Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

All Drugs and Chemicals

Antibodies

Antibodies, Bispecific

Immunoglobulins

Immunologic Factors

Immunoglobulin G

Immunoglobulins, Intravenous

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

full length IgG1 bispecific antibody targeting HER2 and HER3

zenocutuzumab (MCLA-128)

Merus Inquiries

Paul La Porte

Misako Nagasaka, MD

Christopher Chen, MD

Charles Redfern

Stephen Liu, MD

Luis Raez, MD

Study Coordinator

Bruce Bank

James Cleary, MD

Jaclyn Ventimiglia

Mohammed Najeeb Al Hallak

Alison Schram, MD

Alison Schram

Jordi Rodon, MD

Jordi Rodon

Study Staff

Sara Sandefur

Richard Greil, MD

Jeroen Dekervel, MD

Erika Tsang, MD

Kristoffer Rohrberg

Philippe Cassier, MD

Michael Duruisseaux, MD

Elodie Zedouard

Antoine Hollebecque, MD

Marie Wislez, MD

Cindy Neuzillet, MD

Dirk Arnold, MD

Claas Wesseler, MD

Christoph Springfeld, MD

Nir Peled, MD

Talia Golan, MD

Michele Reni, MD

Salvatore Siena, Prof

Giovanna Marrapese

Federico Cappuzzo, MD

Chigusa Morizane, MD

Yu Sunakawa, MD

Kazumi Nishino, MD

Koichi Goto, MD

Joon Oh Park, MD

Kim Dong-Wan, MD

Sun Young Rha, MD

Frans Opdam, MD

Hanneke Wilmink, MD

Elske Gootjes, MD

Ellis van Liempt

Eelke Gort, MD

Tormod Guren, Dr.

Daniel Shao Weng, MD

Justina Lam, MD

Elisabet Tebe

Teresa Macarulla, MD

Adriana Armellini

Victor Moreno, Dr.

Esther Ordoñez

Irene Moreno, Dr.

Luis Paz-Ares, MD

Miguel Fernandez de Sanmamed Gutierrez, MD

Desamparados Roda, MD

Jeffrey Yachnin, MD

James Yang Chih-Hsin, MD

James Yang Chih-Hsin

Elisa Fontana, MD

This is a Phase I/II, open-label, multi-center, multi-national, dose escalation, single agent study to assess the safety, tolerability, PK, PD, immunogenicity and anti-tumor activity of zenocutuzumab (MCLA-128) in patients with solid tumors harboring an NRG1 fusion (eNRGy)

Study Design :

This open label (all participants know the identity of the study drug), multicenter (more than one study site), first-in-human study consisting of 2 parts. Part 1 is a dose escalation and Part 2 is a dose expansion cohort. Part 1 has been completed.

Part 2 new patient populations examined:

* Group F: Patients with NSCLC with documented NRG1 fusion
* Group G: Patients with pancreatic adenocarcinoma with documented NRG1 fusion
* Group H: Patients with any other solid tumor with documented NRG1 fusion

For these new patient populations, Part 2 will further characterize the safety and tolerability of the selected dose level of zenocutuzumab (MCLA-128), as well as assessment of CBR, defined as the proportion of patients with a CR, PR or durable SD (SD for at least 24 weeks in duration). For the new patient populations, overall response rate (ORR) and duration of response (DOR) will be described.

The study consists of 3 periods: Screening period (up to 28 days prior to the first dose of study drug); Treatment period (treatment cycles of 28 days); and Follow Up period (through 30 days after the last dose and quarterly checks for survival data for up to 2 years). Participants' safety will be monitored throughout the study.

A Study of Zenocutuzumab (MCLA-128) in Patients With Solid Tumors Harboring an NRG1 Fusion (eNRGy)

A Phase I/II Study of MCLA-128, a Full Length IgG1 Bispecific Antibody Targeting HER2 and HER3, in Patients With Solid Tumors (eNRGy)

Evaluation of clinical benefit assessed by RECIST v1.1 determining objective overall response rate (ORR)

To assess durability of anti-tumor activity of MCLA-128 in patients with NRG1 fusions as assessed locally

Assess the anti-tumor response of zenocutuzumab (MCLA-128) by RECIST v1.1 as assessed centrally

CBR assessed as the proportion of patients in whom a complete response (CR) or partial response (PR) or stable disease (SD) is observed (where SD duration is a minimum of 24 weeks) by RECIST v1.1 .

