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
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Affimed GmbH
- 入组人数
- 112
- 试验地点
- 16
- 主要终点
- Phase 1: Incidence of Dose Limiting Toxicities (DLTs) During Cycle 1
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Expansion Phase
The expansion phase will collect preliminary evidence of efficacy and further confirm the safety of AFM24 in combination with atezolizumab.
干预措施: AFM24 (Drug)
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.
干预措施: Atezolizumab 840 MG in 14 ML Injection (Drug)
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.
干预措施: AFM24 (Drug)
Expansion Phase
The expansion phase will collect preliminary evidence of efficacy and further confirm the safety of AFM24 in combination with atezolizumab.
干预措施: Atezolizumab 840 MG in 14 ML Injection (Drug)
结局指标
主要结局
Phase 1: Incidence of Dose Limiting Toxicities (DLTs) During Cycle 1
时间窗: 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])
时间窗: 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.
次要结局
- Pharmacokinetics (PK) of AFM24(During cycle 1 (each cycle has 28 days))
- 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).)
- 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).)
- 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.)
- Phase 2a: Duration of Response(From the date of first response (unconfirmed) until progression disease assessed by investigator or death.)
- 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.)
- 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.)
- Phase 2a: Progression-free Survival(From the first treatment received until the first progression disease assessed by investigator or death.)
- 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.)