Sym015 (Anti-MET) in Patients With Advanced Solid Tumor Malignancies

In the first part of the study (Part 1, dose-escalation), Sym015 will be evaluated for safety
and tolerability. Additionally, the recommended Phase 2 dose (RP2D) will be determined.
Sym015 will be given at different dose levels on an every second week (Q2W) dosing schedule.
Each patient will be given one fixed dose level.

In the second part of the study (Part 2, dose-expansion), dosing will be at the RP2D on a Q2W
dosing schedule. Three cohorts will be included:

- Basket Cohort: Patients with KRAS wild-type (WT) advanced solid tumor malignancies with
MET-amplification and without therapeutic options. Patients must have no prior therapy
with MET-targeting agents, except a subset of patients having received prior therapy
with a MET-targeting tyrosine kinase inhibitor (TKI). As of December 2018, accrual to
this cohort is suspended.

- Non-Small Cell Lung Carcinoma (NSCLC) MET-Amplified Cohort: Patients with advanced NSCLC
with MET-amplification, and without available therapeutic options. Patients may have
received prior therapy with MET-targeting and/or epidermal growth factor receptor
(EGFR)-targeting agents.

- NSCLC with MET exon 14 skipping alteration (METex14del) Cohort: Patients with advanced
NSCLC METex14del, and without therapeutic options. Tumors need not be MET-amplified, and
patients may have received prior therapy with MET-targeting and/or EGFR-targeting
agents.

Inclusion Criteria:

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

- Life expectancy >3 months assessed during Screening.

- Documented (histologically- or cytologically-proven) solid tumor malignancy that is
locally advanced or metastatic, and that is refractory to standard therapy or for
which no standard therapy is available or accessible.

- If female and of childbearing potential: a negative pregnancy test.

- Male or female: either not of childbearing potential or agreeing to use a medically
effective method of contraception as per institutional standards during the trial and
for 4 months after the last dose of trial drug.

- Part 1 ONLY: Tumor documented to be KRAS WT by local assessment.

- Part 2 ONLY:

- Measurable disease according to RECIST v1.1 that has been confirmed by computed
tomography (CT) or magnetic resonance imaging (MRI) within 4 weeks prior to Cycle
1/Day 1 (C1/D1).

- Basket Cohort ONLY:

- Tumor documented to be KRAS WT by local assessment according to
institutional standards. If KRAS WT is not previously documented and if
archival tissue is not available for pretrial assessment, patient must be
willing to undergo a tumor biopsy to confirm eligibility.

- Confirmed MET-amplification by local assessment.

- No prior therapy with MET-targeting agents (except a subset of patients
having received prior therapy with a MET-targeting TKI).

- Willingness to undergo a pre- and post-dosing biopsy (maximum of 2 biopsies)
from primary or metastatic tumor site(s) considered safely accessible for
biopsy

- NSCLC MET-Amplified Cohort ONLY:

- Documented NSCLC meeting disease criteria as defined per protocol.

- Documented MET-amplification.

- May have received prior therapy with MET-targeting and/or EGFR-targeting
agents (antibodies or TKIs).

- Willingness to undergo a pre-dosing biopsy (mandatory unless a recent tumor
biopsy is available), and potentially a biopsy at the End of Cycle 2 (EOC2)
(optional), from a primary or metastatic tumor site considered safely
accessible for biopsy.

- NSCLC METex14del Cohort ONLY:

- Documented NSCLC meeting disease criteria as defined per protocol.

- Documented METex14del (tumors need not be MET-amplified).

- May have received prior therapy with MET-targeting and/or EGFR-targeting
agents (antibodies or TKIs).

- Willingness to undergo a pre-dosing biopsy (mandatory unless a recent tumor
biopsy is available), and potentially a biopsy at the EOC2 (optional), from
a primary or metastatic tumor site considered safely accessible for biopsy.

Exclusion Criteria:

- Any antineoplastic agent for the primary malignancy (standard or investigational)
without delayed toxicity within 4 weeks or 5 plasma half-lives, whichever is shortest,
prior to C1/D1, except nitrosoureas and mitomycin C within 6 weeks prior to C1/D1.

- Immunosuppressive or systemic hormonal therapy within 2 weeks prior to C1/D1, with
exceptions.

- Use of hematopoietic growth factors within 2 weeks prior to C1/D1.

- Active second malignancy or history of another malignancy within the last 3 years,
with exceptions.

- Central nervous system (CNS) malignancy including primary malignancies of the CNS and
known, untreated CNS or leptomeningeal metastases, or spinal cord compression;
patients with any of these not controlled by prior surgery or radiotherapy, or
symptoms suggesting CNS involvement for which treatment is required.

- Inadequate recovery from an acute toxicity associated with any prior antineoplastic
therapy.

- Major surgical procedure within 4 weeks prior to C1/D1 or inadequate recovery from any
prior surgical procedure.

- Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism, within
1 month prior to C1/D1, unless adequately treated and stable.

- Active uncontrolled bleeding or a known bleeding diathesis.

- Significant cardiovascular disease or condition.

- Abnormal hematologic, renal or hepatic function.

- Part 2 ONLY:

- Radiotherapy against target lesions within 4 weeks prior to C1/D1, unless there
is documented progression of the lesion following the radiotherapy.

- Basket Cohort ONLY:

- Prior therapy with MET-inhibiting agents (exceptions will be a subset of
patients that will be entered to the Basket Cohort after having received
prior therapy with a MET-targeting TKI).

- Prior therapy with antibody to hepatocyte growth factor (HGF).

- Basket Cohort and NSCLC MET-Amplified Cohort ONLY:

- Tumor status demonstrating MET-polysomy in the absence of MET-amplification,
as specified per protocol. Patients in the NSCLC METex14del Cohort with
polysomy are eligible.