Study to Assess AFM24 in Combination With Atezolizumab in Selected Advanced/Metastatic EGFR-expressing Cancers

Advanced Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05109442
• Other study ID #: AFM24-102
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 19, 2021
• Est. completion date: June 30, 2025

Study information

• Verified date: August 2023
• Source: Affimed GmbH
• Contact: Affimed GmbH
• Phone: +49 621 56003-0
• Email: trials[@]affimed.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 148
• Est. completion date: June 30, 2025
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumor

Intervention

Drug:
• AFM24
intravenous infusion
• Atezolizumab 840 MG in 14 ML Injection
intravenous infusion

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	The Catholic University of Korea St. Vincent's Hospital	Suwon
Poland	Independent Public Teaching Hospital #4 in Lublin, Department of Clinical Oncology and Chemotherapy	Lublin
Poland	European Health Center Otwock Fryderyk Chopin Hospital, Department of Clinical Oncology	Otwock
Poland	MED-Polonia, Sp. z o.o. (LLC)	Poznan
Poland	Janusz Korczak Provincial Specialist Hospital in Slupsk Limited Liability Company	Slupsk
Poland	Maria Sklodowska-Curie - National Research Institute of Oncology, Early Phase Research Department	Warsaw
Spain	Vall d'Hebron Institute of Oncology (VHIO)	Barcelona
Spain	University Hospital Quiron Madrid	Madrid
Spain	University Clinic of Navarra - Pamplona	Pamplona
Spain	Hospital Clinic Universitario Biomedical Research institute INCLIVA	Valencia
United Kingdom	Royal Marsden NHS Foundation Trust - ICR	Sutton
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Chicago Medical Center	Chicago	Illinois
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Affimed GmbH

Countries where clinical trial is conducted

United States,  Korea, Republic of,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1: Incidence of dose limiting toxicities (DLTs) during Cycle 1	The number of patients with dose limiting toxicities (DLTs) in the first cycle, as assessed by the National Cancer Institute Common Technology Criteria for Adverse Events (CTCAE) v5.0	During cycle 1 (each cycle has 28 days)
Primary	Phase 2a: Overall Response Rate (complete response [CR] + partial response [PR])	RECIST v1.1 by investigator assessment	through study completion (estimated up to 36 weeks)
Secondary	Incidence of TEAEs and SAEs	Incidence of patients with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)	through study completion (estimated up to 36 weeks)
Secondary	Pharmacokinetics (PK) of AFM24	Maximum plasma concentration (Cmax)	During cycle 1 (each cycle has 28 days)
Secondary	Pharmacokinetics (PK) of AFM24	Minimum plasma concentration (Cmin)	During cycle 1 (each cycle has 28 days)
Secondary	Pharmacokinetics (PK) of AFM24	Area under the concentration-time curve over the dose interval (AUCtau)	During cycle 1 (each cycle has 28 days)
Secondary	Pharmacokinetics (PK) of AFM24	Time to Cmax (Tmax)	During cycle 1 (each cycle has 28 days)
Secondary	Frequency of patients developing anti-drug antibodies (ADAs) against AFM24	Measurement of ADAs before and during treatment with AFM24 in combination with atezolizumab	through study completion (estimated up to 36 weeks)
Secondary	Phase 1: Overall Response Rate (complete response [CR] + partial response [PR])	RECIST v1.1 by investigator assessment	through study completion (estimated up to 36 weeks)
Secondary	Phase 2a: Progression-free survival	RECIST v1.1 by investigator assessment	through study completion (estimated up to 36 weeks)
Secondary	Phase 2a: Duration of response	RECIST v1.1 by investigator assessment	through study completion (estimated up to 36 weeks)
Secondary	Phase 2a: Clinical benefit rate (CR or PR [any duration] or stable disease equal or > 24 weeks)	RECIST v1.1 by investigator assessment	through study completion (estimated up to 36 weeks)
Secondary	Phase 2a: Disease control rate (DCR) according to assessment	RECIST v1.1 by Investigator assessment	through study completion (estimated up to 36 weeks)