Study to Assess AFM24 in Advanced Solid Cancers

Affimed

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Advanced Solid Tumor

Treatments: Drug: 480 mg AFM24; Drug: 320 mg AFM24; Drug: 720 mg AFM24; Drug: 80 mg AFM24; Drug: 14 mg AFM24; Drug: 160 mg AFM24; Drug: 40 mg AFM24

Study type: Interventional

Funder types: Industry

Identifiers

NCT04259450

AFM24-101

Details and patient eligibility

About

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.

Full 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

Enrollment: 85 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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85 participants in 10 patient groups

Phase 1- 14 mg Cohort 1

Experimental group

Description:

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.

Treatment:

Drug: 14 mg AFM24

Phase 1- 40 mg Cohort 2

Experimental group

Description:

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.

Treatment:

Drug: 40 mg AFM24

Phase 1- 80 mg Cohort 3

Experimental group

Description:

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.

Treatment:

Drug: 80 mg AFM24

Phase 1- 160 mg Cohort 4

Experimental group

Description:

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.

Treatment:

Drug: 160 mg AFM24

Phase 1- 320 mg Cohort 5

Experimental group

Description:

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.

Treatment:

Drug: 320 mg AFM24

Phase 1- 480 mg Cohort 6

Experimental group

Description:

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.

Treatment:

Drug: 480 mg AFM24

Phase 1- 720 mg Cohort 7

Experimental group

Description:

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).

Treatment:

Drug: 720 mg AFM24

Phase 2- CRC 480 mg Cohort A

Experimental group

Description:

Subjects with microsatellite stable (MSS) colorectal cancer (CRC) with rat sarcoma gene (RAS) wild-type tumor expressing EGFR 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).

Treatment:

Drug: 480 mg AFM24

Phase 2- ccRCC 480 mg Cohort B

Experimental group

Description:

Subjects with clear cell renal cell carcinoma (ccRCC) expressing EGFR 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).

Treatment:

Drug: 480 mg AFM24

Phase 2- NSCLC 480 mg Cohort C

Experimental group

Description:

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).

Treatment:

Drug: 480 mg AFM24