To assess durability of anti-tumor activity of MCLA-128 in patients with NRG1 fusions as assessed centrally

To assess time to onset of response in patients with NRG1 fusions as assessed locally

To assess time to onset of response in patients with NRG1 fusions as assessed centrally

Number of participants with Adverse Events (AE) and Serious Adverse Events (SAE)

Assess the Cmax of zenocutuzumab (MCLA-128)

Assess the volume of distribution of zenocutuzumab (MCLA-128)

Assess the volume of distribution of zenocutuzumab (MCLA-128) at steady state

Assess the Area under the concentration versus time curve from time zero to time t \[AUC0-t\] of zenocutuzumab (MCLA-128)

Assess the half-life of zenocutuzumab (MCLA-128)

Assess the area under the concentration versus time curve \[AUC0-∞\] of zenocutuzumab (MCLA-128)

Assess the time to reach maximum concentration \[tmax\] of zenocutuzumab (MCLA-128)

Assess the Incidence of anti-drug antibodies against zenocutuzumab (MCLA-128)

Assess serum titers of anti-drug antibodies

Merus N.V.

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Antineoplastic Agents

Anti-Inflammatory Agents

Amino Acids

Androgens

Abiraterone Acetate

Prednisone

Mitogens

Afatinib

Androgen Receptor Antagonists

Enzyme Inhibitors

Hormones

Hormone Antagonists

Cytochrome P-450 Enzyme Inhibitors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

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

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.

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

anti epidermal growth factor receptor (EGFR)/HER2 agent

Afatinib Oral Tablet

second-generation androgen receptor antagonist

Enzalutamide Pill

Abiraterone acetate tablets

MCLA-128

Shekeab Jauhari, MD

Paul La Porte, MD

Alexander Philipovskiy, MD, PhD

Mark Goldstein, MD

Leslie Cheteyan

Wassim Abida, MD, PhD

Benjamin Kuritzky, MD

Pedro Barata, MD

Stephan D Kendall, MD

Li Zhang, MD

This is a Phase II, open-label, 2-arm, multicenter, international study designed to evaluate the efficacy of zenocutuzumab alone or in combination in patients with the following diagnoses:

Group A: NRG1+ NSCLC Group B: mCRPC

Study Design:

This is an open label (all participants know the identity of the study drug), multicenter (more than one study site), study consisting of 2 parts:

Group A (NRG1+ NSCLC): Approximately 50 NRG1+NSCLC patients will be enrolled and will receive zenocutuzumab in combination with afatinib 40 mg orally once daily.

Group B (mCRPC): Up to 40 mCRPC patients will be enrolled and will receive zenocutuzumab in combination with the AR targeting agent enzalutamide or abiraterone on which they experienced disease progression immediately before study entry.

For the administration of zenocutuzumab in combination in Groups A and B, the Treatment Period will include 2 phases, an initial safety run-in phase, and an expansion phase with an interim efficacy analysis.

The study will consist of 4 periods: Screening, Treatment, Safety Follow-up, and Long-term Follow up.

Study Evaluating Zenocutuzumab in Patients With or Without Molecularly Defined Cancers

A Phase 2 Study Evaluating Activity of Zenocutuzumab (MCLA-128) in Patients With or Without Molecularly Defined Cancers

Objective Response Rate (ORR) by local assessment per RECIST v1.1

Objective Response Rate (ORR) per RECIST v1.1

Duration of Response (DOR) per RECIST v1.1

Progression-free Survival (PFS) per RECIST v1.1

Frequency and nature of adverse events (AEs) that are related to treatment as assessed by Common Terminology Criteria for AEs (CTCAE) version 5.0

Incidence of antidrug antibodies against zenocutuzumab

Serum titers of antidrug antibodies against zenocutuzumab

Radiographic Progression Free Survival (rPFS) by local investigator per Prostate Cancer Clinical Trials Working Group 3 Modified Response Evaluation Criteria in Solid Tumors (PCWG3-modified RECIST) v1.1 and Overall Survival (OS)

Duration of Response (DOR) per PCWG3-modified RECIST v1.1

Time to Response (TTR) per PCWG3-modified RECIST v1.1

time to Prostate-specific antigen (PSA) progression per PCWG3-modified RECIST v1.1

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Zenocutuzumab (MCLA-128) in Patients With Solid Tumors Harboring an NRG1 Fusion (eNRGy)	NCT02912949	Solid Tumours H... NSCLC Harboring... Pancreatic Canc... NRG1 Fusion	zenocutuzumab (...	18 Years -	Merus N.V.
A Study of Zenocutuzumab (MCLA-128) in Patients With Solid Tumors Harboring an NRG1 Fusion (eNRGy)	NCT02912949	Solid Tumours H... NSCLC Harboring... Pancreatic Canc... NRG1 Fusion	zenocutuzumab (...	18 Years -	Merus N.V.
Study Evaluating Zenocutuzumab in Patients With or Without Molecularly Defined Cancers	NCT05588609	NSCLC Harboring... Metastatic Cast...	Afatinib Oral T... Enzalutamide Pi... Abiraterone ace... MCLA-128	18 Years -	Merus N.V.

Spots Global Cancer Trial Database for nsclc harboring nrg1 fusion