Clinical trial NCT04259450: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Lead sponsor: Affimed GmbH
Sponsor class: INDUSTRY
First posted: 2020-02-06
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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.

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 SOC chemotherapy, VEGF(R) and EGFR targeted antibodies

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 (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.

Primary outcomes:
measure: Phase 1: The Number of Subjects With Dose Limiting Toxicities (DLTs) During Cycle 1
timeFrame: During Cycle 1 (up to 28 days)
measure: Phase 2a: Overall Response Rate (Complete Response [CR] + Partial Response [PR])
timeFrame: Up to approximately 16 weeks.
Secondary outcomes:
measure: Phase 1: The Number of Subjects With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From the start of first infusion till the last infusion + 30 days, up to approximately 43 weeks.
measure: Phase 1: The Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: From the start of first infusion till the last infusion + 30 days, up to approximately 43 weeks.
measure: Phase 1: Area Under the Concentration-time Curve From Time 0 to Time Tau (7 Days) of AFM24 in Plasma
timeFrame: Pre-dose (2 hours maximum) and 15, 30, 45 min after start of infusion (SOI) and end of infusion (EOI) and 1, 4, 18, 24, 48, 144 hours after EOI on Cycle 1 Day 22.
measure: Phase 1: Maximum Plasma Concentration (Cmax) of AFM24
timeFrame: Pre-dose (2 hours maximum) and 15, 30, 45 min after start of infusion (SOI) and end of infusion (EOI) and 1, 4, 18, 24, 48, 144 hours after EOI on Cycle 1 Day 1 and on pre-dose (2 hours maximum) Cycle 1 Day 8.
measure: Phase 1: Time of Maximum Observed Concentration (Tmax) of AFM24
timeFrame: Pre-dose (2 hours maximum) and 15, 30, 45 min after start of infusion (SOI) and end of infusion (EOI) and 1, 4, 18, 24, 48, 144 hours after EOI on Cycle 1 Day 22.
measure: Phase 1: Minimum Plasma Concentration (Cmin) of AFM24
timeFrame: Pre-dose (2 hours maximum) and 15, 30, 45 min after start of infusion (SOI) and end of infusion (EOI) and 1, 4, 18, 24, 48, 144 hours after EOI on Cycle 1 Day 1 and on pre-dose (2 hours maximum) Cycle 1 Day 22.
measure: Phase 1: The Number of Subjects Who Developed Anti-drug Antibodies (ADAs) and Neutralizing ADAs During Treatment With AFM24
timeFrame: Pre-dose cycle 1 Day 1 and end of treatment, up to approximately 39 weeks.
measure: Phase 1: Overall Response Rate (Complete Response (CR) + Partial Response (PR))
timeFrame: From the start of first infusion till the last infusion + 30 days, up to approximately 43 weeks.
measure: Phase 1: Duration of Response Rate (DOR)
timeFrame: through study completion (estimated up to 24 weeks)
measure: Phase 1: Disease Control Rate (Complete Response (CR) + Partial Response (PR) +Stable Disease (SD))
timeFrame: From the start of first infusion till the last infusion + 30 days, up to approximately 43 weeks.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Boston
country: United States
facility: Dana Faber Cancer Institute
state: Massachusetts
city: Frankfurt am Main
country: Germany
facility: Nordwest Hospital GmbH
state: Hessen
city: Essen
country: Germany
facility: University Duisburg-Essen, University Hospital Essen
city: Hamburg
country: Germany
facility: University Hospital Hamburg-Eppendorf
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Suwon
country: Korea, Republic of
facility: The Catholic University of Korea St. Vincent's Hospital
city: Barcelona
country: Spain
facility: Vall d'Hebron Institute of Oncology
city: Madrid
country: Spain
facility: University Hospital Foundation Jimenez Diaz
city: Madrid
country: Spain
facility: University Hospital HM Sanchinarro
city: Valencia
country: Spain
facility: Hospital Clinic Universitario Biomedical Research institute INCLIVA
city: London
country: United Kingdom
facility: Institute of Cancer Research - Royal Marsden
Study officials:
affiliation: Affimed GmbH
name: Michael Emig, MD
role: STUDY_DIRECTOR
References: