A Phase 1 Study to Evaluate the Safety and Tolerability of AB680 Combination Therapy in Participants With Gastrointestinal Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 196
- 试验地点
- 29
- 主要终点
- Number of participants with Treatment Emergent Adverse Events (TEAEs)
研究概览
简要总结
This is a Phase 1, open-label, dose-escalation, and dose-expansion, with a gated randomization portion, study to evaluate the safety, tolerability, pharmacokinetic, pharmacodynamic and clinical activity of AB680 in combination with zimberelimab (AB122), nab-paclitaxel and gemcitabine in participants with advanced pancreatic cancer.
详细描述
Dose escalation of AB680 in combination with zimberelimab (AB122), nab-paclitaxel and gemcitabine will be assessed in participants with advanced pancreatic cancer. In this dose escalation combination study, participants with advanced pancreatic cancer will receive escalating doses of AB680 in combination with zimberelimab at the recommended phase 2 dose (RP2D), and nab-paclitaxel and gemcitabine at standard doses. AB680, zimberelimab, nab-paclitaxel and gemcitabine are all administered via IV infusion.
In the dose expansion portion of the study in front-line (1L) pancreatic patients, participants will receive AB680 at the RP2D determined from the dose escalation study in combination with zimberelimab at the RP2D and nab-paclitaxel and gemcitabine at standard doses or AB680 at the RP2D in combination with nab-paclitaxel and gemcitabine at standard doses. In the dose-expansion portion of the study in second-line (2L) pancreatic patients, participants will receive AB680 at the RP2D determined from the dose-escalation study in combination with zimberelimab at the RP2D and nab-paclitaxel and gemcitabine at standard doses.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 metastatic pancreatic adenocarcinoma
- •Naïve to any prior treatment, including chemotherapy, biological therapy, or targeted therapy for metastatic disease
- •Prior adjuvant therapy (including chemotherapy and/or radiotherapy) for pancreatic adenocarcinoma is permitted if neoadjuvant or adjuvant therapy was completed at least 6 months prior to study enrollment. Prior adjuvant therapy may include nab- paclitaxel or gemcitabine
- •Participants initially diagnosed with locally advanced pancreatic cancer who have undergone chemotherapy then resection and had no evidence of disease are eligible if relapse of metastatic disease has occurred and if the last dose of chemotherapy was received more than 6 months before study entry
- •Must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.
- •The measurable lesion must be outside of a radiation field if the participant received prior radiation
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
- •Confirmation that an archival tissue sample is available; if not, a new biopsy of a tumor must be obtained
- •Prior radiation therapy for metastatic disease must have been completed
- •Immunosuppressive doses of systemic medications, such as corticosteroids or absorbed topical corticosteroids (doses > 10 mg/day prednisone or equivalent) must be discontinued at least 2 weeks (14 days) before investigational product administration. Physiologic doses of corticosteroids (≤ 10 mg/day of prednisone or its equivalent) or short pulses of corticosteroids (≤ 3 days) may be permitted
- •Prior surgery that required general anesthesia or other major surgery as defined by the Investigator must be completed at least 4 weeks before investigational product administration
- •Negative tests for hepatitis B surface antigen, hepatitis C virus antibody (or hepatitis C qualitative ribonucleic acid [RNA; qualitative]), and human immunodeficiency virus (HIV)-1 and HIV-2 antibody at screening
- •Adequate organ and marrow function
排除标准
- •Significant cardiovascular disease (NYHA Class III-IV), myocardial infarction or cerebrovascular accident within 12 months of the first dose of investigational agent or history of arterial thromboembolic event, uncontrolled hypertension, unstable arrhythmia, or unstable angina within 3 months or venous thromboses within 1 month of the first dose of investigational agent.
