Study to Assess AFM24 in Advanced Solid Cancers

NCT04259450 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: AFM24-101
• Study Type: interventional
• Target: 85
• Locations: 5 countries
• Sites: 13

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.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (21)

• Phase 1: The Number of Subjects With Treatment-emergent Adverse Events (TEAEs)

  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)

  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

  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

  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

  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.

Study Arms (10)

Phase 1- 14 mg Cohort 1

EXPERIMENTAL

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

Phase 1- 40 mg Cohort 2

EXPERIMENTAL

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

Phase 1- 80 mg Cohort 3

EXPERIMENTAL

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

Phase 1- 160 mg Cohort 4

EXPERIMENTAL

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

Phase 1- 320 mg Cohort 5

EXPERIMENTAL

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

Phase 1- 480 mg Cohort 6

EXPERIMENTAL

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

Phase 1- 720 mg Cohort 7

EXPERIMENTAL

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

Phase 2- CRC 480 mg Cohort A

EXPERIMENTAL

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

Phase 2- ccRCC 480 mg Cohort B

EXPERIMENTAL

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

Phase 2- NSCLC 480 mg Cohort C

EXPERIMENTAL

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

Interventions

14 mg AFM24 DRUG

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

Phase 1- 14 mg Cohort 1

40 mg AFM24 DRUG

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

Phase 1- 40 mg Cohort 2

80 mg AFM24 DRUG

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

Phase 1- 80 mg Cohort 3

160 mg AFM24 DRUG

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

Phase 1- 160 mg Cohort 4

320 mg AFM24 DRUG

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

Phase 1- 320 mg Cohort 5

480 mg AFM24 DRUG

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

Phase 1- 480 mg Cohort 6; Phase 2- CRC 480 mg Cohort A; Phase 2- NSCLC 480 mg Cohort C; Phase 2- ccRCC 480 mg Cohort B

720 mg AFM24 DRUG

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

Phase 1- 720 mg Cohort 7

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Affimed GmbH: lead

Study Sites (13)

University of Southern California

Los Angeles, California, 90033, United States

Location

Dana Faber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Nordwest Hospital GmbH

Frankfurt am Main, Hesse, 60488, Germany

Location

University Duisburg-Essen, University Hospital Essen

Essen, 45147, Germany

Location

University Hospital Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Seoul National University Bundang Hospital

Seongnam-si, 13620, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

The Catholic University of Korea St. Vincent's Hospital

Suwon, South Korea

Location

Vall d'Hebron Institute of Oncology

Barcelona, 08035, Spain

Location

University Hospital Foundation Jimenez Diaz

Madrid, 28040, Spain

Location

University Hospital HM Sanchinarro

Madrid, 28050, Spain

Location

Hospital Clinic Universitario Biomedical Research institute INCLIVA

Valencia, 46010, Spain

Location

Institute of Cancer Research - Royal Marsden

London, United Kingdom

Location

Limitations and Caveats

The central review of scans was terminated prematurely.

Results Point of Contact

• Title: Clinical Operations
• Organization: Affimed GmbH

trials@affimed.com

+49 62216530770

Study Officials

• Michael Emig, MD

  Affimed GmbH

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2020
• First Posted: February 6, 2020
• Study Start: April 7, 2020
• Primary Completion: July 12, 2023
• Study Completion: June 24, 2024
• Last Updated: July 17, 2025
• Results First Posted: August 29, 2024

Record last verified: 2025-06

Locations

US (2); ES (4); DE (3); KR (3); GB (1)