A Phase 1 First-in-Human, Open-Label Study Evaluating Safety, Pharmacokinetics, and Efficacy of ABBV-901 as a Monotherapy and in Combination in Adult Subjects With Ovarian Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 285
- 试验地点
- 32
- 主要终点
- Overall Response (as assessed by the investigator)
研究概览
简要总结
Ovarian cancer (OC) is a lethal disease. The purpose of this study is to assess the safety, pharmacokinetics and efficacy of ABBV901, alone or in combination with other anticancer drugs, in participants with ovarian cancer.
ABBV901 is an investigational drug for the treatment of ovarian cancer. This study has 6 parts where participants will receive ABBV-901, alone or in combination with other anticancer therapies. Around 285 participants will be enrolled in the study at approximately 45 sites around the world.
In part 1, participants will receive escalating doses of intravenous (IV) ABBV-901 alone. In part 2, participants will receive 1 of 3 doses of IV ABBV-901 alone to determine the optimized dose. In part 3, participants will receive escalating doses of IV ABBV-901 in combination with IV bevacizumab. In part 4, participants will receive recommended doses for expansion of IV ABBV-901 combination with IV bevacizumab. in Part 5, participants will receive escalating doses of IV ABBV-901 in combination with IV carboplatin and IV bevacizumab and in part 6, participants will receive recommended doses for expansion of IV ABBV-901 combination with IV carboplatin and IV bevacizumab. The total study duration will be approximately 3 years.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic and may require frequent medical assessments, blood tests, and scans.
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
- •Diagnosis of an advanced or unresectable malignant high grade serous epithelial ovarian, fallopian tube, and primary peritoneal cancers (EOC), fallopian tube or primary peritoneal cancer by histology (World Health Organization [WHO] criteria).
- •Participants enrolled in backfill (Part 1) must provide consent to paired fresh biopsies which are pretreatment and on-treatment tumor biopsies from the same tumor lesion.
- •For Parts 1-4:
- •- Participants must be considered platinum resistant or platinum ineligible. Platinum resistant disease is defined as radiographic progression within 6 months (up to 182 days) after the last dose of the most recent platinum therapy).
- •For Parts 5-6:
- •- Participants will have platinum-sensitive disease defined as radiographic progression > 6 months from last dose of platinum-based chemotherapy. Note: Progression should be calculated from the date of the last administered dose of platinum therapy to the date of the radiographic imaging showing progression.
排除标准
- •Ovarian Cancer (OC) with histologies other than high grade serous OC including endometrioid, low grade, mucinous, carcinosarcoma or sarcomatous histology, mixed tumors or low grade/borderline ovarian tumor.
- •Participants with platinum refractory disease.
- •Prior therapy with an antibody-drug conjugate containing a topoisomerase inhibitor.
- •Prior history of Grade >= 2 interstitial lung disease (ILD) or pneumonitis.
- •Prior history of Grade 2 >= 2 ILD or pneumonitis or any evidence of active ILD or pneumonitis on Screening chest computed tomography (CT) scan.
- •For Parts 3-6:
- •History of Grade 3/4 adverse events that, in the opinion of the investigator, are attributed to bevacizumab.
- •History of clinically significant cardiac disease including CHF Class II or higher NYHA; active coronary artery disease, MI within 6 months prior to study entry; unevaluated new onset angina within 3 months or unstable angina (angina symptoms at rest) or cardiac arrhythmias requiring antiarrhythmic therapy (beta blockers or digoxin are permitted).
- •Echocardiogram with ejection fraction <= 50% and no other clinically significant cardiac abnormalities that in the opinion of the investigator, would increase the participants susceptibility to cardiac toxicity.
- •For Parts 5-6:
- •- Participants who had prior allergic reaction to platinum containing compound.
研究组 & 干预措施
Part 4: ABBV-901 + Bevacizumab Expansion
Participants will receive the recommended doses for expansion doses of ABBV-901 in combination Bevacizumab, as part of the approximately 3 year study duration.
