An Open-label, Multi-center Phase I Dose Escalation Study to Investigate the Safety and Tolerability of Multiple Doses of Sym004 in Patients With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- Sym004
- Conditions
- Metastatic Colorectal Cancer
- Sponsor
- Symphogen A/S
- Enrollment
- 111
- Locations
- 7
- Primary Endpoint
- Number of Participants With Adverse Events (AEs)
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
This trial is designed as a multi-centre, open label, dose-escalation, phase I trial and consists of five parts.
Detailed Description
Part A investigates the safety and pharmacokinetics (PK) of escalating weekly dosing of Sym004 in patients with recurrent advanced solid tumors. Part B and C validates the safety, PK and efficacy of weekly dosing of Sym004 at the maximum tolerated dose (MTD) in a homogenous patient population with advanced metastatic colorectal cancer (mCRC) and wild-type Kirsten rat sarcoma (KRAS). Part B will be initiated when a safe dose has been established in Part A. If MTD equals 12 mg/kg, then part C will explore the 9 mg/kg level. Part D and E is to validate the safety, PK and efficacy when administered every 2 weeks at doses of 12 mg/kg and 18 mg/kg, respectively. Part F is to validate safety, PK and efficacy when administered with a single loading dose of 9 mg/kg followed by weekly doses of 6 mg/kg.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients with refractory or recurrent advanced late stage solid tumors without available therapeutic options .
- •Part B, C, D, E and F:
- •Patients with refractory or recurrent advanced mCRC and wild-type KRAS who have progressed on epidermal growth factor receptor (EGFR) Ab treatment.
- •Patients wit confirmed response while on treatment anti-EGFR Ab treatment.
- •Documented disease progression during or within 6 months after cessation of anti-EGFR Ab treatment.
- •Patients must be willing to have a biopsy performed from a tumor lesion at screening and at Visit
- •Part A, B, C, D, E and F:
- •Histologically or cytologically confirmed diagnosis of cancer
- •Failure and/or intolerance to standard chemotherapy
- •Life expectancy of at least 3 months
Exclusion Criteria
- •Patients with clinically symptomatic brain metastases.
- •Received the following treatments prior to Visit 2:
- •Cytotoxic or cytostatic anti-cancer chemotherapy within 4 weeks
- •Total resection or irradiation of the target lesion
- •Antibody therapy within 4 weeks and vaccines within 12 weeks
- •Tyrosin kinase inhibitors within 4 weeks
- •Any investigational agent within 4 weeks
- •Diarrhea CTCAE \>1
- •Skin rash CTCAE \>1
- •Abnormal organ or bone marrow function.
Arms & Interventions
Sym004
Intervention: Sym004
Outcomes
Primary Outcomes
Number of Participants With Adverse Events (AEs)
Time Frame: Visit 2 until first follow-up visit (up to 66 weeks)
The AEs were used as a primary endpoint. AEs were summarized using descriptive statistics and presented overall by system organ class and preferred term. The frequencies of AEs were presented including number and percentages of participants with events and the total number of events.
Secondary Outcomes
- Antitumor Activity(Up to 62 weeks)
- Antitumor Activity Endpoints - Time-to-event Endpoints(Up to 62 weeks)
- Terminal Half-Life (T½)(See Time Frame in the Outcome Measure Description)