Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Afatinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

afatinib

Gene fusions are defined as two separate genes joined together (gene 1, gene 2), generating a novel fusion gene. NRG1 fusions are rare and complex with regard to the fusion/fusion partner. The specific NRG1 gene fusion will be identified by a specialized molecular testing lab.

Afatinib is provided on a single-patient protocol basis to patients suffering from tumors harboring NRG1 fusions, a disease for which no satisfactory authorised alternative therapy exists.

In the context of this mechanism it is planned to collect and analyze limited clinical data in order to investigate the safety and efficacy of afatinib in patients with advanced and/or metastatic solid tumours harboring NRG1 gene fusions.

Afatinib (GILOTRIF®) in Patients Suffering From Tumors Harboring Neuregulin 1 (NRG1) Gene Alterations (Specifically NRG1 Gene Fusion-positive Advanced Solid Tumors)

Assessment of Prospective Real-world Outcomes Based on Single-patient Protocol Data Collection of Afatinib (GILOTRIF®) Use in Patients With Solid Tumors Harboring NRG1 Gene Fusions

Boehringer Ingelheim

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

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

Skin and Connective Tissue Diseases

Uterine Cervical Neoplasms

Carcinoma

Breast Neoplasms

Triple Negative Breast Neoplasms

Melanoma

Prostatic Neoplasms

Stomach Neoplasms

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Carcinoma, Hepatocellular

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Urinary Bladder Neoplasms

Endometrial Neoplasms

Neoplasms, Squamous Cell

Urogenital Neoplasms

Genital Diseases

Urogenital Diseases

Neoplasms by Histologic Type

Skin Diseases

Neoplasms, Glandular and Epithelial

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Uterine Neoplasms

Uterine Diseases

Breast Diseases

Esophageal Cancer

Ovarian Cancer

Stomach Cancer

Ovarian Epithelial Cancer

Antibodies, Monoclonal

Groups of patients will receive increasing doses of HMBD-001 as a single agent to find a safe dose that best targets cancer cells. Approximately 26 patients with tumours known to express HER3 will be entered into this arm.

An expansion cohort of up to 25 patients with a confirmed HER3 positive or confirmed NRG1 fusion rearrangement RAS wild type colorectal cancer, castration resistant prostate cancer, triple negative breast cancer or squamous cell head and neck cancer will receive the HMBD-001 single agent RP2D as determined in Part A Arm 1.

Intravenous infusion given over a 21 or 28 day cycle dependent on dosing frequency. Number of cycles: 6 or until disease progression or unacceptable toxicity develops.

HMBD-001

Johann de Bono, Prof

Simon Lord, Dr

Derek Paisley

Johaan de Bono, Prof

This clinical trial is evaluating a drug called HMBD-001 (an anti-HER3 monoclonal antibody) in patients with advanced HER3 positive solid tumours. The main aims are to find out the maximum dose of HMBD-001 that can be given safely to patients alone and in combination with other anti-cancer agents, more about the potential side effects of HMBD-001 and how these can be treated and what happens to HMBD-001 inside the body and how it affects cancer cells.

HMBD-001 is a type of drug called a monoclonal antibody, which works by targeting a protein called HER3, that is found in high numbers in some types of cancers including those which contain NRG1 gene fusions. By attaching itself to this protein it may then work to kill the cancer cells or to stop them growing.

This is a first-in-human clinical trial which has two parts:

Part A is a 'dose escalation' phase where small groups of patients will receive increasing doses of HMBD-001 to find the safest dose which best targets cancer cells.

* In Arm 1, patients will receive HMBD-001 on its own (as a single agent).
* In Arm 2, patients will receive HMBD-001 given with other anti-cancer drugs (in combination).

Part B is a 'dose expansion' phase where larger groups of patients with specific cancer types, known to have high levels of the protein HER3 or a confirmed NRG1 gene fusion will receive the highest doses of HMBD-001 considered to be safe in Part A either alone as single agent or in combination with other anti-cancer drugs.

The main aims of the clinical trial are to find out:

* The highest dose of HMBD-001 alone and in combination with other anti-cancer drugs that can be given safely to patients.
* More about the potential side effects of HMBD-001 when given alone and in combination with other anti-cancer agents and how they can be managed.
* What happens to HMBD-001 inside the body and how it affects cancer cells.
* The potential anti-tumour activity of HMBD-001 as a single agent and in various combination regimens in specific tumour types of HER3 expressing tumours or tumours with NRG1 gene fusions.

