Zenocutuzumab for Solid Tumors

Recruiting at 64 trial locations

Overseen By Merus Inquiries

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Partner Therapeutics, Inc.

Disqualifiers: Pregnancy, Infection, HIV, Hepatitis, 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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 36 months

250 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called zenocutuzumab in patients with specific genetic changes in their tumors. The goal is to see if the drug can safely and effectively stop the growth of these cancers.

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, you must not have taken any anti-cancer medication or investigational drugs within 14 days or 5 half-lives before the first dose of the study drug, whichever is shorter.

Will I have to stop taking my current medications?

The trial requires that you stop taking any anti-cancer medication or investigational drugs at least 14 days before starting the study treatment. If your current medication is not an anti-cancer drug, the protocol does not specify whether you need to stop it.

What data supports the idea that Zenocutuzumab for Solid Tumors is an effective treatment?

The available research shows that Zenocutuzumab is effective for patients with tumors that have NRG1 gene rearrangements. In a study, two patients with pancreatic cancer and one with lung cancer, all of whom had not responded to previous treatments, showed significant improvement after using Zenocutuzumab. The pancreatic cancer patients experienced rapid relief from symptoms and continued to benefit from the treatment for over a year. The lung cancer patient, who had tried six other treatments without success, also showed a positive response. This suggests that Zenocutuzumab can be a promising option for these specific types of cancer. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Zenocutuzumab for solid tumors?

Zenocutuzumab has shown effectiveness in treating tumors with NRG1 gene rearrangements, particularly in pancreatic cancer and non-small cell lung cancer, by targeting specific proteins (HER2 and HER3) involved in tumor growth. In studies, patients with these types of cancers experienced significant improvements, including reduced tumor size and prolonged treatment response. ^{1 2 3 4 5}

What safety data is available for Zenocutuzumab (MCLA-128) for solid tumors?

The provided research does not contain specific safety data for Zenocutuzumab (MCLA-128) or its other names like Bizengri, Zeno, or zenocutuzumab-zbco. The studies focus on different treatments and imaging agents, such as 89Zr-pertuzumab and pembrolizumab, and do not mention Zenocutuzumab. Therefore, no relevant safety data for Zenocutuzumab is available in the provided research. ^{6 7 8 9 10}

Is Zenocutuzumab (MCLA-128) a promising drug for solid tumors?

Zenocutuzumab (MCLA-128) is considered a promising drug for solid tumors because it is designed to target specific proteins on cancer cells, potentially leading to better treatment outcomes. It is part of a new class of drugs that aim to improve the effectiveness of cancer treatment by precisely targeting cancer cells while sparing healthy ones. ^{3 7 11 12 13}

What makes Zenocutuzumab unique compared to other drugs for solid tumors?

Zenocutuzumab is unique because it is a bispecific antibody that targets both HER2 and HER3 receptors, potentially offering a novel approach for treating solid tumors by simultaneously blocking two pathways involved in cancer cell growth. ^{3 7 11 12 13}

Research Team

Alison Schram, MD

Principal Investigator

Memorial Sloan Kettering Medical Center

Eligibility Criteria

This trial is for adults with advanced solid tumors that have a specific genetic change called an NRG1 fusion. They should have tried standard treatments or be unsuitable for them, and must not be pregnant or breastfeeding. Participants need to have a life expectancy of at least 12 weeks, stable organ function, and no serious heart conditions or uncontrolled infections.

Inclusion Criteria

Your liver enzyme levels and bilirubin levels should be within certain limits. If you have liver spread of cancer, slightly higher levels are allowed. If you have Gilbert's syndrome, higher bilirubin levels are allowed.

I can provide a new or old sample of my tumor for testing.

Not pregnant or nursing

Exclusion Criteria

Pregnant or lactating

I have HIV or untreated Hepatitis B, or I've been treated for Hepatitis C with no detectable virus now.

I have brain metastases that are causing symptoms or are unstable.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive intravenous infusion of 750 mg of zenocutuzumab (MCLA-128) every 2 weeks in 28-day treatment cycles

36 months

Bi-weekly visits for infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment, with quarterly checks for survival data

24 months

Treatment Details

Interventions

• Zenocutuzumab (MCLA-128)

Trial Overview The study tests Zenocutuzumab (MCLA-128), focusing on its safety, how the body processes it, and its effectiveness against tumors with NRG1 fusions. It's an early-stage trial involving dose adjustments to find the right balance between safety and efficacy.

Participant Groups

Group I: Part 2 Solid tumour (basket) harboring NRG1 fusion Experimental Treatment 1 Intervention

Participants will receive intravenous infusion of 750 mg of zenocutuzumab (MCLA-128) (the recommended Phase 2 dose (RP2D)) every 2 weeks.

Group II: Part 2 Pancreatic adenocarcinoma harboring NRG1 fusion Experimental Treatment 1 Intervention

Participants will receive intravenous infusion of 750 mg of zenocutuzumab (MCLA-128) (the recommended Phase 2 dose (RP2D)) every 2 weeks.

