Study to Assess AFM24 in Advanced Solid Cancers

A Phase 1/2a Open Label, Multicenter Study to Access the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of AFM24 in Patients With Advanced Solid Tumors

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.

Study Overview

• Status: Terminated
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: 14 mg AFM24; Drug: 40 mg AFM24; Drug: 80 mg AFM24; Drug: 160 mg AFM24; Drug: 320 mg AFM24; Drug: 480 mg AFM24; Drug: 720 mg AFM24

Detailed Description

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
• Enrollment (Actual): 85
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Germany
  • Essen, Germany, 45147
    • University Duisburg-Essen, University Hospital Essen
  • Hamburg, Germany, 20246
    • University Hospital Hamburg-Eppendorf
  • Hessen
    • Frankfurt am Main, Hessen, Germany, 60488
      • Nordwest Hospital GmbH
• Korea, Republic of
  • Seongnam-si, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Suwon, Korea, Republic of
    • The Catholic University Of Korea St. Vincent's Hospital
• Spain
  • Barcelona, Spain, 08035
    • Vall d'Hebron Institute of Oncology
  • Madrid, Spain, 28040
    • University Hospital Foundation Jimenez Diaz
  • Madrid, Spain, 28050
    • University Hospital HM Sanchinarro
  • Valencia, Spain, 46010
    • Hospital Clinic Universitario Biomedical Research institute INCLIVA
• United Kingdom
  • London, United Kingdom
    • Institute of Cancer Research - Royal Marsden
• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Faber Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adequate organ function
• Phase 1: Histologically or cytologically confirmed advanced or metastatic solid malignancies that are known to express EGFR
• Phase 1: Previously treated with ≥ 1 lines of anticancer therapy and have documented disease progression during or after their most recent line of anticancer therapy. In addition, either there is no further SOC therapy for the patient or the remaining SOC therapies are deemed not appropriate for the patient by the Investigator.
• Phase 1: Patients must have at least one tumor site that is accessible to biopsy
• Phase 2a: Measurable disease per RECIST 1.1
• Phase 2a: Histologically confirmed advanced or metastatic EGFR+ malignancies for each expansion cohorts:
• Colorectal Cancer (MSS), KRAS-wildtype: disease has progressed after ≥ 2 prior lines of therapy which must have included oxaliplatin, fluoropyrimidine, bevacizumab, and an anti-EGFR therapy
• ccRCC: disease has progressed after ≥ 2 prior lines of therapy which must have included a TKI and a checkpoint inhibitor
• metastatic NSCLC, EGFRmut: disease has progressed on/after after ≥ 1 prior lines of therapy for advanced disease including ≥ 1 prior TKI approved for EGFR mut NSCLC

Exclusion Criteria:

• Treatment with systemic anticancer therapy within 4 weeks of the first dose of study drug (6 weeks if therapy was mitomycin C and/or nitrosoureas), or within 5 half-lives of the agent if half-life is known and it is shorter, before first dose of study drug. Anticancer therapies include cytotoxic chemotherapy, targeted inhibitors, and immunotherapies, but do not include hormonal therapy or radiotherapy.
• Radiation therapy within 2 weeks before 1st dose of study drug or unresolved toxicity from previous radiotherapy.
• History of any other malignancy known to be active, with the exception of completely removed in situ cervical intra-epithelial neoplasia, non-melanoma skin cancer, DCIS, early stage prostate cancer that has been adequately treated, and other cancers from which the patient has been disease free for 3 years or longer.
• Currently participating in a study and receiving study therapy, or participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1- 14 mg Cohort 1; Subjects, with tumors known to express EGFR, who received 14 milligram (mg) AFM24 on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.	Drug: 14 mg AFM24; 14 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.
Experimental: Phase 1- 40 mg Cohort 2; Subjects, with tumors known to express EGFR, who received 40 milligram (mg) AFM24 on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.	Drug: 40 mg AFM24; 40 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.
Experimental: Phase 1- 80 mg Cohort 3; Subjects, with tumors known to express EGFR, who received 80 milligram (mg) AFM24 on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.	Drug: 80 mg AFM24; 80 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.
Experimental: Phase 1- 160 mg Cohort 4; Subjects, with tumors known to express EGFR, who received 160 milligram (mg) AFM24 on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.	Drug: 160 mg AFM24; 160 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.
Experimental: Phase 1- 320 mg Cohort 5; Subjects, with tumors known to express EGFR, who received 320 milligram (mg) AFM24 on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.	Drug: 320 mg AFM24; 320 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.
Experimental: Phase 1- 480 mg Cohort 6; Subjects, with tumors known to express EGFR, who received 480 milligram (mg) AFM24 on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.	Drug: 480 mg AFM24; 480 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.
Experimental: Phase 1- 720 mg Cohort 7; Subjects, with tumors known to express EGFR, who received 720 milligram (mg) AFM24 on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle. A dose could be given over two days (split day dosing).	Drug: 720 mg AFM24; 720 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.
Experimental: Phase 2- NSCLC 480 mg Cohort C; Subjects with advanced or metastatic (non-small cell lung cancer) NSCLC with an epidermal growth factor receptor (EGFR) mutation who received 480 milligram (mg) AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle. A dose could be given over two days (split day dosing).	Drug: 480 mg AFM24; 480 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.
Experimental: Phase 2- CRC 480 mg Cohort A; Subjects with microsatellite stable (MSS) colorectal cancer (CRC) with rat sarcoma gene (RAS) wild-type tumor expressing EGFR who received 480 milligram (mg) AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle. A dose could be given over two days (split day dosing).	Drug: 480 mg AFM24; 480 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.
Experimental: Phase 2- ccRCC 480 mg Cohort B; Subjects with clear cell renal cell carcinoma (ccRCC) expressing EGFR who received 480 milligram (mg) AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle. A dose could be given over two days (split day dosing).	Drug: 480 mg AFM24; 480 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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.	Up to approximately 16 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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).	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)	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	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.	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	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.	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.	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).	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.	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).	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).	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.	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.	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.	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.	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.	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.	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.	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.	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.	From the start of first infusion till the last infusion + 30 days, up to approximately 105 weeks.

Collaborators and Investigators

• Sponsor: Affimed GmbH
• Investigators: Study Director: Michael Emig, MD, Affimed GmbH

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2020
• Primary Completion (Actual): July 12, 2023
• Study Completion (Actual): June 24, 2024

Study Registration Dates

• First Submitted: February 3, 2020
• First Submitted That Met QC Criteria: February 5, 2020
• First Posted (Actual): February 6, 2020

Study Record Updates

• Last Update Posted (Actual): July 17, 2025
• Last Update Submitted That Met QC Criteria: June 30, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: AFM24-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No