Study to Assess AFM24 in Combination With Atezolizumab in Selected Advanced/Metastatic EGFR-expressing Cancers
Study Details
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 |
|---|---|---|
|
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:
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Non-small cell lung cancer (EGFR-WT), with disease progression after chemotherapy and PD1/PD-L1 targeted therapy
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Gastric/GEJ cancer if intolerant to or with disease progression after standard platinum-based chemotherapy
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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
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
- 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] + partial response [PR]) [through study completion (estimated up to 36 weeks)]
RECIST v1.1 by investigator assessment
Secondary Outcome Measures
- Incidence of TEAEs and SAEs [through study completion (estimated up to 36 weeks)]
Incidence of patients with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
- Pharmacokinetics (PK) of AFM24 [During cycle 1 (each cycle has 28 days)]
Maximum plasma concentration (Cmax)
- Pharmacokinetics (PK) of AFM24 [During cycle 1 (each cycle has 28 days)]
Minimum plasma concentration (Cmin)
- Pharmacokinetics (PK) of AFM24 [During cycle 1 (each cycle has 28 days)]
Area under the concentration-time curve over the dose interval (AUCtau)
- Pharmacokinetics (PK) of AFM24 [During cycle 1 (each cycle has 28 days)]
Time to Cmax (Tmax)
- Frequency of patients developing anti-drug antibodies (ADAs) against AFM24 [through study completion (estimated up to 36 weeks)]
Measurement of ADAs before and during treatment with AFM24 in combination with atezolizumab
- Phase 1: Overall Response Rate (complete response [CR] + partial response [PR]) [through study completion (estimated up to 36 weeks)]
RECIST v1.1 by investigator assessment
- Phase 2a: Progression-free survival [through study completion (estimated up to 36 weeks)]
RECIST v1.1 by investigator assessment
- Phase 2a: Duration of response [through study completion (estimated up to 36 weeks)]
RECIST v1.1 by investigator assessment
- Phase 2a: Clinical benefit rate (CR or PR [any duration] or stable disease equal or > 24 weeks) [through study completion (estimated up to 36 weeks)]
RECIST v1.1 by investigator assessment
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histologically or cytologically confirmed advanced or metastatic EGFR-positive selected cancer types:
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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
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Advanced, unresectable, or metastatic gastric/GEJ adenocarinoma: after ≥ 1 prior chemotherapy regimen including a platinum and fluoropyrimidine doublet
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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
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Adequate organ function
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Phase 1: Evaluable or measurable disease per RECIST v1.1
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Phase 2a: Measurable disease per RECIST v1.1
Exclusion Criteria:
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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.
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Radiation therapy within 2 weeks before 1st dose of study drug or unresolved toxicity from previous radiotherapy
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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
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Currently active in any other clinical study, or administration of other investigational agent
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | USC Norris Comprehensive Cancer Center | Los Angeles | California | United States | 90033 |
| 2 | Johns Hopkins University | Baltimore | Maryland | United States | 21287 |
| 3 | Vall d'Hebron Institute of Oncology (VHIO) | Barcelona | Spain | 08035 | |
| 4 | Hospital Clinic Universitario Biomedical Research institute INCLIVA | Valencia | Spain | 46010 | |
| 5 | Royal Marsden NHS Foundation Trust - ICR | Sutton | United Kingdom | SM2 5PT |
Sponsors and Collaborators
- Affimed GmbH
Investigators
- Study Director: Daniela Morales-Espinosa, MD, Affimed GmbH
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AFM24-102