AFM24-101 is a first in human Phase 1/2a open-label, non-randomized, multi-center, multiple ascending dose escalation/expansion study evaluating AFM24 as monotherapy in patients with advanced solid malignancies whose disease has progressed after treatment with previous anticancer therapies. AFM24 is a tetravalent bispecific (anti-human EGFR x anti-human CD16A) innate immune cell engaging recombinant antibody being developed to target EGFR-expressing solid tumors and has been designed to specifically utilize the cytotoxic potential of the innate immune system, in particular natural killer cells and macrophages for the specific and efficient elimination of EGFR expressing cancer cells.
There will be two parts to this study: a dose escalation phase (1) and a dose expansion phase (2a). The aim of the dose escalation phase is to determine the maximum tolerated dose (MTD) and establish the recommended Phase 2a dose (RP2D). The dose escalation phase will be followed by the dose expansion phase once the MTD/RP2D of AFM24 monotherapy has been determined. The dose expansion phase of the study using the MTD/P2D is intended to collect preliminary evidence of efficacy and to further confirm the safety of AFM24 as a monotherapy. The expansion phase will have 3 arms based on tumor type. * Renal cell carcinoma(clear cell), failing standard of care (SoC) that includes TKIs and PD1 targeted therapy * Non-small cell lung cancer (EGFR-mut), failing SoC TKIs * Colorectal cancer, failing SOC chemotherapy, VEGF(R) and EGFR targeted antibodies
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
85
14 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.
40 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.
80 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.
160 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.
320 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.
480 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.
720 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.
University of Southern California
Los Angeles, California, United States
Dana Faber Cancer Institute
Boston, Massachusetts, United States
Nordwest Hospital GmbH
Frankfurt am Main, Hesse, Germany
University Duisburg-Essen, University Hospital Essen
Essen, Germany
University Hospital Hamburg-Eppendorf
Hamburg, Germany
Seoul National University Bundang Hospital
Seongnam-si, South Korea
Samsung Medical Center
Seoul, South Korea
The Catholic University of Korea St. Vincent's Hospital
Suwon, South Korea
Vall d'Hebron Institute of Oncology
Barcelona, Spain
University Hospital Foundation Jimenez Diaz
Madrid, Spain
...and 3 more locations
Phase 1: The Number of Subjects With Dose Limiting Toxicities (DLTs) During Cycle 1
The number of patients with dose limiting toxicities (DLTs) in the first cycle, as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0. DLT is defined as an adverse event (AE) or abnormal laboratory value assessed as unrelated to underlying disease, disease progression, inter-current illness, or concomitant medications, that occurs ≤28 days following the first dose of AFM24 (Cycle 1).
Time frame: During Cycle 1 (up to 28 days)
Phase 2a: Overall Response Rate (Complete Response [CR] + Partial Response [PR])
Overall response as defined by achieving confirmed CR and/or PR assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Partial or complete response needs to be confirmed with repeated assessment at least 4 weeks after the initial assessment.
Time frame: Up to approximately 16 weeks.
Phase 1: The Number of Subjects With Treatment-emergent Adverse Events (TEAEs)
Adverse Events (AEs) will be summarized with patient counts by Medical Dictionary for Regulatory Activities (MedDRA) System Organ Classes (SOCs) and Preferred Terms (PTs).
Time frame: From the start of first infusion till the last infusion + 30 days, up to approximately 43 weeks.
Phase 1: The Number of Subjects With Serious Adverse Events (SAEs)
Serious adverse Events (SAEs) will be summarized with patient counts by Medical Dictionary for Regulatory Activities (MedDRA) System Organ Classes (SOCs) and Preferred Terms (PTs).
Time frame: From the start of first infusion till the last infusion + 30 days, up to approximately 43 weeks.
Phase 1: Area Under the Concentration-time Curve From Time 0 to Time Tau (7 Days) of AFM24 in Plasma
Area under the concentration-time curve from time 0 to time tau (7 days) of AFM24 in plasma (AUC0-168)
Time frame: Pre-dose (2 hours maximum) and 15, 30, 45 min after start of infusion (SOI) and end of infusion (EOI) and 1, 4, 18, 24, 48, 144 hours after EOI on Cycle 1 Day 22.
Phase 1: Maximum Plasma Concentration (Cmax) of AFM24
Maximum measured concentration (Cmax) of AFM24 in plasma
Time frame: Pre-dose (2 hours maximum) and 15, 30, 45 min after start of infusion (SOI) and end of infusion (EOI) and 1, 4, 18, 24, 48, 144 hours after EOI on Cycle 1 Day 1 and on pre-dose (2 hours maximum) Cycle 1 Day 8.
Phase 1: Time of Maximum Observed Concentration (Tmax) of AFM24
First time to maximum observed concentration of AFM24 sampled during a dosing interval.
Time frame: Pre-dose (2 hours maximum) and 15, 30, 45 min after start of infusion (SOI) and end of infusion (EOI) and 1, 4, 18, 24, 48, 144 hours after EOI on Cycle 1 Day 22.
