Protocol ASPEN-09-03: A Single-arm Phase 2 Multicenter Study of Evorpacept in Combination With Trastuzumab and Chemotherapy in Participants With Metastatic HER2-Positive Breast Cancer, a Substudy Under Master Protocol ASPEN-09: A Phase 1b/2, Multicenter, Multi Arm Study of Evorpacept in Combination With Anti-cancer Therapies in Advanced / Metastatic Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 55
- 主要终点
- Overall Response Rate (ORR) using RECIST v1.1 based on BICR assessment
研究概览
简要总结
The Substudy Protocol ASPEN-09-03 is a Phase 2, single-arm, multicenter study evaluating the efficacy, safety, and tolerability of evorpacept in combination with trastuzumab and chemotherapy in participants with HER2-positive metastatic breast cancer who have previously received trastuzumab-deruxtecan. This substudy is actively recruiting.
ASPEN-09-03 is a substudy under Master Protocol ASPEN-09, and additional substudies are as follows:
- Metastatic colorectal cancer (CRC) - dose escalation phase to evaluate evorpacept in combination with other drugs. This substudy is not open.
- Recurrent/metastatic head and neck cancer (HNSCC) - dose escalation phase to evaluate evorpacept in combination with other drugs. This substudy is not open.
详细描述
Participants will continue study treatment until disease progression, death, unacceptable toxicity, participant request to stop treatment, investigator decision or study termination by the sponsor.
As ASPEN-09-03 (MBC) is the only substudy open under ASPEN-09, the information reflected in the enrollment number, arms/interventions, outcome measures, and eligibility criteria currently includes only MBC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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 confirmed invasive HER2+ breast cancer based on an evaluable tumor tissue biopsy obtained after cessation of T-DXd (ENHERTU) treatment and no more than 6 months prior to C1D
- •Received no more than 4 prior lines of HER2-directed therapy including at least one prior line of T-DXd (ENHERTU) for locally advanced/metastatic HER2+ breast cancer. Prior neoadjuvant therapy which resulted in relapse within 6 months of completion of T-DXd will be considered a line of treatment for metastatic disease. Participants who discontinue T-DXd due to intolerance are considered eligible.
- •Progressed on or following the most recent line of therapy.
- •Eligible to receive one of the following chemotherapy options (capecitabine, eribulin, gemcitabine, paclitaxel or vinorelbine).
- •Measurable disease as defined by RECIST v1.
- •LVEF ≥50%.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) must be 0 to
- •Life expectancy of at least 3 months.
- •Adequate renal function (estimated creatinine clearance ≥30 mL/min as calculated using the Cockcroft-Gault equation or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
- •Adequate liver function:
- •Total bilirubin ≤1.5 x upper limit of normal (ULN) (≤3.0 x ULN if the participant has documented Gilbert syndrome);
- •Aspartate and alanine transaminase (AST and ALT) ≤3 x ULN (≤5.0 x ULN if liver involved by metastatic disease).
- •Participants must have recovered from all AEs due to previous therapies, procedures, and surgeries to baseline severity or ≤Grade 1 per NCI CTCAE v5.0 except for AEs not deemed reversible and which do not constitute a safety risk by Investigator judgment.
排除标准
- •Untreated CNS metastases.
- •Prior exposure to any anti-CD47 or anti-SIRPα agent.
- •Any condition that would be contraindicated to receiving trastuzumab
- •Has a diagnosis of complete dihydropyrimidine dehydrogenase (DPD) deficiency or significant toxicity with prior flurouracil (5FU) based regimen
- •Following anti-cancer therapy with insufficient washout before start of treatment:
- •chemotherapy, hormonal therapy, radiation therapy or small molecule anti-cancer therapy within 14 days or 5 half-lives (whichever is shorter) of start of treatment.
- •Immune therapy or other biologic therapy (e.g., monoclonal antibodies, antibody-drug conjugates) for the treatment of cancer for: 28 days or 5 half-lives (whichever is shorter) of start of treatment).
- •History of autoimmune hemolytic anemia, autoimmune thrombocytopenia, or hemolytic transfusion reaction.
- •Had an allogeneic tissue/solid organ transplant.
- •Any active, unstable cardiovascular disease.
- •Intolerance to or who have had a severe allergic or anaphylactic reaction to antibodies or infused therapeutic proteins or participants who have had a severe allergic or anaphylactic reaction to any of the substances included in the study drug (including excipients).
