Study to Assess AFM24 in Advanced Solid Cancers

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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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

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: AFM24


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AFM24<br>Phase 1: Treatment of escalating doses of AFM24. Phase 2a: Treatment of AFM24 at maximum tolerated dose/recommended phase 2 dose, stratified into cohorts by tumor type. | Drug: AFM24<br>* intravenous infusions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) of AFM24 | Maximum plasma concentration (Cmax) | During Cycle 1 (each cycle is 28 days) | 
| Pharmacokinetics (PK) of AFM24 | Minimum plasma concentration (Cmin) | During Cycle 1 (each cycle is 28 days) | 
| Pharmacokinetics (PK) of AFM24 | Area under the concentration-time curve over the dose interval (AUCtau) | During Cycle 1 (each cycle is 28 days) | 
| Pharmacokinetics (PK) of AFM24 | Time to Cmax (Tmax) | During Cycle 1 (each cycle is 28 days) | 
| 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) | 
| Overall Response Rate (complete response [CR] + partial response [PR]) | Assessed by Local RECIST v1.1 | through study completion (estimated up to 24 weeks) | 
| Duration of Response Rate (DOR) | Assessed by: Local RECIST v1.1 | through study completion (estmated up to 24 weeks) | 
| Disease Control rate (CR + PR +stable disease [SD]) | Assessed by: Local RECIST v1.1 | through study completion (Estimated up to 24 weeks) | 
| Incidence of patients with treatment-emergent adverse events (TEAEs) and serious adverse events |  | through study completion (Estimated up to 24 weeks) |