- •Any active autoimmune disease or a documented history of autoimmune disease or history of a syndrome that required systemic steroids or immunosuppressive medications, except for vitiligo or resolved childhood asthma/atopy. Participants with asthma who require intermittent use of bronchodilators (such as albuterol) will not be excluded from this study
- •History of a syndrome that required systemic steroids or immunosuppressive medications, except for vitiligo or resolved childhood asthma/atopy. Participants with asthma who require intermittent use of bronchodilators (such as albuterol) will not be excluded from this study
- •Prior malignancy active within the previous year except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix, breast, or prostate cancer
- •Has not recovered (ie, ≤ Grade 1 or baseline) from a non-hematologic AEs due to a previously administered agent, except ≤ Grade 2 alopecia or ≤ Grade 2 neuropathy.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Dose Expansion (AB680+zimberelimab+NP/Gem):Cohort A1 (front-line/1L)
Participants with advanced pancreatic cancer, naïve to any prior treatment will receive AB680 (at the RP2D identified during dose escalation) combined with zimberelimab and the standard nab-paclitaxel (NP) and gemcitabine (Gem) (NP/Gem) chemotherapy regimen
干预措施: AB680 (Drug)
Dose Expansion (AB680+zimberelimab+ NP/Gem): Cohort A (front-line/1L)
Participants with advanced pancreatic cancer, naïve to any prior treatment will receive AB680 (at the RP2D identified during dose escalation) combined with zimberelimab and the standard nab-paclitaxel (NP) and gemcitabine (Gem) (NP/Gem) chemotherapy regimen
干预措施: Gemcitabine (Drug)
Dose Expansion (AB680+zimberelimab+ NP/Gem): Cohort A (front-line/1L)
Participants with advanced pancreatic cancer, naïve to any prior treatment will receive AB680 (at the RP2D identified during dose escalation) combined with zimberelimab and the standard nab-paclitaxel (NP) and gemcitabine (Gem) (NP/Gem) chemotherapy regimen
干预措施: Zimberelimab (Drug)
Dose Expansion (AB680 + NP/Gem): Cohort A2 (front-line/1L)
Participants with advanced pancreatic cancer who are naïve to any prior treatment will receive AB680 (at the RP2D identified during dose escalation) and the standard NP/Gem chemotherapy regimen.
干预措施: Gemcitabine (Drug)
Dose Expansion (AB680+zimberelimab+NP/Gem):Cohort A1 (front-line/1L)
Participants with advanced pancreatic cancer, naïve to any prior treatment will receive AB680 (at the RP2D identified during dose escalation) combined with zimberelimab and the standard nab-paclitaxel (NP) and gemcitabine (Gem) (NP/Gem) chemotherapy regimen
干预措施: Zimberelimab (Drug)
Dose Expansion (AB680 + NP/Gem): Cohort A2 (front-line/1L)
Participants with advanced pancreatic cancer who are naïve to any prior treatment will receive AB680 (at the RP2D identified during dose escalation) and the standard NP/Gem chemotherapy regimen.
干预措施: Nab-paclitaxel (Drug)
Dose Escalation
Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period. The dose expansion dose level will be determined in this part with escalating doses of AB680 in combination with zimberelimab at the recommended phase 2 dose (RP2D) and the standard nab-paclitaxel and gemcitabine chemotherapy regimen in participants with advanced pancreatic cancer.
干预措施: AB680 (Drug)
Dose Expansion (AB680+zimberelimab+NP/Gem):Cohort A1 (front-line/1L)
Participants with advanced pancreatic cancer, naïve to any prior treatment will receive AB680 (at the RP2D identified during dose escalation) combined with zimberelimab and the standard nab-paclitaxel (NP) and gemcitabine (Gem) (NP/Gem) chemotherapy regimen
干预措施: Gemcitabine (Drug)
Dose Expansion (AB680 + zimberelimab + NP/Gem): Cohort B (second-line/2L)
Participants with advance pancreatic cancer who have received 1 prior line of treatment will receive AB680 (at the RP2D identified during dose escalation) combined with zimberelimab and NP-Gem chemotherapy regimen.