干预措施: Bevacizumab (Drug)
Part 1: ABBV-901 Dose Escalation
Participants will receive escalating doses of ABBV-901 alone, as part of the approximately 3 year study duration.
干预措施: ABBV-901 (Drug)
Part 4: ABBV-901 + Bevacizumab Expansion
Participants will receive the recommended doses for expansion doses of ABBV-901 in combination Bevacizumab, as part of the approximately 3 year study duration.
干预措施: ABBV-901 (Drug)
Part 2: ABBV-901 Optimization Dose A
Participants will receive ABBV-901 dose A alone, as part of the approximately 3 year study duration.
干预措施: ABBV-901 (Drug)
Part 2: ABBV-901 Optimization Dose B
Participants will receive ABBV-901 dose B alone, as part of the approximately 3 year study duration.
干预措施: ABBV-901 (Drug)
Part 2: ABBV-901 Optimization Dose C
Participants will receive ABBV-901 dose C alone, as part of the approximately 3 year study duration.
干预措施: ABBV-901 (Drug)
Part 5: ABBV-901 + Carboplatin + Bevacizumab Escalation
Participants will receive escalating doses of ABBV-901 in combination with Carboplatin & Bevacizumab, as part of the approximately 3 year study duration.
干预措施: ABBV-901 (Drug)
Part 6: ABBV-901 + Carboplatin + Bevacizumab Expansion
Participants will receive the recommended doses for expansion doses of ABBV-901 in combination with Carboplatin & Bevacizumab, as part of the approximately 3 year study duration.
干预措施: ABBV-901 (Drug)
Part 6: ABBV-901 + Carboplatin + Bevacizumab Expansion
Participants will receive the recommended doses for expansion doses of ABBV-901 in combination with Carboplatin & Bevacizumab, as part of the approximately 3 year study duration.
干预措施: Bevacizumab (Drug)
Part 6: ABBV-901 + Carboplatin + Bevacizumab Expansion
Participants will receive the recommended doses for expansion doses of ABBV-901 in combination with Carboplatin & Bevacizumab, as part of the approximately 3 year study duration.
干预措施: Carboplatin (Drug)
Part 5: ABBV-901 + Carboplatin + Bevacizumab Escalation
Participants will receive escalating doses of ABBV-901 in combination with Carboplatin & Bevacizumab, as part of the approximately 3 year study duration.
干预措施: Bevacizumab (Drug)
Part 5: ABBV-901 + Carboplatin + Bevacizumab Escalation
Participants will receive escalating doses of ABBV-901 in combination with Carboplatin & Bevacizumab, as part of the approximately 3 year study duration.
干预措施: Carboplatin (Drug)
Part 3: ABBV-901 + Bevacizumab Escalation
Participants will receive escalating doses of ABBV-901 in combination Bevacizumab, as part of the approximately 3 year study duration.
干预措施: ABBV-901 (Drug)
Part 3: ABBV-901 + Bevacizumab Escalation
Participants will receive escalating doses of ABBV-901 in combination Bevacizumab, as part of the approximately 3 year study duration.
干预措施: Bevacizumab (Drug)
结局指标
主要结局
Overall Response (as assessed by the investigator)
时间窗: Up to Approximately 3 Years
Overall response is defined as participants achieving confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as assessed by the investigator.
Number of Participants with Adverse Events (AE)
时间窗: Up to Approximately 3 Years
An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have a causal relationship with this treatment.
Overall Response
时间窗: Up to Approximately 3 Years
Overall response is defined as participants achieving confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as assessed by the investigator.
次要结局
- Overall Response (as assessed by independent central review)(Up to Approximately 3 Years)
- Duration of Response (DOR)(Up to Approximately 3 Years)
- Progression-free survival (PFS)(Up to Approximately 3 Years)
- Overall Survival (OS)(Up to Approximately 3 Years)
- Disease Control Rate(Up to Approximately 3 Years)