ELVN-002 for Non-Small Cell Lung Cancer

(HER2 Trial)

Not currently recruiting at 50 trial locations

Overseen By Sabine Tricon

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Enliven Therapeutics

Disqualifiers: Severe cardiac arrhythmias, Active malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ELVN-002 for certain cancers with an abnormal HER2 gene, focusing on non-small cell lung cancer. Researchers aim to determine if ELVN-002 is safe and how it behaves in the body at different doses. They also seek to assess its potential to shrink tumors. Suitable participants have non-small cell lung cancer with a HER2 mutation and have tried other treatments without success. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that ELVN-002 is likely to be safe for humans?

Research has shown that ELVN-002 has potential in early studies for people with cancers linked to an abnormal HER2 gene. Early data suggest it absorbs and distributes well in the body. Importantly, the risk of a serious heart-related side effect called QTc prolongation is low.

Since this trial is in its early phase, the main goal is to test the safety and tolerability of ELVN-002 at different doses. Researchers closely monitor how people react to the treatment. In these initial tests, ELVN-002 has effectively targeted common HER2 mutations.

When combined with other treatments like T-DM1 and T-DXd, researchers are also assessing the safety of these combinations and their potential to improve treatment effectiveness.

As this is the first time ELVN-002 is being tested in humans, extensive safety data is not yet available. However, early results are promising and suggest that ELVN-002 could be well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ELVN-002 for non-small cell lung cancer because it offers a unique approach compared to current treatments. Unlike traditional therapies, which often involve intravenous chemotherapy, ELVN-002 is an oral capsule, potentially providing more convenience and ease for patients. Additionally, ELVN-002 is being studied both on its own and in combination with other drugs like T-DM1 and T-DXd, which might enhance its effectiveness. This exploration of different dosing strategies and combinations could lead to improved outcomes for patients who haven't responded well to existing treatment options.

What evidence suggests that ELVN-002 could be an effective treatment for non-small cell lung cancer?

Research shows that ELVN-002 may help treat non-small cell lung cancer, particularly when specific genetic changes, known as HER2 abnormalities, are present. Early lab studies found that ELVN-002 shrank tumors at all tested doses. In this trial, some participants will receive ELVN-002 alone, while others will receive it with treatments like T-DM1 or T-DXd. These combinations have shown even more promise in fighting tumors. Another similar drug, Nivolumab, has effectively boosted the immune system to combat this type of lung cancer. These findings suggest that ELVN-002 could be effective, but more research is needed to confirm these results in people. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• ELVN-002

Trial Overview 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.

How Is the Trial Designed?

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.

Who Is Running the Clinical Trial?

Enliven Therapeutics

Lead Sponsor

Trials

4

Recruited

670+

Published Research Related to This Trial

In a study of 1064 patients with left-sided non-small cell lung cancer (NSCLC), those who underwent 4L node dissection (4LND) had significantly better disease-free survival (DFS) and overall survival (OS) compared to those who did not, with 5-year DFS rates of 52.6% versus 46.7% and OS rates of 65.8% versus 56.3%.

The benefits of 4LND were particularly pronounced in patients with stage II and advanced stage disease, suggesting that 4LND should be considered a standard procedure for these patients to improve their survival outcomes.

NCBI (Pubmed)

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. Zhao, K., Wei, S., Mei, J., et al.[2019]

The study found that the number of positive lymph nodes (nPLN) and the positive lymph node rate (LNR) are better indicators of overall survival in non-small cell lung cancer (NSCLC) than the traditional N-stage classification, based on statistical analysis of patient data.

Both nPLN and LNR classifications showed improved prognostic performance, with higher C-index values and lower AIC and BIC scores, suggesting they could enhance the accuracy of survival predictions for patients with lymph node-positive NSCLC.

NCBI (Pubmed)

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. Guo, Q., Hu, S., Wang, S., et al.[2023]

In a study of 69 patients with advanced non-small cell lung cancer, higher nivolumab clearance rates at the first dose were associated with a significantly increased risk of death, indicating that nivolumab clearance can be a prognostic indicator for survival.

The study found that while nivolumab clearance showed high sensitivity as a biomarker for predicting outcomes, its specificity was low, suggesting that while it can identify patients at risk, it may not effectively distinguish between responders and non-responders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic Value of Nivolumab Clearance in Non-Small Cell Lung Cancer Patients for Survival Early in Treatment. Otten, LS., Piet, B., van den Haak, D., et al.[2023]

In a study of 74 patients with metastatic non-small cell lung cancer (NSCLC) enrolled in early phase immunotherapy trials, those who had not previously received immunotherapy had a median overall survival (mOS) of 8.2 months, while those who had progressed on prior immunotherapy had a slightly better mOS of 10.5 months, indicating that prior treatment may not significantly hinder subsequent immunotherapy effectiveness.

Prognostic scores, particularly the Royal Marsden Hospital (RMH) score and the MD Anderson Cancer Center (MDACC) score, were effective in predicting overall survival, with a high ANC/ALC ratio (NLR) indicating poorer outcomes, suggesting that these scores can help identify patients who may not benefit from early phase immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicting outcomes in patients with advanced non-small cell lung cancer enrolled in early phase immunotherapy trials. Maymani, H., Hess, K., Groisberg, R., et al.[2022]

Nivolumab, a PD-1 receptor inhibitor, shows an objective response rate of 18% and a 1-year overall survival rate of 45% in patients with advanced non-small-cell lung cancer, based on a meta-analysis of 20 studies involving 3404 patients.

The presence of PD-L1 expression in patients is associated with a better response to nivolumab, indicating that PD-L1 status can help predict treatment outcomes.

NCBI (Pubmed)

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. Zhao, B., Zhang, W., Yu, D., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05650879

ELVN-002 in HER2 Mutant Non-Small Cell Lung Cancer The goal of this clinical trial is to test ELVN-002 in people with cancers that have an abnormal HER2 gene.

2. withpower.com withpower.com/trial/phase-1-her2-amplification-2-2023-e1da3

ELVN-002 for Non-Small Cell Lung Cancer (HER2 Trial) 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11171190/

HER2-Altered Non-Small Cell Lung Cancer - PubMed Central Non-selective HER2-TKIs demonstrated limited efficacy in treating patients with HER2-altered NSCLC, prompting the development of next-generation ...

4. enliventherapeutics.com enliventherapeutics.com/file.cfm/39/docs/enliven_aacr_april_orlando_poster_digital_2023.pdf

Preclinical Activity of ELVN-002 ELVN-002 yielded tumor regressions at all doses tested. · Poziotinib's maximum tolerated dose in this model was 1 mg/kg, and this dose yielded an exposure ...

5. trialx.com trialx.com/clinical-trials/listings/268710/elvn-002-in-her2-mutant-non-small-cell-lung-cancer/

ELVN-002 in HER2 Mutant Non-Small Cell Lung Cancer The third main question is to see if ELVN-002 works to shrink cancers that have HER2 genetic abnormalities, particularly non-small cell lung cancer. Description.

6. sciencedirect.com sciencedirect.com/science/article/pii/S1556086423014028

Phase 1a/b study of ELVN-002, in Solid Tumors with HER2 ... ELVN-002-001 is a first-in-human study to evaluate the safety, tolerability, PK and preliminary anti-tumor activity of ELVN-002 in solid tumors with HER2 ...

7. jto.org jto.org/article/S1556-0864(23)01403-X/pdf

P2.09-28 Effect of TP53 Variants in HER2-mutated Non- ... The trial will also evaluate the safety of the combination of ELVN-002 with T-DXd in HER2-mutant. NSCLC and with T-DM1 in HER2-positive breast cancer.