HMBD-001 in Advanced HER3 Positive Solid Tumours

HMBD-001 (an Anti-HER3 Monoclonal Antibody) Given Intravenously as a Single Agent and in Combination in Patients With Advanced HER3 Positive Solid Tumours

Recommended dose of HMBD-001 given a) as a single agent and b) in combination with selected anticancer agent(s) with an estimated Dose Limiting Toxicity (DLT) rate that is closest to 25% using a one-stage Bayesian Continual Reassessment Method (CRM)

Number of grade 3, 4 and adverse events related to HMBD-001 given a) as a single agent and b) in combination with selected anti-cancer agent(s) graded according to National Cancer Institute Common Criteria for Adverse Events (NCI CTCAE) Version 5.0

Number of patients achieving a complete response (CR) or partial response (PR) to HMBD-001 based on Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 in the chosen tumour types

Maximum observed plasma concentration (Cmax) of HMBD-001

Terminal elimination half-life (t½) of HMBD-001

Time taken to reach maximum observed concentration (Tmax) of HMBD-001

Volume of distribution of HMBD-001 in plasma

Number of patients achieving a complete response (CR), partial response (PR) or stable disease (SD) based on Response Evaluation Criteria in Solid Tumours (RECIST) v1.1

Number of Patients whose cancer has not progressed at 12 and 24 months

Number of patients who are still alive at 12 and 24 months

Hummingbird Bioscience

Cancer Research UK

Gemcitabine

Paclitaxel

Docetaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Participants with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) harboring NRG1 gene fusions

Participants with non-small cell lung cancer (NSCLC) harboring NRG1 gene fusions

Participants with other solid tumors harboring NRG1 gene fusions

Participants with solid tumors harboring selected HER3 extracellular mutations

HMBD-001 is a humanized IgG1 anti-HER3 monoclonal antibody (mAb). It is administered IV weekly

Docetaxel 75 mg/m\^2 IV once every 3 weeks

Nab-paclitaxel 125 mg/m\^2 IV on days 1, 8, 15, every 4 weeks

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Afatinib (GILOTRIF®) in Patients Suffering From Tumors Harboring Neuregulin 1 (NRG1) Gene Alterations (Specifically NRG1 Gene Fusion-positive Advanced Solid Tumors)	NCT05107193	Solid Tumors	afatinib	18 Years -	Boehringer Ingelheim
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.
HMBD-001 in Advanced HER3 Positive Solid Tumours	NCT05057013	Bladder Cancer Triple Negative... Castration-resi... Cervical Cancer RAS Wild Type C... Endometrial Can... Gastric Cancer Hepatocellular ... Melanoma Non-small Cell ... Oesophageal Can... Ovarian Cancer Pancreatic Canc... Squamous Cell C...	HMBD-001	16 Years -	Cancer Research UK
Study of an Anti-HER3 Antibody, HMBD-001, With or Without Chemotherapy in Patients With Solid Tumors Harboring an NRG1 Fusion or HER3 Mutation	NCT05919537	Non-Small Cell ... Pancreatic Canc... Locally Advance... Metastatic Soli...	HMBD-001 Docetaxel Nab-paclitaxel Gemcitabine	18 Years -	Hummingbird Bioscience
Early Access Program Providing HER2/HER3 Bispecific Antibody, MCLA-128, for a Patient With Advanced NRG1-Fusion Positive Solid Tumor	NCT04100694	NRG1 Fusion Pancreatic Canc... Non Small Cell ... Solid Tumor, Un... Prostate Cancer Head and Neck C... Colorectal Canc... Breast Cancer Cholangiocarcin... Renal Cell Carc... Unknown Primary...	MCLA-128	18 Years -	Merus N.V.
Study of an Anti-HER3 Antibody, HMBD-001, With or Without Chemotherapy in Patients With Solid Tumors Harboring an NRG1 Fusion or HER3 Mutation	NCT05919537	Non-Small Cell ... Pancreatic Canc... Locally Advance... Metastatic Soli...	HMBD-001 Docetaxel Nab-paclitaxel Gemcitabine	18 Years -	Hummingbird Bioscience

Spots Global Cancer Trial Database for nrg1 fusion

Every month we try and update this database with for nrg1 fusion cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for nrg1 fusion

Every month we try and update this database with for nrg1 fusion cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for nrg1 fusion cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.