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

Inclusion Criteria:

• At least one measurable lesion according to RECIST v1.1 OR evaluable disease for alimited number of patients (up to 15) in Group H;

• Performance status of ECOG 0 - 2;

• Estimated life expectancy of at least 12 weeks;

• Toxicities incurred as a result of previous anti-cancer therapy resolved to ≤Grade 1;

• Treatment with anti-cancer medication or investigational drugs within the followingintervals before the first dose of MCLA-128:

1. more than 14 days or more than 5 half-lives prior to study entry, whichever isshorter.

2. more than 14 days for radiotherapy.

• Recovery from major surgery or other complication to ≤ Grade 2 or baseline ;

• Absolute neutrophil count ≥1.5 x 109/L without colony stimulating factor support forat least 7 days prior to screening;

• Platelets ≥75 x 109/L without transfusion support for at least 7 days prior toscreening;

• Hemoglobin ≥8 g/dL or ≥5 mmol/L;

• Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤3 x upper limit ofnormal (ULN) and total bilirubin ≤1.5 x ULN; in cases of metastatic liverinvolvement, ALT/AST ≤5 x ULN and total bilirubin ≤2 x ULN will be allowed; in casesof antecedents of Gilbert's syndrome when total bilirubin ≤3.0 x ULN or directbilirubin ≤1.5 x ULN will be allowed;

• Estimated glomerular filtration rate (GFR) of more than 30 mL/min

• Able to provide a tumor biopsy sample (fresh strongly preferred or else archival);

• Not pregnant or nursing

• Fertile patients must use effective contraception during and for 6 month aftercompletion of study therapy;

• Patients must have received prior standard therapy appropriate for their tumor typeand stage of disease, or in the opinion of the Investigator, would be unlikely totolerate or derive clinically meaningful benefit from appropriate standard of caretherapy or no satisfactory alternative treatment options are available;

• Locally-advanced unresectable or metastatic solid tumor malignancy with documentedNRG1 gene fusion, identified through molecular assays such as next generationsequencing-based assays [DNA or RNA], as routinely performed at CLIA or othersimilarly-certified laboratories.

Exclusion Criteria:

• Pregnant or lactating;

• Presence of an active uncontrolled infection or an unexplained fever;

• Known hypersensitivity to any of the components of MCLA-128;

• Known HIV, active Hepatitis B without receiving antiviral treatment, or Hepatitis C;patients treated for Hepatitis C and have undetectable viral loads are eligible

• Known symptomatic or unstable brain metastases;

• Patients with leptomeningeal metastases;

• Presence of LVEF below 50% on the screening echocardiogram; or history or presenceof any significant cardiovascular disease, including unstable angina or myocardialinfarction within 12 months prior to screening, congestive heart failure (NYHA ClassIII or IV), or ventricular arrhythmia requiring medication;

• Previous or concurrent malignancy (excluding non-basal cell carcinoma of skin orcarcinoma in situ of the uterine cervix) unless the tumor was treated with curativeintent more than 2 years prior to study entry;

• Presence of any other medical or psychological condition deemed by the Investigatorto be likely to interfere with a patient ability to sign informed consent, cooperateor participate in the study, or interfere with the interpretation of the results.