干预措施: Gemcitabine (Drug)
Dose Expansion (AB680 + zimberelimab + NP/Gem): Cohort C (front-line/1L)
Participants with advanced pancreatic cancer naïve to any prior treatment will receive AB680 combined with zimberelimab and NP-Gem chemotherapy regimen.
干预措施: Gemcitabine (Drug)
Dose Expansion (AB680 + NP/Gem): Cohort D (front-line/1L)
Participants with advanced pancreatic cancer naïve to any prior treatment will receive AB680 combined with NP-Gem chemotherapy regimen.
干预措施: Nab-paclitaxel (Drug)
Dose Expansion (AB680 + NP/Gem): Cohort D (front-line/1L)
Participants with advanced pancreatic cancer naïve to any prior treatment will receive AB680 combined with NP-Gem chemotherapy regimen.
干预措施: AB680 (Drug)
Dose Expansion (AB680 + zimberelimab + NP/Gem): Cohort C (front-line/1L)
Participants with advanced pancreatic cancer naïve to any prior treatment will receive AB680 combined with zimberelimab and NP-Gem chemotherapy regimen.
干预措施: Zimberelimab (Drug)
Dose Expansion (AB680 + zimberelimab + NP/Gem): Cohort B (second-line/2L)
Participants with advance pancreatic cancer who have received 1 prior line of treatment will receive AB680 (at the RP2D identified during dose escalation) combined with zimberelimab and NP-Gem chemotherapy regimen.
干预措施: Zimberelimab (Drug)
Dose Expansion (AB680 + zimberelimab + NP/Gem): Cohort B (second-line/2L)
Participants with advance pancreatic cancer who have received 1 prior line of treatment will receive AB680 (at the RP2D identified during dose escalation) combined with zimberelimab and NP-Gem chemotherapy regimen.
干预措施: AB680 (Drug)
Dose Expansion (AB680 + zimberelimab + NP/Gem): Cohort C (front-line/1L)
Participants with advanced pancreatic cancer naïve to any prior treatment will receive AB680 combined with zimberelimab and NP-Gem chemotherapy regimen.
干预措施: Nab-paclitaxel (Drug)
Dose Expansion (AB680 + NP/Gem): Cohort D (front-line/1L)
Participants with advanced pancreatic cancer naïve to any prior treatment will receive AB680 combined with NP-Gem chemotherapy regimen.
干预措施: Gemcitabine (Drug)
Dose Escalation
Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period. The dose expansion dose level will be determined in this part with escalating doses of AB680 in combination with zimberelimab at the recommended phase 2 dose (RP2D) and the standard nab-paclitaxel and gemcitabine chemotherapy regimen in participants with advanced pancreatic cancer.
干预措施: Gemcitabine (Drug)
Dose Expansion (AB680 + NP/Gem): Cohort A2 (front-line/1L)
Participants with advanced pancreatic cancer who are naïve to any prior treatment will receive AB680 (at the RP2D identified during dose escalation) and the standard NP/Gem chemotherapy regimen.
干预措施: AB680 (Drug)
Dose Expansion (AB680+zimberelimab+ NP/Gem): Cohort A (front-line/1L)
Participants with advanced pancreatic cancer, naïve to any prior treatment will receive AB680 (at the RP2D identified during dose escalation) combined with zimberelimab and the standard nab-paclitaxel (NP) and gemcitabine (Gem) (NP/Gem) chemotherapy regimen
干预措施: AB680 (Drug)
Dose Expansion (AB680+zimberelimab+NP/Gem):Cohort A1 (front-line/1L)
Participants with advanced pancreatic cancer, naïve to any prior treatment will receive AB680 (at the RP2D identified during dose escalation) combined with zimberelimab and the standard nab-paclitaxel (NP) and gemcitabine (Gem) (NP/Gem) chemotherapy regimen
干预措施: Nab-paclitaxel (Drug)
Dose Expansion (AB680 + zimberelimab + NP/Gem): Cohort C (front-line/1L)
Participants with advanced pancreatic cancer naïve to any prior treatment will receive AB680 combined with zimberelimab and NP-Gem chemotherapy regimen.
