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

• ClinicalTrials.gov Identifier: NCT05109442
• Recruitment Status: Recruiting
• First Posted: November 5, 2021
• Last Update Posted: May 3, 2023
• Sponsor: Affimed GmbH
• Information provided by (Responsible Party): Affimed GmbH

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Advanced Solid Tumor	Drug: AFM24; Drug: Atezolizumab 840 MG in 14 ML Injection	Phase 1; Phase 2

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 105 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: November 19, 2021
• Estimated Primary Completion Date: September 30, 2024
• Estimated Study Completion Date: June 30, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Escalation Phase; 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.	Drug: AFM24; intravenous infusion; Drug: Atezolizumab 840 MG in 14 ML Injection; intravenous infusion
Experimental: Expansion Phase; The expansion phase will collect preliminary evidence of efficacy and further confirm the safety of AFM24 in combination with atezolizumab.	Drug: AFM24; intravenous infusion; Drug: Atezolizumab 840 MG in 14 ML Injection; intravenous infusion

Outcome Measures

Primary Outcome Measures :

1. Phase 1: Incidence of dose limiting toxicities (DLTs) during Cycle 1 [ Time Frame: 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
2. Phase 2a: Overall Response Rate (complete response [CR] + partial response [PR]) [ Time Frame: through study completion (estimated up to 36 weeks) ]
   RECIST v1.1 by investigator assessment

Secondary Outcome Measures :

1. Incidence of TEAEs and SAEs [ Time Frame: through study completion (estimated up to 36 weeks) ]
   Incidence of patients with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
2. Pharmacokinetics (PK) of AFM24 [ Time Frame: During cycle 1 (each cycle has 28 days) ]
   Maximum plasma concentration (Cmax)
3. Pharmacokinetics (PK) of AFM24 [ Time Frame: During cycle 1 (each cycle has 28 days) ]
   Minimum plasma concentration (Cmin)
4. Pharmacokinetics (PK) of AFM24 [ Time Frame: During cycle 1 (each cycle has 28 days) ]
   Area under the concentration-time curve over the dose interval (AUCtau)
5. Pharmacokinetics (PK) of AFM24 [ Time Frame: During cycle 1 (each cycle has 28 days) ]
   Time to Cmax (Tmax)
6. Frequency of patients developing anti-drug antibodies (ADAs) against AFM24 [ Time Frame: through study completion (estimated up to 36 weeks) ]
   Measurement of ADAs before and during treatment with AFM24 in combination with atezolizumab
7. Phase 1: Overall Response Rate (complete response [CR] + partial response [PR]) [ Time Frame: through study completion (estimated up to 36 weeks) ]
   RECIST v1.1 by investigator assessment
8. Phase 2a: Progression-free survival [ Time Frame: through study completion (estimated up to 36 weeks) ]
   RECIST v1.1 by investigator assessment
9. Phase 2a: Duration of response [ Time Frame: through study completion (estimated up to 36 weeks) ]
   RECIST v1.1 by investigator assessment
10. Phase 2a: Clinical benefit rate (CR or PR [any duration] or stable disease equal or > 24 weeks) [ Time Frame: through study completion (estimated up to 36 weeks) ]
    RECIST v1.1 by investigator assessment

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed advanced or metastatic EGFR-positive selected cancer types:
• 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
• 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

Contacts and Locations

Contacts

Contact: Affimed GmbH; 04962216743 ext 60; trials@affimed.com

Locations

United States, California

USC Norris Comprehensive Cancer Center; Recruiting

Los Angeles, California, United States, 90033

Contact: Anthony El-Khoueiry, MD

United States, Illinois

University of Chicago Medical Center; Recruiting

Chicago, Illinois, United States, 60637

Contact: Marina Garassino, MD

United States, Maryland

Johns Hopkins University; Recruiting

Baltimore, Maryland, United States, 21287

Contact: Eric Christenson, MD

Contact: Danielle Wendler phase1trials@jhmi.edu

Poland

European Health Center Otwock Fryderyk Chopin Hospital, Department of Clinical Oncology; Recruiting

Otwock, Poland, 05-400

Contact: Caezary Szczylik, MD

MED-Polonia, Sp. z o.o. (LLC); Active, not recruiting

Poznań, Poland, 60-693

Janusz Korczak Provincial Specialist Hospital in Slupsk Limited Liability Company; Active, not recruiting

Słupsk, Poland, 76-200

Maria Sklodowska-Curie - National Research Institute of Oncology, Early Phase Research Department; Active, not recruiting

Warsaw, Poland, 02-781

Spain

Vall d'Hebron Institute of Oncology (VHIO); Recruiting

Barcelona, Spain, 08035

Contact: Omar Saavedra, MD

Hospital Clinic Universitario Biomedical Research institute INCLIVA; Recruiting

Valencia, Spain, 46010

Contact: Andrés Cervantes, MD

United Kingdom

Royal Marsden NHS Foundation Trust - ICR; Recruiting

Sutton, United Kingdom, SM2 5PT

Contact: Juanita Lopez, MD

Sponsors and Collaborators

Affimed GmbH

Investigators

• Study Director: Daniela Morales-Espinosa, MD; Affimed GmbH

More Information

• Responsible Party: Affimed GmbH
• ClinicalTrials.gov Identifier: NCT05109442
• Other Study ID Numbers: AFM24-102
• First Posted: November 5, 2021
• Last Update Posted: May 3, 2023
• Last Verified: May 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Atezolizumab; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Immunological; Antineoplastic Agents