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

Phase 1

Terminated

Conditions: Advanced Solid Tumor

Interventions: Drug: AFM24
Drug: Atezolizumab 840 MG in 14 ML Injection

Registration Number: NCT05109442

Lead Sponsor: Affimed GmbH

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

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 112

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 treated 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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Escalation Phase	AFM24	The Escalation phase will determine the MTD/RP2D of AFM24 in combination with atezolizumab. A traditional 3+3 design will be used to determine the RP2D.
Expansion Phase	AFM24	The expansion phase will collect preliminary evidence of efficacy and further confirm the safety of AFM24 in combination with atezolizumab.
Escalation Phase	Atezolizumab 840 MG in 14 ML Injection	The Escalation phase will determine the MTD/RP2D of AFM24 in combination with atezolizumab. A traditional 3+3 design will be used to determine the RP2D.
Expansion Phase	Atezolizumab 840 MG in 14 ML Injection	The expansion phase will collect preliminary evidence of efficacy and further confirm the safety of AFM24 in combination with atezolizumab.

Primary Outcome Measures

Name	Time	Method
Phase 1: Incidence of Dose Limiting Toxicities (DLTs) During Cycle 1	During cycle 1 (each cycle has 28 days)	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
Phase 2a: Overall Response Rate (Complete Response [CR] or Partial Response [PR])	Tumor assessments were conducted during last week of cycle 2, 4, 6, 8, 10, 12 and every 3 cycles thereafter (each cycle has 28 days), up to approximately 97 weeks.	Tumor assessment by RECIST v1.1 by investigator. Best overall response was used to define the Overall Response Rate (CR or PR). Best overall response is CR or PR if a CR or PR assessed at least 42 days after Cycle 1 Day 1 was confirmed by subsequent tumor assessment at least 4 weeks later.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics (PK) of AFM24	During cycle 1 (each cycle has 28 days)	Time to Cmax (Tmax) on Cycle 1 Day 22
Incidence of Patients With TEAEs	From first drug administration up to 30 (non-serious TEAEs) or 56 (serious TEAEs) days after last dose AFM24, until start of a subsequent anticancer treatment, or data cut-off date, whichever is sooner. Up to approx. 35 (phase 1) and 105 weeks (phase 2a).	Number of patients with treatment-emergent adverse events (TEAEs) non-serious or serious
Incidence of Patients With SAEs	From first drug administration up to 56 days after the last dose of AFM24, until the start of a subsequent anticancer treatment, or data cut-off date, whichever is sooner. Up to approximately 35 (phase 1) and 105 weeks (phase 2a).	Number of patients with treatment-emergent serious adverse events (serious TEAEs)
Frequency of Patients Developing Anti-drug Antibodies (ADAs) Against AFM24	Ph 1 within 2h prior to: each drug intake (Cycle 1), 1st + 3rd drug intake (Cycle 2 onwards) and at EOT, up to 27 weeks. Ph 2a within 2h prior to: 1st drug intake (Cycle 1 and Cycle 3 onwards), 1st + 3rd drug intake (Cycle 2) and at EOT, up to 97 weeks.	Measurement of ADAs before and during treatment with AFM24 in combination with atezolizumab Patients with at least one ADA-positive result at baseline or post-baseline counted as developing anti-drug antibodies (ADAs) against AFM24
Phase 2a: Duration of Response	From the date of first response (unconfirmed) until progression disease assessed by investigator or death.	Duration of Response (DOR) was defined as (date of first progression or death - date of first response (unconfirmed))/30.4375. Patients without response were excluded from the analysis. Patients without progression or death were censored. Tumor assessment by RECIST v1.1 by investigator.
Phase 2a: Disease Control Rate (DCR) (Complete Response [CR] or Partial Response [PR] or Stable Disease [SD])	Tumor assessments were conducted during last week of cycle 2, 4, 6, 8, 10, 12 and every 3 cycles thereafter (each cycle has 28 days), up to approximately 97 weeks.	Tumor assessment by RECIST v1.1 by investigator. Best overall response was used to define the Disease Control Rate (CR or PR or SD). Best overall response is CR or PR if a CR or PR assessed at least 42 days after Cycle 1 Day 1 was confirmed by subsequent tumor assessment at least 4 weeks later. Best overall response is SD if SD or unconfirmed CR or unconfirmed PR at least 42 days after C1D1.
Phase 1: Overall Response Rate (Complete Response [CR] or Partial Response [PR])	Tumor assessments were conducted during last week of cycle 2, 4, 6, 8, 10, 12 and every 3 cycles thereafter (each cycle has 28 days), up to approximately 27 weeks.	Tumor assessment by RECIST v1.1 by investigator. Best overall response was used to define the Overall Response Rate (CR or PR). Best overall response is CR or PR if a CR or PR assessed at least 42 days after Cycle 1 Day 1 was confirmed by subsequent tumor assessment at least 4 weeks later.
Phase 2a: Progression-free Survival	From the first treatment received until the first progression disease assessed by investigator or death.	Progression-Free Survival (PFS) was defined as (date of first progression - date of first study drug injection)/30.4375. Patients without progression or death were censored. Tumor assessment by RECIST v1.1 by investigator.
Phase 2a: Clinical Benefit Rate (CR or PR [Any Duration] or Stable Disease Equal or > 24 Weeks)	Tumor assessments were conducted during last week of cycle 2, 4, 6, 8, 10, 12 and every 3 cycles thereafter (each cycle has 28 days), up to approximately 97 weeks.	Tumor assessment by RECIST v1.1 by investigator. Best overall response was used to define the Clinical benefit rate (CR or PR or SD ≥24 weeks). Best overall response is CR or PR if a CR or PR assessed at least 42 days after Cycle 1 Day 1 was confirmed by subsequent tumor assessment at least 4 weeks later. Best overall response is SD if SD or unconfirmed CR or unconfirmed PR at least 42 days after C1D1. Best overall response SD counts for Clinical benefit rate if SD ongoing for at least 24 weeks.

Trial Locations

Locations (16): USC Norris Comprehensive Cancer Center
🇺🇸
Los Angeles, California, United States
University of Chicago Medical Center
🇺🇸
Chicago, Illinois, United States
Johns Hopkins University
🇺🇸
Baltimore, Maryland, United States
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, Korea, Republic of
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)
🇵🇱
Poznań, Poland
Janusz Korczak Provincial Specialist Hospital in Slupsk Limited Liability Company
🇵🇱
Słupsk, Poland
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USC Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Anthony El-Khoueiry, MD
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