Sym004 in Combination With FOLFIRI in Metastatic Colorectal Cancer Patients

Symphogen

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Metastatic Colorectal Cancer

Treatments: Drug: Sym004; Drug: FOLFIRI

Study type: Interventional

Funder types: Industry

Identifiers

NCT02568046

Sym004-09

2015-003047-19 (EudraCT Number)

Details and patient eligibility

About

This is a Phase 1b/2a study investigating the safety and efficacy of Sym004, an investigational medicinal product (IMP), in combination with FOLFIRI (chemotherapy) when administered every second week (Q2W).

Full description

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.

Enrollment: 10 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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10 participants in 3 patient groups

Sym004 12 mg/kg + FOLFIRI

Experimental group

Description:

Phase 1b, Dose-Escalation: Dose Level 1

Treatment:

Drug: Sym004

Drug: FOLFIRI

Sym004 9 mg/kg + FOLFIRI

Experimental group

Description:

Phase 1b, Dose-Escalation: Dose Level -1

Treatment:

Drug: Sym004

Drug: FOLFIRI

Sym004 (RP2D) + FOLFIRI

Experimental group

Description:

Phase 2a, Dose-Expansion: Sym004 in the RP2D in combination with FOLFIRI

Treatment:

Drug: Sym004

Drug: FOLFIRI