Study to Assess AFM24 in Advanced Solid Cancers

• ClinicalTrials.gov Identifier: NCT04259450
• Recruitment Status: Active, not recruiting
• First Posted: February 6, 2020
• Last Update Posted: August 23, 2023
• Sponsor: Affimed GmbH
• Information provided by (Responsible Party): Affimed GmbH

Tracking Information

• First Submitted Date: February 3, 2020
• First Posted Date: February 6, 2020
• Last Update Posted Date: August 23, 2023
• Actual Study Start Date: April 7, 2020
• Actual Primary Completion Date: July 12, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 22, 2021)

• Phase 1: Incidence of dose limiting toxicities (DLTs) during Cycle 1 [ Time Frame: During Cycle 1 (each cycle is 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
• Phase 2a: Overall Response Rate (complete response [CR] + partial response [PR]) [ Time Frame: through study completion (estimated up to 24 weeks) ]
  Assessed by Local RECIST v1.1

Original Primary Outcome Measures (submitted: February 5, 2020)

• Phase 1: Incidence of dose limiting toxicities (DLTs) during Cycle 1 [ Time Frame: During Cycle 1 (each cycle is 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
• Phase 2a: Overall Response Rate (complete response [CR] + partial response [PR]) [ Time Frame: through study completion (estimated up to 24 weeks) ]
  Assessed by: Local RECIST v1.1

Current Secondary Outcome Measures (submitted: September 22, 2021)

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

Original Secondary Outcome Measures (submitted: February 5, 2020)

• Pharmacokinetics (PK) of AFM24 [ Time Frame: During Cycle 1 (each cycle is 28 days) ]
  Maximum plasma concentration (Cmax)
• Pharmacokinetics (PK) of AFM24 [ Time Frame: During Cycle 1 (each cycle is 28 days) ]
  Minimum plasma concentration (Cmin)
• Pharmacokinetics (PK) of AFM24 [ Time Frame: During Cycle 1 (each cycle is 28 days) ]
  Area under the concentration-time curve (AUCss(0-t))
• Pharmacokinetics (PK) of AFM24 [ Time Frame: During Cycle 1 (each cycle is 28 days) ]
  Clearance (CL)
• Pharmacokinetics (PK) of AFM24 [ Time Frame: During Cycle 1 (each cycle is 28 days) ]
  Volume of Distribution (Vd) volume of Distribution at Steady state (Vss), terminal t1/2
• Pharmacokinetics (PK) of AFM24 [ Time Frame: During Cycle 1 (each cycle is 28 days) ]
  Volume of Distribution at Steady state (Vss) terminal t1/2
• Pharmacokinetics (PK) of AFM24 [ Time Frame: During Cycle 1 (each cycle is 28 days) ]
  Terminal half-life (t1/2)
• 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) ]
  Measurement of ADAs before and throughout treatment with AFM24
• Overall Response Rate (complete response [CR] + partial response [PR]) [ Time Frame: through study completion (estimated up to 24 weeks) ]
  Assessed by: Local RECIST v1.1
• Duration of Response Rate (DOR) [ Time Frame: through study completion (estmated up to 24 weeks) ]
  Assessed by: Local RECIST v1.1
• Disease Control rate (CR + PR +stable disease [SD]) [ Time Frame: through study completion (Estimated up to 24 weeks) ]
  Assessed by: Local RECIST v1.1
• 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) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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

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 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

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

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Solid Tumor

Intervention

Drug: AFM24

intravenous infusions

Study Arms

Experimental: AFM24

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.

Intervention: Drug: AFM24

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: August 22, 2023): 85
• Original Estimated Enrollment (submitted: February 5, 2020): 70
• Estimated Study Completion Date: December 31, 2024
• Actual Primary Completion Date: July 12, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany, Korea, Republic of, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04259450
• Other Study ID Numbers: AFM24-101
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Affimed GmbH
• Original Responsible Party: Same as current
• Current Study Sponsor: Affimed GmbH
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Michael Emig, MD; Affimed GmbH

• PRS Account: Affimed GmbH
• Verification Date: August 2023