Study to Assess AFM24 in Advanced Solid Cancers

NCT ID: NCT04259450

Last Updated: 2025-07-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 85 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-07
• Study Completion Date: 2024-06-24

Brief Summary

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.

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

Conditions

Advanced Solid Tumor

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

14 mg AFM24

Intervention Type: DRUG

14 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.

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.

Group Type: EXPERIMENTAL

40 mg AFM24

Intervention Type: DRUG

40 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.

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.

Group Type: EXPERIMENTAL

80 mg AFM24

Intervention Type: DRUG

80 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.

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.

Group Type: EXPERIMENTAL

160 mg AFM24

Intervention Type: DRUG

160 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.

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.

Group Type: EXPERIMENTAL

320 mg AFM24

Intervention Type: DRUG

320 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.

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.

Group Type: EXPERIMENTAL

480 mg AFM24

Intervention Type: DRUG

480 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.

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).

Group Type: EXPERIMENTAL

720 mg AFM24

Intervention Type: DRUG

720 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.

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).

Group Type: EXPERIMENTAL

480 mg AFM24

Intervention Type: DRUG

480 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.

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).

Group Type: EXPERIMENTAL

480 mg AFM24

Intervention Type: DRUG

480 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.

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).

Group Type: EXPERIMENTAL

480 mg AFM24

Intervention Type: DRUG

480 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.

Interventions

14 mg AFM24

14 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.

Intervention Type: DRUG

40 mg AFM24

40 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.

Intervention Type: DRUG

80 mg AFM24

80 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.

Intervention Type: DRUG

160 mg AFM24

160 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.

Intervention Type: DRUG

320 mg AFM24

320 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.

Intervention Type: DRUG

480 mg AFM24

480 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.

Intervention Type: DRUG

720 mg AFM24

720 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Affimed GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Emig, MD

Role: STUDY_DIRECTOR

Affimed GmbH

Locations

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

University Hospital HM Sanchinarro

Madrid, , Spain

Hospital Clinic Universitario Biomedical Research institute INCLIVA

Valencia, , Spain

Institute of Cancer Research - Royal Marsden

London, , United Kingdom

Countries

United States; Germany; South Korea; Spain; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

AFM24-101

Identifier Type: -

Identifier Source: org_study_id