- •Has an active autoimmune disease that has required systemic treatment in past 2 years.
- •Other primary malignancy within 2 years.
研究组 & 干预措施
Evorpacept+Trastuzumab+Chemo in participants with metastatic HER2+ breast cancer
-
Evorpacept (IV) - once every 3 weeks (Q3W)
-
Trastuzumab (IV) - once every 3 weeks (Q3W)
-
Chemotherapy (physician selects one of the following):
-
Capecitabine (Oral) twice a day for 14 days every 3 weeks
-
Eribulin (IV) twice every 3 weeks
-
Gemcitabine (IV) twice every 3 weeks
-
Paclitaxel (IV) once every 3 weeks (Q3W) or once weekly (QW)
-
Vinolrebine (IV) twice every 3 weeks
干预措施: Evorpacept (ALX148) (Drug)
Evorpacept+Trastuzumab+Chemo in participants with metastatic HER2+ breast cancer
-
Evorpacept (IV) - once every 3 weeks (Q3W)
-
Trastuzumab (IV) - once every 3 weeks (Q3W)
-
Chemotherapy (physician selects one of the following):
-
Capecitabine (Oral) twice a day for 14 days every 3 weeks
-
Eribulin (IV) twice every 3 weeks
-
Gemcitabine (IV) twice every 3 weeks
-
Paclitaxel (IV) once every 3 weeks (Q3W) or once weekly (QW)
-
Vinolrebine (IV) twice every 3 weeks
干预措施: Vinorelbine (Drug)
Evorpacept+Trastuzumab+Chemo in participants with metastatic HER2+ breast cancer
-
Evorpacept (IV) - once every 3 weeks (Q3W)
-
Trastuzumab (IV) - once every 3 weeks (Q3W)
-
Chemotherapy (physician selects one of the following):
-
Capecitabine (Oral) twice a day for 14 days every 3 weeks
-
Eribulin (IV) twice every 3 weeks
-
Gemcitabine (IV) twice every 3 weeks
-
Paclitaxel (IV) once every 3 weeks (Q3W) or once weekly (QW)
-
Vinolrebine (IV) twice every 3 weeks
干预措施: Gemcitabine (Drug)
Evorpacept+Trastuzumab+Chemo in participants with metastatic HER2+ breast cancer
-
Evorpacept (IV) - once every 3 weeks (Q3W)
-
Trastuzumab (IV) - once every 3 weeks (Q3W)
-
Chemotherapy (physician selects one of the following):
-
Capecitabine (Oral) twice a day for 14 days every 3 weeks
-
Eribulin (IV) twice every 3 weeks
-
Gemcitabine (IV) twice every 3 weeks
-
Paclitaxel (IV) once every 3 weeks (Q3W) or once weekly (QW)
-
Vinolrebine (IV) twice every 3 weeks
干预措施: Trastuzumab (Drug)
Evorpacept+Trastuzumab+Chemo in participants with metastatic HER2+ breast cancer
-
Evorpacept (IV) - once every 3 weeks (Q3W)
-
Trastuzumab (IV) - once every 3 weeks (Q3W)
-
Chemotherapy (physician selects one of the following):
-
Capecitabine (Oral) twice a day for 14 days every 3 weeks
-
Eribulin (IV) twice every 3 weeks
-
Gemcitabine (IV) twice every 3 weeks
-
Paclitaxel (IV) once every 3 weeks (Q3W) or once weekly (QW)
-
Vinolrebine (IV) twice every 3 weeks
干预措施: Paclitaxel (Drug)
Evorpacept+Trastuzumab+Chemo in participants with metastatic HER2+ breast cancer
-
Evorpacept (IV) - once every 3 weeks (Q3W)
-
Trastuzumab (IV) - once every 3 weeks (Q3W)
-
Chemotherapy (physician selects one of the following):
-
Capecitabine (Oral) twice a day for 14 days every 3 weeks
-
Eribulin (IV) twice every 3 weeks
-
Gemcitabine (IV) twice every 3 weeks
-
Paclitaxel (IV) once every 3 weeks (Q3W) or once weekly (QW)
-
Vinolrebine (IV) twice every 3 weeks
干预措施: Eribulin (Drug)
Evorpacept+Trastuzumab+Chemo in participants with metastatic HER2+ breast cancer
-
Evorpacept (IV) - once every 3 weeks (Q3W)
-
Trastuzumab (IV) - once every 3 weeks (Q3W)
-
Chemotherapy (physician selects one of the following):
-
Capecitabine (Oral) twice a day for 14 days every 3 weeks
-
Eribulin (IV) twice every 3 weeks
-
Gemcitabine (IV) twice every 3 weeks
-
Paclitaxel (IV) once every 3 weeks (Q3W) or once weekly (QW)
-
Vinolrebine (IV) twice every 3 weeks
干预措施: Capecitabine (Drug)
结局指标
主要结局
Overall Response Rate (ORR) using RECIST v1.1 based on BICR assessment
时间窗: Approximately 6 months after the last participant is enrolled
Evaluate the ORR of evorpacept in combination with trastuzumab and single-agent chemotherapy in the sub-population of participants with metastatic HER2-positive breast cancer who express CD47 (CD47+). ORR is defined as a best overall response (BOR) of confirmed complete response (CR) or partial response (PR) using RECIST v1.1 based on BICR assessment.
