Zenocutuzumab for Non-Small Cell Lung and Prostate Cancers

No longer recruiting at 7 trial locations

Overseen By Shekeab Jauhari, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merus N.V.

Must be taking: AR signaling inhibitors

Must not be taking: Anti-HER3 therapies, Afatinib

Disqualifiers: CNS metastases, Uncontrolled hypertension, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 9 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of zenocutuzumab for certain lung and prostate cancers. It includes two groups: one with non-small cell lung cancer (NSCLC) featuring a specific gene fusion called NRG1, and the other with metastatic castration-resistant prostate cancer (mCRPC). Participants will receive zenocutuzumab, sometimes combined with other cancer medications, to determine its potential in controlling their cancer. Eligible participants are those with the specified lung or prostate cancer who have not responded to standard treatments. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are in Group B, you must continue ongoing therapy with a next-generation AR signaling inhibitor like enzalutamide or abiraterone, which should have been started at least 90 days before screening.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that zenocutuzumab is generally well-tolerated, particularly in patients with advanced non-small cell lung cancer (NSCLC). One study found this treatment effective and safe for patients. The FDA granted it accelerated approval for NSCLC, indicating confidence in its safety.

For those considering this treatment for metastatic castration-resistant prostate cancer (mCRPC), the safety of zenocutuzumab remains under investigation. Ongoing research continues to explore its safety across various cancer types, enhancing understanding of its effects.

In summary, while research on zenocutuzumab continues, existing studies and FDA approval for NSCLC suggest it is well-tolerated. Prospective trial participants should consult a healthcare provider about personal risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for lung and prostate cancers?

Zenocutuzumab is unique because it targets the NRG1 gene fusions found in certain cancers, which is different from most existing treatments for non-small cell lung cancer (NSCLC) and metastatic castration-resistant prostate cancer (mCRPC) that often focus on general cancer cell growth or androgen receptors. Unlike traditional therapies, zenocutuzumab is a bispecific antibody that simultaneously engages two targets, potentially improving efficacy. Researchers are excited because this novel mechanism of action could lead to more effective treatments with fewer side effects for patients who have limited options after standard therapies like chemotherapy or androgen receptor inhibitors.

What evidence suggests that this trial's treatments could be effective for non-small cell lung and prostate cancers?

Research has shown that zenocutuzumab yields promising results for certain cancers. In this trial, participants with non-small cell lung cancer (NSCLC) harboring NRG1 fusion will receive zenocutuzumab combined with afatinib. Studies found that patients receiving this combination lived without their cancer worsening for an average of 6.8 months, and 72% experienced tumor shrinkage, indicating potential effectiveness. Meanwhile, participants with advanced prostate cancer (mCRPC) that no longer responds to hormone therapy will receive zenocutuzumab with either enzalutamide or abiraterone with prednisone. Previous studies showed that patients with advanced prostate cancer had a response lasting an average of 11.1 months. These findings suggest zenocutuzumab could be a helpful treatment option for these cancers. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

Adults with specific cancers (NRG1+ NSCLC or mCRPC) who have tried standard treatments without success, or those for whom standard treatments are not suitable. Participants must be in good physical condition, with a life expectancy of at least 12 weeks and normal heart function. They should have no serious infections like hepatitis B/C or HIV, no recent heart attacks, and must agree to use contraception.

Inclusion Criteria

My blood counts and organ functions are within the required ranges.

Signed informed consent before initiation of any study procedures

Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram (ECHO) or multi-gated acquisition scan (MUGA)

Exclusion Criteria

I do not have active hepatitis B, untreated hepatitis C, or HIV.

I had a heart attack less than 6 months ago.

I have serious heart issues, but not atrial fibrillation or brief, sudden heart palpitations.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive zenocutuzumab in combination with afatinib or AR targeting agents, with an initial safety run-in phase followed by an expansion phase

9 months

Intravenous infusion every 2 weeks

Safety Follow-up

Participants are monitored for safety and tolerability of the treatment

6 months

Long-term Follow-up

Participants are monitored for long-term efficacy and survival outcomes

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Zenocutuzumab

Trial Overview The trial is testing Zenocutuzumab alone or combined with other cancer drugs (Afatinib, Enzalutamide, Abiraterone acetate) on patients with NRG1+ non-small cell lung cancer (NSCLC) or metastatic castration-resistant prostate cancer (mCRPC). It's an open-label study where everyone knows what treatment they're getting.

