Study to Assess AFM24 in Advanced Solid Cancers

Phase 1

Completed

Conditions: Advanced Solid Tumor

Interventions: Drug: 480 mg AFM24
Drug: 14 mg AFM24
Drug: 40 mg AFM24
Drug: 160 mg AFM24
Drug: 320 mg AFM24
Drug: 80 mg AFM24
Drug: 720 mg AFM24

Registration Number: NCT04259450

Lead Sponsor: Affimed GmbH

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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 85

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase 2- ccRCC 480 mg Cohort B	480 mg AFM24	Subjects with clear cell renal cell carcinoma (ccRCC) expressing EGFR who recieved 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).
Phase 2- NSCLC 480 mg Cohort C	480 mg AFM24	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).
Phase 1- 14 mg Cohort 1	14 mg AFM24	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.
Phase 1- 40 mg Cohort 2	40 mg AFM24	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.
Phase 1- 160 mg Cohort 4	160 mg AFM24	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.
Phase 1- 480 mg Cohort 6	480 mg AFM24	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.
Phase 2- CRC 480 mg Cohort A	480 mg AFM24	Subjects with microsatellite stable (MSS) colorectal cancer (CRC) with rat sarcoma gene (RAS) wild-type tumor expressing EGFR who received 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).
Phase 1- 320 mg Cohort 5	320 mg AFM24	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.
Phase 1- 80 mg Cohort 3	80 mg AFM24	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.
Phase 1- 720 mg Cohort 7	720 mg AFM24	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).

Primary Outcome Measures

Name	Time	Method
Phase 1: The Number of Subjects With Dose Limiting Toxicities (DLTs) During Cycle 1	During Cycle 1 (up to 28 days)	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).
Phase 2a: Overall Response Rate (Complete Response [CR] + Partial Response [PR])	Up to approximately 16 weeks.	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.

Secondary Outcome Measures

Name	Time	Method
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.	Adverse Events (AEs) will be summarized with patient counts by Medical Dictionary for Regulatory Activities (MedDRA) System Organ Classes (SOCs) and Preferred Terms (PTs).
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.	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).
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.	Area under the concentration-time curve from time 0 to time tau (7 days) of AFM24 in plasma (AUC0-168)
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.	Maximum measured concentration (Cmax) of AFM24 in plasma
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.	First time to maximum observed concentration of AFM24 sampled during a dosing interval.
Phase 1: Minimum Plasma Concentration (Cmin) 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 22.	Minimum measured concentration (Cmin) of AFM24 in plasma
Phase 1: The Number of Subjects Who Developed Anti-drug Antibodies (ADAs) and Neutralizing ADAs During Treatment With AFM24	Pre-dose cycle 1 Day 1 and end of treatment, up to approximately 39 weeks.	The number of subjects who developed anti-drug antibodies (ADAs) at any time during the study.
Phase 1: Overall Response Rate (Complete Response (CR) + Partial Response (PR))	From the start of first infusion till the last infusion + 30 days, up to approximately 43 weeks.	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.
Phase 1: Disease Control Rate (Complete Response (CR) + Partial Response (PR) +Stable Disease (SD))	From the start of first infusion till the last infusion + 30 days, up to approximately 43 weeks.	Disease control at months 3, 6, and 9, as defined by achieving CR and/or PR and/or SD assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Phase 1: Duration of Response Rate (DOR)	through study completion (estimated up to 24 weeks)	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% CIs.

Trial Locations

Locations (13): Dana Faber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
University Duisburg-Essen, University Hospital Essen
🇩🇪
Essen, Germany
Nordwest Hospital GmbH
🇩🇪
Frankfurt am Main, Hessen, Germany
University of Southern California
🇺🇸
Los Angeles, California, United States
University Hospital Hamburg-Eppendorf
🇩🇪
Hamburg, Germany
Seoul National University Bundang Hospital
🇰🇷
Seongnam-si, Korea, Republic of
Samsung Medical Center
🇰🇷
Seoul, Korea, Republic of
The Catholic University of Korea St. Vincent's Hospital
🇰🇷
Suwon, Korea, Republic of
Vall d'Hebron Institute of Oncology
🇪🇸
Barcelona, Spain
University Hospital HM Sanchinarro
🇪🇸
Madrid, Spain
University Hospital Foundation Jimenez Diaz
🇪🇸
Madrid, Spain
Institute of Cancer Research - Royal Marsden
🇬🇧
London, United Kingdom
Hospital Clinic Universitario Biomedical Research institute INCLIVA
🇪🇸
Valencia, Spain