 2 Interventions

ELVN-002 will be administered either once or twice daily starting on Day 1. ELVN-002 is an oral capsule. Each cohort will receive a higher dose of ELVN-002. All patients in all cohorts will initiate with 3.6 mg/kg of intravenous T-DM1 once every 3 weeks starting on day 22 of the study. Duration of treatment will be until disease progression or patient discontinues ELVN-002 for another reason.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

NEXT/Virginia Cancer Specialists Fairfax, VA

Dana Farber Cancer Institute Boston, MA

University of Colorado - Anschutz Medical Campus - PPDS Aurora, CO

BRCR Medical Center Inc Plantation, FL

More Trial Locations

Who Is Running the Clinical Trial?

Enliven Therapeutics Lead Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

Survival Benefit of Left Lower Paratracheal (4L) Lymph Node Dissection for Patients with Left-Sided Non-small Cell Lung Cancer: Once Neglected But of Great Importance. [2019] The aim of this study was to compare survival outcomes between non-small cell lung cancer (NSCLC) patients with or without 4L node dissection (4LND) and to evaluate the potential patient population who will particularly benefit from 4LND.

2. Switzerland pubmed.ncbi.nlm.nih.gov

Prognostic Value of Nivolumab Clearance in Non-Small Cell Lung Cancer Patients for Survival Early in Treatment. [2023] Immune checkpoint inhibitors improved survival of advanced stage non-small cell lung cancer patients, but the overall response rate remains low. A biomarker that identifies non-responders would be helpful to allow treatment decisions. Clearance of immune checkpoint inhibitors is related to treatment response, but its prognostic potential early in treatment remains unknown. Our primary aim was to investigate the prognostic potential of nivolumab clearance for overall survival early in treatment. Our secondary aim was to evaluate the performance of nivolumab clearance as prognostic biomarker.

3. Ireland pubmed.ncbi.nlm.nih.gov

Predicting outcomes in patients with advanced non-small cell lung cancer enrolled in early phase immunotherapy trials. [2022] Immunotherapy (IO) has altered the non-small cell lung cancer (NSCLC) therapeutic landscape. However, the majority of patients do not respond to immune-checkpoint blockade, and subsequently either receive further chemotherapy or are referred for clinical trials. Here we examined the outcomes and predictors of response to IO in early phase clinical trials.

4. United States pubmed.ncbi.nlm.nih.gov

The benefit and risk of nivolumab in non-small-cell lung cancer: a single-arm meta-analysis of noncomparative clinical studies and randomized controlled trials. [2019] Nivolumab is a programmed cell death 1 (PD-1) receptor inhibitor antibody that enhances immune system antitumor activity. Although it is used for treating advanced non-small-cell lung cancer (NSCLC), its actual efficacy has not been determined. We searched PubMed, the Cochrane Library, Embase, MEDLINE, and Web of Science for related noncomparative clinical studies and randomized controlled trials (RCTs) to assess nivolumab benefit and risk in NSCLC. The main outcomes were objective response rate (ORR), 1-year overall survival rate (1-yOS rate), and progression-free survival rate at 24 weeks (PFS at 24 weeks rate), any-grade adverse effects rate (any-grade AEs%), and grade 3-4 AE rate (grade 3-4 AEs%). Relative risk (RR) was used to compare ORR in patients with positive and negative programmed cell death ligand 1 (PD-L1) expression. Random-effects models were used to determine pooled effect size and two-sided 95% confidence intervals (95% CI). We included 20 studies (17 noncomparative open-label cohort studies, three RCTs) involving 3404 patients in our meta-analysis. The modified nivolumab ORR was 18% (95% CI: 15-20%), the 1-yOS rate was 45% (95% CI: 40-50%), PFS at 24 weeks rate was 42% (95% CI: 37-48%), any-grade AEs% was 61% (95% CI: 50-73%), and grade 3-4 AEs% was 12% (95% CI: 9-16%). PD-L1 expression was related with the nivolumab ORR. Nivolumab potentially causes ongoing response, long-term PFS, and reduced treatment-related AEs. PD-L1 expression predicts the outcome of nivolumab immunotherapy. More high-quality and well-designed RCTs with large sample sizes are warranted to prove our findings.

5. England pubmed.ncbi.nlm.nih.gov

Comparative analysis of methodologies for predicting overall survival in patients with non-small cell lung cancer based on the number and rate of resected positive lymph nodes: A study based on the SEER database for 2010 through 2019. [2023] Lymph node (LN) metastasis is crucial in non-small cell lung cancer (NSCLC) prognosis and treatment, but the TNM system lacks LN quantity consideration. Our goal is to investigate the role of positive LNs (nPLN) and positive LN rate (LNR) in overall survival (OS) and assess whether they offer higher value in prognostic assessment of NSCLC than N-stage.