Group III: Part 2 NSCLC cancer harboring NRG1 fusion Experimental Treatment 1 Intervention

Participants will receive intravenous infusion of 750 mg of zenocutuzumab (MCLA-128) (the recommended Phase 2 dose (RP2D)) every 2 weeks.

Zenocutuzumab (MCLA-128) is already approved in United States for the following indications:

Approved in United States as Bizengri for:

• Non-small cell lung cancer harboring a neuregulin 1 gene fusion
• Pancreatic adenocarcinoma harboring a neuregulin 1 gene fusion

Who Is Running the Clinical Trial?

Partner Therapeutics, Inc.

Lead Sponsor

Trials

7

Recruited

820+

Merus N.V.

Lead Sponsor

Trials

10

Recruited

2,700+

Findings from Research

Zenocutuzumab (Zeno) is a bispecific antibody that targets both HER2 and HER3, showing promising efficacy in treating NRG1 fusion-positive cancers, as demonstrated in both cell line models and patient cases.

In a small cohort of three patients with chemotherapy-resistant NRG1 fusion-positive cancers, two patients with pancreatic cancer experienced significant and lasting responses to Zeno, remaining on treatment for over 12 months, highlighting its potential as a novel therapeutic option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zenocutuzumab, a HER2xHER3 Bispecific Antibody, Is Effective Therapy for Tumors Driven by NRG1 Gene Rearrangements. Schram, AM., Odintsov, I., Espinosa-Cotton, M., et al.[2023]

Zenocutuzumab, a bispecific antibody, is currently being tested in a phase I/II study and has shown early signs of effectiveness in patients with tumors that have NRG1 fusions.

The treatment appears especially promising for younger patients with NRG1 fusion-positive pancreatic ductal adenocarcinoma, a type of cancer that is often difficult to treat.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zenocutuzumab Shines in PDAC. [2022]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

Patritumab deruxtecan (HER3-DXd) is a promising new treatment for EGFR-mutated non-small cell lung cancer (NSCLC) that has progressed after standard therapies, showing antitumor activity and a tolerable safety profile in an ongoing phase I study.

HER3-DXd targets the HER3 receptor, which is often overexpressed in EGFR-mutated NSCLC, and is currently being further evaluated in a global phase II trial (HERTHENA-Lung01) to confirm its efficacy in patients who have already received other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HERTHENA-Lung01: a phase II study of patritumab deruxtecan (HER3-DXd) in previously treated metastatic EGFR-mutated NSCLC. Yu, HA., Yang, JC., Hayashi, H., et al.[2023]

In a study of 1506 patients with metastatic renal cell carcinoma (mRCC), those treated with the combination of axitinib and pembrolizumab (axi/pembro) showed a median overall survival (OS) of 28.9 months compared to 24.3 months for those treated with ipilimumab and nivolumab (ipi/nivo), although this difference was not statistically significant for the entire population.

Patients with favorable risk disease (IMDC favorable risk strata) experienced improved survival with axi/pembro, suggesting that this combination may be particularly beneficial for certain patient groups, even though overall survival rates were similar across both treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Effectiveness of Front-Line Ipilimumab and Nivolumab or Axitinib and Pembrolizumab in Metastatic Clear Cell Renal Cell Carcinoma. Zarrabi, KK., Handorf, E., Miron, B., et al.[2023]

This first-in-human study involving 6 patients with HER2-positive metastatic breast cancer demonstrated that 89Zr-pertuzumab PET/CT is safe, with no reported toxicities during the trial.

The imaging technique effectively visualized HER2-positive metastases, confirming its potential for assessing HER2 status in lesions that are difficult to biopsy, and it accurately identified HER2-positive brain metastases in one patient, which was later confirmed by surgical resection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human Human Epidermal Growth Factor Receptor 2-Targeted Imaging Using 89Zr-Pertuzumab PET/CT: Dosimetry and Clinical Application in Patients with Breast Cancer. Ulaner, GA., Lyashchenko, SK., Riedl, C., et al.[2019]

89Zr-matuzumab was developed as a PET imaging probe to monitor treatment responses in colorectal cancer, showing high uptake in EGFR-positive tumors and confirming its binding to noncompeting epitopes of EGFR.

The nimotuzumab-PEG6-DM1 antibody-drug conjugate demonstrated significantly improved efficacy in targeting colorectal cancer cells, achieving complete tumor remission in 2 out of 3 mice treated, indicating its potential as an effective therapeutic option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous Imaging and Therapy Using Epitope-Specific Anti-Epidermal Growth Factor Receptor (EGFR) Antibody Conjugates. Tikum, AF., Nambisan, AK., Ketchemen, JP., et al.[2022]

The study successfully developed an immuno-PET imaging agent, 89Zr-DFO-pertuzumab, which effectively binds to HER2 and allows for visualization of HER2-expressing tumors, demonstrating its potential to monitor therapeutic responses in breast cancer.

