Sym004 in Combination With FOLFIRI in Metastatic Colorectal Cancer Patients

In the Phase 1b (Dose-Escalation) portion of the trial, patients will be sequentially
enrolled to dose-escalation cohorts until establishment of the Maximum Tolerated Dose (MTD)
and/or Recommended Phase 2 Dose (RP2D) of Sym004 in combination with FOLFIRI.

The Phase 2a (Dose-Expansion) portion of the trial is expected to begin after establishing
the RP2D.

Note: In January 2017, the trial was terminated during Phase 1b and enrollment was
prematurely discontinued. The primary objective changed to assess the safety of the treatment
combination; collection of data for secondary and exploratory objectives was omitted.

Main inclusion Criteria:

1. Male or female, at least 18 years of age at the time of informed consent

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

3. Histologically or cytologically confirmed, locally advanced or metastatic colorectal
cancer (CRC) that is documented to be without Kirsten rat sarcoma (KRAS) or
neuroblastoma rat sarcoma (NRAS) gene mutations (i.e., tumors must express the KRAS
and NRAS wild type [WT], exon 2, 3 and 4).

4. Failed (defined as radiologic progression) treatment for locally advanced or
metastatic disease with first-line combination therapy of oxaliplatin and a
fluoropyrimidine, with or without bevacizumab, during treatment or < 3 months after
the last dose of first-line therapy and within < 3 months of C1/D1. Patients who
discontinued first-line therapy due to toxicity may be enrolled provided progression
occurred < 6 months after the last dose of the first-line therapy regimen.

or Failed (defined as radiologic progression) adjuvant therapy with combination
therapy of oxaliplatin and a fluoropyrimidine during treatment or within < 6 months
after the last dose of oxaliplatin and within < 6 months of C1/D1.

5. Eligible for FOLFIRI

6. Measurable disease according to RECIST v1.1

Main exclusion Criteria:

1. Prior therapy with anti-EGFR antibodies, anti-EGFR small molecule inhibitors or
irinotecan (CPT-11)

2. Any antineoplastic agent (standard or investigational) within 4 weeks prior to C1/D1

3. Significant gastrointestinal abnormalities

4. Patients with a significant cardiovascular disease or condition

5. Abnormal hematologic, renal or hepatic function