干预措施: AB680 (Drug)
Dose Escalation
Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period. The dose expansion dose level will be determined in this part with escalating doses of AB680 in combination with zimberelimab at the recommended phase 2 dose (RP2D) and the standard nab-paclitaxel and gemcitabine chemotherapy regimen in participants with advanced pancreatic cancer.
干预措施: Zimberelimab (Drug)
Dose Expansion (AB680+zimberelimab+ NP/Gem): Cohort A (front-line/1L)
Participants with advanced pancreatic cancer, naïve to any prior treatment will receive AB680 (at the RP2D identified during dose escalation) combined with zimberelimab and the standard nab-paclitaxel (NP) and gemcitabine (Gem) (NP/Gem) chemotherapy regimen
干预措施: Nab-paclitaxel (Drug)
Dose Escalation
Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period. The dose expansion dose level will be determined in this part with escalating doses of AB680 in combination with zimberelimab at the recommended phase 2 dose (RP2D) and the standard nab-paclitaxel and gemcitabine chemotherapy regimen in participants with advanced pancreatic cancer.
干预措施: Nab-paclitaxel (Drug)
Dose Expansion (AB680 + zimberelimab + NP/Gem): Cohort B (second-line/2L)
Participants with advance pancreatic cancer who have received 1 prior line of treatment will receive AB680 (at the RP2D identified during dose escalation) combined with zimberelimab and NP-Gem chemotherapy regimen.
干预措施: Nab-paclitaxel (Drug)
结局指标
主要结局
Number of participants with Treatment Emergent Adverse Events (TEAEs)
时间窗: From first dose date to 90 days after the last dose (approximately 1 year)
Safety will be assessed by monitoring adverse events and clinically relevant changes in 12 lead Electrocardiogram (ECG) and Physical examination findings
Number of Participants With Dose Limiting Toxicities
时间窗: From First dose to day 28
次要结局
- Duration of response(Start date of response to first progression/death, up to 1 year)
- Disease control rate(First dose date to first progression/death)
- Overall survival(First dose date to date of death, up to 1 year)
- Progression free survival(First dose date to first progression/death)
- AB680 peak plasma concentration (Cmax)(Day 1 (sequential), day 2, day 3, day 8, day 15, day 29, day 36, day 43, day 57, day 85, day 197, day 309, day 421, 30 days after last dose, and 90 days after last dose)
- Zimberelimab peak plasma concentration (Cmax)(Day 1 (sequential), day 2, day 3, day 8, day 15, day 29, day 43, day 57, day 85, day 197, day 309, day 421, 30 days after last dose, and 90 days after last dose)
- AB680 time of peak concentration (Tmax)(Day 1 (sequential), day 2, day 3, day 8, day 15, day 29, day 36, day 43, day 57, day 85, day 197, day 309, day 421, 30 days after last dose, and 90 days after last dose)
- Zimberelimab time of peak concentration (Tmax)(Day 1 (sequential), day 2, day 3, day 8, day 15, day 29, day 43, day 57, day 85, day 197, day 309, day 421, 30 days after last dose, and 90 days after last dose)
- AB680 area under the plasma concentration versus time curve (AUC)(Day 1 (sequential), day 2, day 3, day 8, day 15, day 29, day 36, day 43, day 57, day 85, day 197, day 309, day 421, 30 days after last dose, and 90 days after last dose)
- Zimberelimab area under the plasma concentration versus time curve (AUC)(Day 1 (sequential), day 2, day 3, day 8, day 15, day 29, day 43, day 57, day 85, day 197, day 309, day 421, 30 days after last dose, and 90 days after last dose)
- Immunogenicity indicators: anti-drug antibodies (ADA)(Day 1, day 15, day 29, day 57, day 85, day 197, day 309, and day 421)
- Overall response rate(First dose date to progression or last tumor assessment, up to 1 year)