In trastuzumab-resistant JIMT-1 breast cancer models, 89Zr-DFO-pertuzumab showed significantly reduced uptake in tumors treated with the HSP90 inhibitor 17-DMAG, indicating its ability to assess treatment efficacy and HER2 downregulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Response Monitoring with 89Zr-DFO-Pertuzumab in HER2-Positive and Trastuzumab-Resistant Breast Cancer Models. Kang, M., Shin, JI., Han, S., et al.[2022]

In a phase II study involving 110 patients with advanced clear cell renal cell carcinoma (ccRCC), pembrolizumab demonstrated a 36.4% objective response rate, indicating significant antitumor activity as a first-line treatment.

The treatment was generally well-tolerated, with 30% of patients experiencing grade 3-5 adverse events, primarily colitis and diarrhea, which aligns with safety profiles observed in other cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-Label, Single-Arm Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Clear Cell Renal Cell Carcinoma. McDermott, DF., Lee, JL., Bjarnason, GA., et al.[2022]

In a pilot study involving 6 patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL), the use of 89Zr-labeled rituximab-PET showed a positive correlation between tumor uptake of the imaging agent and CD20 expression in tumor biopsies, suggesting it could serve as a useful imaging biomarker for assessing CD20 targeting.

The study found that intense tumor uptake of 89Zr-rituximab corresponded with positive CD20 expression in most patients, indicating that this imaging technique may help predict the effectiveness of rituximab therapy, although further research is needed to confirm these findings and their clinical implications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Performance of 89Zr-Labeled-Rituximab-PET as an Imaging Biomarker to Assess CD20 Targeting: A Pilot Study in Patients with Relapsed/Refractory Diffuse Large B Cell Lymphoma. Jauw, YW., Zijlstra, JM., de Jong, D., et al.[2018]

Polatuzumab vedotin is an antibody-drug conjugate that has shown significant clinical activity and an acceptable safety profile in treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL), particularly when combined with anti-CD20 monoclonal antibodies and chemotherapy.

The recent POLARIX trial suggests that polatuzumab may also be effective in frontline treatment for DLBCL, potentially changing its role in managing patients who have not responded to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin in relapsed / refractory aggressive B-cell lymphoma. Varma, G., Wang, J., Diefenbach, C.[2022]

In phase I trials, matuzumab showed some efficacy in treating EGFR-positive cancers, with a 23% response rate in patients with advanced non-small cell lung cancer (NSCLC) when combined with paclitaxel.

Panitumumab did not demonstrate any benefit in NSCLC patients in a randomized phase II trial, and the absence of a biomarker to identify responsive patients limits its further investigation in this cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibodies to the epidermal growth factor receptor in non small cell lung cancer: current status of matuzumab and panitumumab. Socinski, MA.[2019]

In a phase 3 trial involving 879 patients with untreated intermediate-risk or high-risk diffuse large B-cell lymphoma (DLBCL), the modified regimen pola-R-CHP (which replaces vincristine with polatuzumab vedotin) showed a significantly higher progression-free survival rate at 2 years (76.7%) compared to the standard R-CHOP regimen (70.2%).

The overall survival rates at 2 years were similar between the pola-R-CHP and R-CHOP groups (88.7% vs. 88.6%), indicating that while pola-R-CHP may reduce the risk of disease progression, it does not significantly improve overall survival compared to the standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. Tilly, H., Morschhauser, F., Sehn, LH., et al.[2022]

References

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

Zenocutuzumab, a HER2xHER3 Bispecific Antibody, Is Effective Therapy for Tumors Driven by NRG1 Gene Rearrangements. [2023]

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

Zenocutuzumab Shines in PDAC. [2022]

3. France pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]

4. England pubmed.ncbi.nlm.nih.gov

HERTHENA-Lung01: a phase II study of patritumab deruxtecan (HER3-DXd) in previously treated metastatic EGFR-mutated NSCLC. [2023]

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

Comparative Effectiveness of Front-Line Ipilimumab and Nivolumab or Axitinib and Pembrolizumab in Metastatic Clear Cell Renal Cell Carcinoma. [2023]

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

First-in-Human Human Epidermal Growth Factor Receptor 2-Targeted Imaging Using 89Zr-Pertuzumab PET/CT: Dosimetry and Clinical Application in Patients with Breast Cancer. [2019]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Simultaneous Imaging and Therapy Using Epitope-Specific Anti-Epidermal Growth Factor Receptor (EGFR) Antibody Conjugates. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Therapeutic Response Monitoring with 89Zr-DFO-Pertuzumab in HER2-Positive and Trastuzumab-Resistant Breast Cancer Models. [2022]

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

Open-Label, Single-Arm Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Clear Cell Renal Cell Carcinoma. [2022]

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

Performance of 89Zr-Labeled-Rituximab-PET as an Imaging Biomarker to Assess CD20 Targeting: A Pilot Study in Patients with Relapsed/Refractory Diffuse Large B Cell Lymphoma. [2018]

11. England pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin in relapsed / refractory aggressive B-cell lymphoma. [2022]

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

Antibodies to the epidermal growth factor receptor in non small cell lung cancer: current status of matuzumab and panitumumab. [2019]

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

Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. [2022]