Phase 1: Minimum Plasma Concentration (Cmin) of AFM24
Minimum measured concentration (Cmin) of AFM24 in plasma
Time frame: Pre-dose (2 hours maximum) and 15, 30, 45 min after start of infusion (SOI) and end of infusion (EOI) and 1, 4, 18, 24, 48, 144 hours after EOI on Cycle 1 Day 1 and on pre-dose (2 hours maximum) Cycle 1 Day 22.
Phase 1: The Number of Subjects Who Developed Anti-drug Antibodies (ADAs) and Neutralizing ADAs During Treatment With AFM24
The number of subjects who developed anti-drug antibodies (ADAs) at any time during the study.
Time frame: Pre-dose cycle 1 Day 1 and end of treatment, up to approximately 39 weeks.
Phase 1: Overall Response Rate (Complete Response (CR) + Partial Response (PR))
Overall response as defined by achieving confirmed CR and/or PR assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Partial or complete response needs to be confirmed with repeated assessment at least 4 weeks after the initial assessment by local reader.
Time frame: From the start of first infusion till the last infusion + 30 days, up to approximately 43 weeks.
Phase 1: Duration of Response Rate (DOR)
The DOR defined as time from first assessment of partial response (PR) or complete response (CR) to follow-on first assessment of progressive disease will be summarized by descriptive statistics including median DOR and where appropriate the respective 95% confidence intervals (CIs).
Time frame: through study completion (estimated up to 24 weeks)
Phase 1: Disease Control Rate (Complete Response (CR) + Partial Response (PR) +Stable Disease (SD))
Disease control as defined by achieving CR and/or PR and/or SD assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Time frame: From the start of first infusion till the last infusion + 30 days, up to approximately 43 weeks.
Phase 2a: The Number of Subjects With Treatment-emergent Adverse Events (TEAEs)
Adverse Events (AEs) will be summarized with patient counts by Medical Dictionary for Regulatory Activities (MedDRA) System Organ Classes (SOCs) and Preferred Terms (PTs).
Time frame: From the start of first infusion till the last infusion + 30 days, up to approximately 105 weeks.
Phase 2a: The Number of Subjects With Serious Adverse Events (SAEs)
Serious adverse Events (SAEs) will be summarized with patient counts by Medical Dictionary for Regulatory Activities (MedDRA) System Organ Classes (SOCs) and Preferred Terms (PTs).
Time frame: From the start of first infusion till the last infusion + 30 days, up to approximately 105 weeks.
Phase 2a: Trough Concentration (Ctrough) of AFM24
Trough concentration (Ctrough) of AFM24 in plasma.
Time frame: Pre-dose (2 hours maximum) on Cycle 1 Day 22.
Phase 2a: Maximum Plasma Concentration (Cmax) of AFM24
Maximum measured concentration (Cmax) of AFM24 in plasma.
Time frame: Pre-dose (2 hours maximum) on Cycle 1 Day 22 and at end of infusion (EOI) on Cycle 1 Day 22.
Phase 2a: The Number of Subjects Who Developed Anti-drug Antibodies (ADAs) During Treatment With AFM24
The number of subjects who developed anti-drug antibodies (ADAs) at any time during the study.
Time frame: Pre-dose cycle 1 Day 1 and end of treatment, up to approximately 101 weeks.
Phase 2a: Overall Response Rate (Complete Response [CR] + Partial Response [PR]) Assessed by Central RECIST v1.1
Overall response as defined by achieving confirmed CR and/or PR assessed by Central Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Partial or complete response needs to be confirmed with repeated assessment at least 4 weeks after the initial assessment.
Time frame: From the start of first infusion till the last infusion + 30 days, up to approximately 105 weeks.
Phase 2a: Duration of Response Rate (DOR) by RECIST v1.1 by Local Review
The DOR defined as time from first assessment of partial response (PR) or complete response (CR) to follow-on first assessment of progressive disease will be summarized by descriptive statistics including median DOR and where appropriate the respective 95% confidence intervals (CIs). Assessments by local reader used only.
Time frame: From the start of first infusion till the last infusion + 30 days, up to approximately 105 weeks.
Phase 2a: Duration of Response Rate (DOR) by RECIST v1.1 by Central Review
The DOR defined as time from first assessment of partial response (PR) or complete response (CR) to follow-on first assessment of progressive disease will be summarized by descriptive statistics including median DOR and where appropriate the respective 95% confidence intervals (CIs). Assessment by central reader used only.
Time frame: From the start of first infusion till the last infusion + 30 days, up to approximately 105 weeks.
Phase 2a: Disease Control Rate (Complete Response (CR) + Partial Response (PR) +Stable Disease (SD))
Disease control as defined by achieving CR and/or PR and/or SD assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Disease control was assessed by local RECIST v1.1 and by central RECIST v1.1.
Time frame: From the start of first infusion till the last infusion + 30 days, up to approximately 105 weeks.
Phase 2a: Progression-free-survival (PFS)
Progression-Free Survival (PFS) was defined as (date of first progression - date of first study drug injection)/30.4375. PFS was measured by local and central assessments.
Time frame: From the start of first infusion till the last infusion + 30 days, up to approximately 105 weeks.
Phase 2a: Overall Survival
Overall Survival (OS) was defined as (date of death - date of first dose)/30.4375. Patients alive at the end of study will be censored on the last date of observation.
Time frame: From the start of first infusion till the last infusion + 30 days, up to approximately 105 weeks.
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