Clinical Trials /

Study to Assess AFM24 in Advanced Solid Cancers

NCT04259450

Description:

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. 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 4 arms based on tumor type of metastatic colorectal cancer and non-small cell lung cancer. 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.

Related Conditions:
  • Breast Carcinoma
  • Cervical Carcinoma
  • Colorectal Carcinoma
  • Esophageal Carcinoma
  • Gastric Carcinoma
  • Glioblastoma
  • Head and Neck Carcinoma
  • Kidney Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Pancreatic Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study to Assess AFM24 in Advanced Solid Cancers
  • 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 IDs

  • ORG STUDY ID: AFM24-101
  • NCT ID: NCT04259450

Conditions

  • Advanced Solid Tumor

Interventions

DrugSynonymsArms
AFM24AFM24

Purpose

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. 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 4 arms based on tumor type of metastatic colorectal cancer and non-small cell lung cancer. 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.

Trial Arms

NameTypeDescriptionInterventions
AFM24ExperimentalPhase 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.
  • AFM24

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically or cytologically confirmed advanced or metastatic solid malignancies
             that are known to express EGFR, or in which EGFR is thought to be a relevant
             therapeutic target, including but not limiting to: colorectal, lung, gastric,
             esophageal, pancreatic, head and neck, breast, ovarian, cervical, urothelial, and
             renal cancers, and Glioblastoma multiforme.

          -  Previously treated with one or more 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.

          -  Adequate organ function

          -  Patients must have at least one tumor site that is accessible to biopsy

          -  Phase 2a only: Measurable disease per RECIST v1.1

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1: Incidence of dose limiting toxicities (DLTs) during Cycle 1
Time Frame:During Cycle 1 (each cycle is 28 days)
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Pharmacokinetics (PK) of AFM24
Time Frame:During Cycle 1 (each cycle is 28 days)
Safety Issue:
Description:Maximum plasma concentration (Cmax)
Measure:Pharmacokinetics (PK) of AFM24
Time Frame:During Cycle 1 (each cycle is 28 days)
Safety Issue:
Description:Minimum plasma concentration (Cmin)
Measure:Pharmacokinetics (PK) of AFM24
Time Frame:During Cycle 1 (each cycle is 28 days)
Safety Issue:
Description:Area under the concentration-time curve (AUCss(0-t))
Measure:Pharmacokinetics (PK) of AFM24
Time Frame:During Cycle 1 (each cycle is 28 days)
Safety Issue:
Description:Clearance (CL)
Measure:Pharmacokinetics (PK) of AFM24
Time Frame:During Cycle 1 (each cycle is 28 days)
Safety Issue:
Description:Volume of Distribution (Vd) volume of Distribution at Steady state (Vss), terminal t1/2
Measure:Pharmacokinetics (PK) of AFM24
Time Frame:During Cycle 1 (each cycle is 28 days)
Safety Issue:
Description:Volume of Distribution at Steady state (Vss) terminal t1/2
Measure:Pharmacokinetics (PK) of AFM24
Time Frame:During Cycle 1 (each cycle is 28 days)
Safety Issue:
Description:Terminal half-life (t1/2)
Measure:Incidence of patients who develop anti-drug antibodies (ADAs) and neutralizing ADAs during treatment with AFM24
Time Frame:through study completion (estimated up to 24 weeks)
Safety Issue:
Description:Measurement of ADAs before and throughout treatment with AFM24
Measure:Overall Response Rate (complete response [CR] + partial response [PR])
Time Frame:through study completion (estimated up to 24 weeks)
Safety Issue:
Description:Assessed by: Local RECIST v1.1
Measure:Duration of Response Rate (DOR)
Time Frame:through study completion (estmated up to 24 weeks)
Safety Issue:
Description:Assessed by: Local RECIST v1.1
Measure:Disease Control rate (CR + PR +stable disease [SD])
Time Frame:through study completion (Estimated up to 24 weeks)
Safety Issue:
Description:Assessed by: Local RECIST v1.1
Measure:Phase 2a: Number of patients with drug-related Adverse Events (AEs) grade 3 or worse)
Time Frame:through study completion (Estimated up to 24 weeks)
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Affimed GmbH

Last Updated

February 5, 2020