How Is the Trial Designed?

Group I: Part 2: mCRPC Experimental Treatment 3 Interventions

Participants will receive intravenous infusion of 750 mg of zenocutuzumab once every 2 weeks in combination with the AR targeting agent they experienced disease progression on prior to study entry: enzalutamide 160 mg orally once daily or abiraterone 1000 mg orally once daily with prednisone 5 mg orally twice daily

Group II: Part 2: NSCLC harboring NRG1+ fusion Experimental Treatment 2 Interventions

Participants will receive intravenous infusion of 750 mg of zenocutuzumab once every 2 weeks in combination with afatinib 40 mg orally once daily.

Group III: Part 1: mCRPC Experimental Treatment 3 Interventions

Participants will receive intravenous infusion of 750 mg of zenocutuzumab once every 2 weeks in combination with the AR targeting agent they experienced disease progression on prior to study entry: enzalutamide 160 mg orally once daily or abiraterone 1000 mg orally once daily with prednisone 5 mg orally twice daily.

Group IV: Part 1: NSCLC harboring NRG1+ fusion Experimental Treatment 2 Interventions

Participants will receive intravenous infusion of 750 mg of zenocutuzumab once every 2 weeks in combination with afatinib 40 mg orally once daily.

Who Is Running the Clinical Trial?

Merus N.V.

Lead Sponsor

Trials

10

Recruited

2,700+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39908431/

Efficacy of Zenocutuzumab in NRG1 Fusion-Positive Cancer Conclusions: Zenocutuzumab showed efficacy in patients with advanced NRG1 fusion-positive cancer, notably NSCLC and pancreatic cancer, with ...

2. nejm.org nejm.org/doi/10.1056/NEJMoa2405008

Efficacy of Zenocutuzumab in NRG1 Fusion–Positive Cancer The median progression-free survival was 6.8 months (95% CI, 5.5 to 9.1). Adverse events were primarily grade 1 or 2. The most common adverse ...

3. lungcancerstoday.com lungcancerstoday.com/post/phase-2-enrgy-trial-zenocutuzumab-shows-efficacy-in-nrg1-fusion-positive-nsclc

Phase 2 eNRGy Trial: Zenocutuzumab Shows Efficacy in ... Zenocutuzumab showed efficacy in patients with advanced NRG1 fusion–positive cancer, including those with non–small cell lung cancer (NSCLC),

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534%2823%2903186-1/fulltext

1315MO Durable efficacy of zenocutuzumab, a HER2 x ... In this updated analysis, Zeno provides robust and durable efficacy in advanced NRG1+ NSCLC, with a well-tolerated safety profile.

5. nature.com nature.com/articles/s41392-025-02283-y

targeting Neuregulin 1 fusions in solid tumors The median progression-free survival (PFS) was 6.8 months (95% CI, 5.5–9.1 months). Tumor regression was observed in 72% of the participants ...

6. nejm.org nejm.org/doi/abs/10.1056/NEJMoa2405008

Efficacy of Zenocutuzumab in NRG1 Fusion–Positive Cancer Responses were observed in multiple tumor types — including in 27 of 93 patients (29%; 95% CI, 20 to 39) with non–small-cell lung cancer (NSCLC) ...

7. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zenocutuzumab-zbco-non-small-cell-lung-cancer-and-pancreatic

FDA grants accelerated approval to zenocutuzumab-zbco On December 4, 2024, the FDA granted accelerated approval to zenocutuzumab-zbco for non-small cell lung cancer and pancreatic adenocarcinoma.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11878197/

Efficacy of Zenocutuzumab in NRG1 Fusion-Positive Cancer Panel B shows a swimmer plot of outcomes, including time to response, duration of exposure, and patient status in 161 patients in the primary efficacy set.

9. partnertx.com partnertx.com/new-england-journal-of-medicine-publishes-results-of-global-multicenter-enrgy-study-evaluating-zenocutuzumab-zbco-bizengri-in-nrg1-cancer/

New England Journal of Medicine Publishes Results ... The eNRGy trial evaluated overall response rate to zenocutuzumab-zbco in patients with NRG1 gene fusions across multiple tumor types.