Study to Assess AFM24 in Advanced Solid Cancers

Advanced Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04259450
• Other study ID #: AFM24-101
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: April 7, 2020
• Est. completion date: December 31, 2024

Study information

• Verified date: August 2023
• Source: Affimed GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 construct 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-positive cancer cells.

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 chemotherapy plus EGFR targeted antibodies

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 85
• Est. completion date: December 31, 2024
• Est. primary completion date: July 12, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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, 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 (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.

Related Conditions & MeSH terms

• Advanced Solid Tumor

Intervention

Drug:
• AFM24
intravenous infusions

Locations

Country	Name	City	State
Germany	University Duisburg-Essen, University Hospital Essen	Essen
Germany	Nordwest Hospital GmbH	Frankfurt am Main	Hessen
Germany	University Hospital Hamburg-Eppendorf	Hamburg
Korea, Republic of	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
Spain	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
United Kingdom	Institute of Cancer Research - Royal Marsden	London
United States	Dana Faber Cancer Institute	Boston	Massachusetts
United States	University of Southern California	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Affimed GmbH

Countries where clinical trial is conducted

United States,  Germany,  Korea, Republic of,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1: Incidence of 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	During Cycle 1 (each cycle is 28 days)
Primary	Phase 2a: Overall Response Rate (complete response [CR] + partial response [PR])	Assessed by Local RECIST v1.1	through study completion (estimated up to 24 weeks)
Secondary	Pharmacokinetics (PK) of AFM24	Maximum plasma concentration (Cmax)	During Cycle 1 (each cycle is 28 days)
Secondary	Pharmacokinetics (PK) of AFM24	Minimum plasma concentration (Cmin)	During Cycle 1 (each cycle is 28 days)
Secondary	Pharmacokinetics (PK) of AFM24	Area under the concentration-time curve over the dose interval (AUCtau)	During Cycle 1 (each cycle is 28 days)
Secondary	Pharmacokinetics (PK) of AFM24	Time to Cmax (Tmax)	During Cycle 1 (each cycle is 28 days)
Secondary	Incidence of patients who develop anti-drug antibodies (ADAs) and neutralizing ADAs during treatment with AFM24	Measurement of ADAs before and throughout treatment with AFM24	through study completion (estimated up to 24 weeks)
Secondary	Overall Response Rate (complete response [CR] + partial response [PR])	Assessed by Local RECIST v1.1	through study completion (estimated up to 24 weeks)
Secondary	Duration of Response Rate (DOR)	Assessed by: Local RECIST v1.1	through study completion (estmated up to 24 weeks)
Secondary	Disease Control rate (CR + PR +stable disease [SD])	Assessed by: Local RECIST v1.1	through study completion (Estimated up to 24 weeks)
Secondary	Incidence of patients with treatment-emergent adverse events (TEAEs) and serious adverse events		through study completion (Estimated up to 24 weeks)