A Study of Bispecific Antibody MCLA-158 in Patients With Advanced Solid Tumors

Study Design:

This open label, multicenter, first-in-human study consists of 2 parts. Part 1 is a dose
escalation to find the recommended Phase II dose (RP2D) of MCLA-158 studying patients with
metastatic colorectal cancer. Part 2 is a dose expansion cohort studying MCLA-158 in
colorectal cancer and other solid tumor indications.

In the dose escalation part, patients with metastatic colorectal cancer previously treated
with up to 4 lines of prior therapy in the metastatic setting including oxaliplatin-based and
irinotecan-based chemotherapy, with or without an anti-angiogenic and with or without an
anti-EGFR if RAS wild-type (RASwt).

In the expansion part, MCLA-158 will be administered at the RP2D in metastatic colorectal
patients and selected non-colorectal indications in advanced solid tumors. The expansion part
will further characterize the safety, PK, immunogenicity and preliminary antitumor activity
of single-agent MCLA-158 will be in all patients, and retrospective biomarker analyses
including EGFR and LGR5 status will be performed.

The study consists of three periods: Screening (up to 28 days prior to the first dose of
study drug); Treatment (first dose of study drug with treatment cycles of 28 days); and
Follow-up (through 30 days after the last dose and and quarterly checks for survival data up
to 12 months).

Inclusion Criteria:

- Histologically or cytologically confirmed solid tumors with evidence of metastatic or
locally disease not amenable to standard therapy with curative intent with patients
with metastatic colorectal cancer treated in the metastatic setting with standard
approved therapy including oxaliplatin, irinotecan and fluoropyrimidines (5-FU and/or
capecitabine) ± an anti-angiogenic agent ± an anti-EGFR agent.

- A baseline fresh tumor sample (FFPE and if sufficient material also frozen) from a
metastatic or primary site.

- Measurable disease as defined by RECIST version 1.1 by radiologic methods.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

- Life expectancy ≥ 12 weeks, as per investigator.

- Adequate organ function

Exclusion Criteria:

- Central nervous system metastases that are untreated or symptomatic, or require
radiation, surgery, or continued steroid therapy to control symptoms within 14 days of
study entry.

- Known leptomeningeal involvement.

- Participation in another clinical trial or treatment with any investigational drug
within 4 weeks prior to study entry.

- Any systemic anticancer therapy within 4 weeks or 5 half-lives whichever is longer of
the first dose of study treatment. For cytotoxic agents that have major delayed
toxicity ( e.g. mitomycin C,nitrosoureas), or anticancer immunotherapies, a washout
period of 6 weeks is required.

- Requirement for immunosuppressive medication (e.g. methotrexate, cyclophosphamide)

- Major surgery or radiotherapy within 3 weeks of the first dose of study treatment.
Patients who received prior radiotherapy to ≥25% of bone marrow are not eligible,
irrespective of when it was received.

- Persistent grade >1 clinically significant toxicities related to prior antineoplastic
therapies (except for alopecia); stable sensory neuropathy ≤ grade 2 NCI-CTCAE v4.03
is allowed.

- History of hypersensitivity reaction or any toxicity attributed to human proteins or
any of the excipients that warranted permanent cessation of these agents.

- Uncontrolled hypertension (systolic > 150 mmHg and/or diastolic > 100 mmHg) with
appropriate treatment or unstable angina.

- History of congestive heart failure of Class II-IV New York Heart Association (NYHA)
criteria, or serious cardiac arrhythmia requiring treatment (except atrial
fibrillation, paroxysmal supraventricular tachycardia).

- History of myocardial infarction within 6 months of study entry.

- History of prior malignancies with the exception of excised cervical intraepithelial
neoplasia or nonmelanoma skin cancer, or curatively treated cancer deemed at low risk
for recurrence with no evidence of disease for at least 3 years.

- Current dyspnea at rest of any origin, or other diseases requiring continuous oxygen
therapy.

- Patients with a history of interstitial lung disease (e.g.: pneumonitis or pulmonary
fibrosis) or evidence of ILD on baseline chest CT scan.

- Current serious illness or medical conditions including, but not limited to
uncontrolled active infection,clinically significant pulmonary, metabolic or
psychiatric disorders.

- Active HIV, HBV, or HCV infection requiring specific treatment.

- Pregnant or lactating women; patients of childbearing potential must use highly
effective contraception methods prior to study entry, for the duration of study
participation, and for 6 months after the last dose of MCLA-158.