MBC substudy: Overall Response Rate (ORR) using RECIST v1.1 based on BICR assessment
时间窗: Approximately 6 months after the last participant is enrolled
Evaluate the ORR of evorpacept in combination with trastuzumab and single-agent chemotherapy in the sub-population of participants with metastatic HER2-positive ctDNA-positive breast cancer. ORR is defined as a best overall response (BOR) of confirmed complete response (CR) or partial response (PR) using RECIST v1.1 based on BICR assessment.
次要结局
- Clearance (CL)(Approximately 6 months after the last participant is enrolled)
- Overall Response Rate (ORR) based on Investigator assessment(Approximately 6 months after the last participant is enrolled)
- Clinical Benefit Rate (CBR) using RECIST v1.1 based on BICR and Investigator assessment(Approximately 6 months after the last participant is enrolled)
- Duration of Response (DoR) using RECIST v1.1 based on BICR and Investigator assessment(Approximately 6 months after the last participant is enrolled)
- Progression-Free Survival (PFS) using RECIST v1.1 based on BICR and Investigator assessment(Approximately 6 months after the last participant is enrolled)
- Overall Survival (OS)(Approximately 6 months after the last participant is enrolled)
- Number of participants with adverse events (AEs) and with laboratory abnormalities(Enrollment to 28 days after the last administration of the study drug)
- Maximum Concentration (Cmax)(Approximately 6 months after the last participant is enrolled)
- Time at Maximum Concentration (Tmax)(Approximately 6 months after the last participant is enrolled)
- Area under the Concentration-Time Curve (AUC)(Approximately 6 months after the last participant is enrolled)
- Terminal elimination half-life (t1/2)(Approximately 6 months after the last participant is enrolled)
- Evaluate the immunogenicity of evorpacept(Approximately 6 months after the last participant is enrolled)
- MBC substudy: Clinical Benefit Rate (CBR) using RECIST v1.1 based on BICR and Investigator assessment(Approximately 6 months after the last participant is enrolled)
- MBC substudy: Progression-Free Survival (PFS) using RECIST v1.1 based on BICR and Investigator assessment(Approximately 6 months after the last participant is enrolled)
- All substudies: Time at Maximum Concentration (Tmax)(Approximately 6 months after the last participant is enrolled)
- All substudies: Evaluate the immunogenicity of evorpacept(Approximately 6 months after the last participant is enrolled)
- MBC substudy: Overall Response Rate (ORR) based on Investigator assessment(Approximately 6 months after the last participant is enrolled)
- MBC substudy: Duration of Response (DoR) using RECIST v1.1 based on BICR and Investigator assessment(Approximately 6 months after the last participant is enrolled)
- All substudies: Area under the Concentration-Time Curve (AUC)(Approximately 6 months after the last participant is enrolled)
- All substudies: Maximum Concentration (Cmax)(Approximately 6 months after the last participant is enrolled)
- All substudies: Clearance (CL)(Approximately 6 months after the last participant is enrolled)
- All substudies: Terminal elimination half-life (t1/2)(Approximately 6 months after the last participant is enrolled)
- MBC substudy: Overall Survival (OS)(Approximately 6 months after the last participant is enrolled)
- MBC substudy: Number of participants with adverse events (AEs) and with laboratory abnormalities(Enrollment to 28 days after the last administration of the study drug)