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

Study Overview
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Brief Summary
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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
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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

Official Title
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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

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: AFM24
* Drug: Atezolizumab 840 MG in 14 ML Injection


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Escalation Phase<br>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<br>* intravenous infusion<br>Drug: Atezolizumab 840 MG in 14 ML Injection<br>* intravenous infusion<br>|
| Experimental: Expansion Phase<br>The expansion phase will collect preliminary evidence of efficacy and further confirm the safety of AFM24 in combination with atezolizumab. | Drug: AFM24<br>* intravenous infusion<br>Drug: Atezolizumab 840 MG in 14 ML Injection<br>* intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| Pharmacokinetics (PK) of AFM24 | Maximum plasma concentration (Cmax) | During cycle 1 (each cycle has 28 days) | 
| Pharmacokinetics (PK) of AFM24 | Minimum plasma concentration (Cmin) | During cycle 1 (each cycle has 28 days) | 
| Pharmacokinetics (PK) of AFM24 | Area under the concentration-time curve over the dose interval (AUCtau) | During cycle 1 (each cycle has 28 days) | 
| Pharmacokinetics (PK) of AFM24 | Time to Cmax (Tmax) | During cycle 1 (each cycle has 28 days) | 
| 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) | 
| 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) | 
| Phase 2a: Progression-free survival | RECIST v1.1 by investigator assessment | through study completion (estimated up to 36 weeks) | 
| Phase 2a: Duration of response | RECIST v1.1 by investigator assessment | through study completion (estimated up to 36 weeks) | 
| 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) | 
| Phase 2a: Disease control rate (DCR) according to assessment | RECIST v1.1 by Investigator assessment | through study completion (estimated up to 36 weeks) |