Clinical trial NCT05109442: Study to Assess AFM24 in Combination with Atezolizumab in Selected Advanced/Metastatic EGFR-expressing Cancers
Official title: A Phase 1/2a Open Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Efficacy of AFM24 in Combination with Atezolizumab in Patients with Selected Advanced/Metastatic EGFR-expressing Cancers
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Lead sponsor: Affimed GmbH
Sponsor class: INDUSTRY
First posted: 2021-11-05
Enrollment: 148
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: AFM24-102 is a Phase 1/2a open-label, non-randomized, multicenter, dose escalation, and expansion study evaluating AFM24 in combination with atezolizumab in patients with selected EGRF-expressing advanced solid malignancies whose disease has progressed after treatment with previous anticancer therapies.

Detailed description: There will be 2 parts in this study: a dose escalation phase (phase 1) and an expansion phase (phase 2a). Patients will qualify to receive the investigational drugs (AFM24 + atezolizumab) in the dose escalation phase or the expansion phase only if they are deemed eligible following the safety lead-in phase. Seven days before the planned first combination treatment, patients will receive a single dose of AFM24 and will be observed for any adverse events for 1 week.

The aim of the dose escalation phase is to determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of AFM24 in combination with atezolizumab.

The dose escalation phase will be followed by the expansion phase once the MTD/RP2D of AFM24 in combination with atezolizumab has been determined. The expansion phase of the study is intended to collect preliminary evidence of efficacy and to further confirm the safety of AFM24 in combination with atezolizumab.

The tumor types planned to be studied in the AFM24/atezolizumab combination study will be:

* Non-small cell lung cancer (EGFR-WT), with disease progression after chemotherapy and PD1/PD-L1 targeted therapy
* Gastric/GEJ cancer if intolerant to or with disease progression after standard platinum-based chemotherapy
* Pancreatic/hepatocellular/biliary tract cancer with disease progression after standard of care (SOC) therapy or if there is no appropriate SOC available for their condition
* Advanced or metastatic NSCLC harboring a targetable EGFR kinase domain mutation with disease progression on or after received ≥1 prior lines of treatment for advanced disease, including a Tyrosine-Kinase Inhibitor (TKI) for EGFR mutations

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed advanced or metastatic EGFR-positive selected cancer types (except for NSCLC)
* Advanced or metastatic NSCLC, EGFR WT: disease has progressed after ≥ 1 prior lines of therapy which must have included a platinum-based doublet in combination with PD1/PD-L1 antibody or must have received an anti-PD1/PD-L1 antibody prior to or after a platinum-based doublet
* Advanced, unresectable, or metastatic gastric/GEJ adenocarinoma: after ≥ 1 prior chemotherapy regimen including a platinum and fluoropyrimidine doublet
* Advanced or metastatic HCC (BCLC C or B not amenable or refractory to locoregional therapy), hepatobiliary-, or pancreatic adenocarcinoma: after ≥1 prior line of an approved SOC therapy for the respective disease type or to whom the available SOC is not appropriate in the opinion of the investigator
* Advanced or metastatic NSCLC harboring a targetable EGFR kinase domain mutation and whose disease has progressed on or after having received ≥ prior TKI approved for EGFR mutated NSCLC. Subjects trated with a 1st or 2nd generation TKI in 1st line who developed a documented T790M mutation must have received a TKI targeting this mutation such as Osimertinib or Lazertinib to be eligible. Subjects must have documentation of EGFR mutated NSCLC as assessed by an approved test using genomic sequencing of tumor or circulation free tumor DNA. The patients should have received a 2nd line of treatment if approved and available or may be enrolled in the study if in the opinion of the investigator it is in the patient's best interest,or the SOC is not appropriate.
* Adequate organ function
* Phase 1: Evaluable or measurable disease per RECIST v1.1
* Phase 2a: Measurable disease per RECIST v1.1

Exclusion Criteria:

* Treatment with systemic anticancer therapy including investigational agent within 4 weeks of the first dose of study drug, 6 weeks for mitomycin C or nitrosoureas, 2 weeks (or 5 half-lives whichever is longer) for using fluorouracil or small molecule targeted drugs, 2 weeks for using traditional Chinese medicine with anti-tumor indication.
* 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 active in any other clinical study, or administration of other investigational agent

Primary outcomes:
measure: Phase 1: Incidence of dose limiting toxicities (DLTs) during Cycle 1
timeFrame: During cycle 1 (each cycle has 28 days)
measure: Phase 2a: Overall Response Rate (complete response [CR] + partial response [PR])
timeFrame: through study completion (estimated up to 36 weeks)
Secondary outcomes:
measure: Incidence of TEAEs and SAEs
timeFrame: through study completion (estimated up to 36 weeks)
measure: Pharmacokinetics (PK) of AFM24
timeFrame: During cycle 1 (each cycle has 28 days)
measure: Pharmacokinetics (PK) of AFM24
timeFrame: During cycle 1 (each cycle has 28 days)
measure: Pharmacokinetics (PK) of AFM24
timeFrame: During cycle 1 (each cycle has 28 days)
measure: Pharmacokinetics (PK) of AFM24
timeFrame: During cycle 1 (each cycle has 28 days)
measure: Frequency of patients developing anti-drug antibodies (ADAs) against AFM24
timeFrame: through study completion (estimated up to 36 weeks)
measure: Phase 1: Overall Response Rate (complete response [CR] + partial response [PR])
timeFrame: through study completion (estimated up to 36 weeks)
measure: Phase 2a: Progression-free survival
timeFrame: through study completion (estimated up to 36 weeks)
measure: Phase 2a: Duration of response
timeFrame: through study completion (estimated up to 36 weeks)
measure: Phase 2a: Clinical benefit rate (CR or PR [any duration] or stable disease equal or > 24 weeks)
timeFrame: through study completion (estimated up to 36 weeks)
measure: Phase 2a: Disease control rate (DCR) according to assessment
timeFrame: through study completion (estimated up to 36 weeks)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Suwon
country: Korea, Republic of
facility: The Catholic University of Korea St. Vincent's Hospital
city: Lublin
country: Poland
facility: Independent Public Teaching Hospital #4 in Lublin, Department of Clinical Oncology and Chemotherapy
city: Otwock
country: Poland
facility: European Health Center Otwock Fryderyk Chopin Hospital, Department of Clinical Oncology
city: Poznań
country: Poland
facility: MED-Polonia, Sp. z o.o. (LLC)
city: Słupsk
country: Poland
facility: Janusz Korczak Provincial Specialist Hospital in Slupsk Limited Liability Company
city: Warsaw
country: Poland
facility: Maria Sklodowska-Curie - National Research Institute of Oncology, Early Phase Research Department
city: Barcelona
country: Spain
facility: Vall d'Hebron Institute of Oncology (VHIO)
city: Madrid
country: Spain
facility: University Hospital Quiron Madrid
city: Pamplona
country: Spain
facility: University Clinic of Navarra - Pamplona
city: Valencia
country: Spain
facility: Hospital Clinic Universitario Biomedical Research institute INCLIVA
city: Sutton
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust - ICR
Study officials:
affiliation: Affimed GmbH
name: Daniela Morales-Espinosa, MD
role: STUDY_DIRECTOR
References: