This is an open-label, multi-center study to evaluate the safety, tolerability, and anti-tumor activity of SNK01 in combination with AFM24 in subjects with advanced or metastatic EGFR-expressing cancers.
The study will be conducted in two phases. The Phase 1/dose escalation phase will gather preliminary safety and tolerability data for escalating doses of AFM24 in combination with SNK01 at a fixed dose in order to determine the MTD/RP2D for the combination dose regimen to be used in the Phase 2a/expansion. The Phase 2a/expansion portion of the study will gather additional safety, tolerability, efficacy, and anti-tumor activity information for the combination of AFM24 with SNK01 in subjects with three types of advanced or metastatic EGFR-expressing cancers.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
11
USC/Norris Comprehensive Cancer Center
Los Angeles, California, United States
Sarcoma Oncology Center
Santa Monica, California, United States
University of Chicago
Chicago, Illinois, United States
Phase 1/Dose Escalation
Determine the maximum tolerated dose (MTD) of AFM24 in combination with SNK01. To be assessed by the incidence and severity of dose-limiting toxicity (DLT) within the DLT observation period.
Time frame: 28 days starting on cycle 1 day 1
Phase 1/Dose Escalation
Determine the recommended phase 2 dose (RP2D) of AFM24 in combination with SNK01. To be assessed by the incidence and severity of dose-limiting toxicity (DLT) within the DLT observation period.
Time frame: 28 days starting on cycle 1 day 1
Phase 2a/Expansion
Determine objective response rate (ORR) of AFM24 in combination with SNK01. Determine ORR using Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1
Time frame: Up to 24 months
Phase 1/Dose Escalation
Assess safety and tolerability of AFM24 in combination with SNK01. Determine frequency and severity of treatment-emergent AEs (TEAEs) per National Cancer Institute's Common Toxicity Criteria for Adverse Events (NCI CTCAE v 5.0).
Time frame: Up to 24 months
Phase 1/Dose Escalation
Determine preliminary efficacy of AFM24 in combination with SNK01. Determine ORR using RECIST v1.1 evaluated by local assessment.
Time frame: Up to 24 months
Phase 1/Dose Escalation
Maximum observed plasma concentration (Cmax) of AFM24
Time frame: 28 days starting on cycle 1 day 1
Phase 1/Dose Escalation
Time to maximum plasma concentration (Tmax) of AFM24
Time frame: 28 days starting on cycle 1 day 1
Phase 1/Dose Escalation
Minimum plasma concentration (Cmin) of AFM24
Time frame: 28 days starting on cycle 1 day 1
Phase 1/Dose Escalation
Area under plasma concentration-time curve for dosing interval (AUCtau) of AFM24
Time frame: 28 days starting on cycle 1 day 1
Phase 1/Dose Escalation
Immunogenicity of AFM24 when AFM24 is given in combination with SNK01 Frequency of subjects developing AFM24 anti drug antibodies (ADAs) through completion of the Phase 1/dose escalation portion
Time frame: Up to 24 months
Phase 2a/Expansion
Safety and tolerability of AFM24 in combination with SNK01 Frequency of TEAEs graded according to NCI CTCAE v 5.0
Time frame: Up to 24 months
Phase 2a/Expansion
To assess progression-free survival (PFS) according to RECIST v1.1 by local assessment Assess the number of subjects with PFS defined as duration of time from start of combination treatment to date of progression.
Time frame: Up to 24 months
Phase 2a/Expansion
To assess overall survival (OS).
Time frame: Up to 24 months
Phase 2a/Expansion
To assess duration of response (DOR) according to RECIST v1.1 by local assessment.
Time frame: Up to 24 months
Phase 2a/Expansion
To assess clinical benefit rate (CBR) according to RECIST v1.1 by local assessment.
Time frame: Up to 24 months
Phase 2a/Expansion
Maximum observed plasma concentration (Cmax) of AFM24.
Time frame: 28 days starting on cycle 1 day 1
Phase 2a/Expansion
Time to maximum plasma concentration (Tmax) of AFM24.
Time frame: 28 days starting on cycle 1 day 1
Phase 2a/Expansion
Minimum plasma concentration (Cmin) of AFM24.
Time frame: 28 days starting on cycle 1 day 1
Phase 2a/Expansion
Area under plasma concentration-time curve for dosing interval (AUCtau) of AFM24.
Time frame: 28 days starting on cycle 1 day 1
Phase 2a/Expansion
Immunogenicity of AFM24 when AFM24 is given in combination with SNK01 Frequency of subjects developing AFM24 ADAs and frequency of subjects developing neutralizing ADAs.
Time frame: Up to 24 months
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