A Phase 1 Open-Label Study to Evaluate the Efficacy and Safety of ABBV-400 in Select Advanced Solid Tumor Indications
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 325
- 试验地点
- 193
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. The purpose of this study is to assess adverse events and change in disease activity when ABBV-400 is given to adult participants to treat advanced solid tumors.
ABBV-400 is an investigational drug being developed for the treatment of advanced solid tumors. Study doctors put the participants in groups called cohorts. Cohorts 1-8 receive ABBV-400 alone (monotherapy), cohort 9 receives ABBV-400 with a strong CYP3A3 inhibitor (ITZ), and cohort 10 receives ABBV-400 with bevacizumab. All cohorts are followed by a safety follow-up period. Approximately 325 adult participants with hepatocellular carcinoma (HCC), pancreatic ductal adenocarcinoma (PDAC), biliary tract cancers (BTC), esophageal squamous cell carcinoma (ESCC), triple negative breast cancer (TNBC), hormone receptor+/human epidermal growth factor receptor 2 negative (HER2-) breast cancer (hormone receptor-positive [HR+]/HER2-breast cancer [BC]), head and neck squamous-cell-carcinoma (HNSCC), Platinum Resistant High Grade Epithelial Ovarian Cancer (PROC)/primary peritoneal/fallopian tube cancer, or advanced solid tumors, will be enrolled in the study in approximately 54 sites worldwide.
In cohorts 1-8, participants with the following advanced solid tumor indications: HCC, PDAC, BTC, ESCC, TNBC, HR+/HER2-BC, HNSCC, and PROC/primary peritoneal/fallopian tube cancer will receive intravenous (IV) ABBV-400 monotherapy, in cohort 9 participants will receive IV ABBV-400 and an oral solution of ITZ, and in cohort 10 participants will receive IV ABBV-400 and IV bevacizumab, for up to 3 years during and up to the treatment period with an additional safety follow-up period of up to 2 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 an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Laboratory values meeting the criteria laid out in the protocol.
- •Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.
- •Documented diagnosis of locally advanced or metastatic hepatocellular carcinoma (HCC), pancreatic ductal adenocarcinoma (PDAC), biliary tract cancers (BTC), squamous cell carcinoma of the esophagus, (ESCC), triple negative breast cancer (TNBC), hormone receptor+/HER2-breast cancer (HR+/HER2-BC), head and neck squamous-cell-carcinoma (HNSCC), or Platinum Resistant High Grade Epithelial Ovarian Cancer (PROC)/primary peritoneal/fallopian tube cancer (by World Health Organization [WHO] criteria). Participant meets the criteria for disease activity laid out in the protocol.
排除标准
- •Have received anticancer therapy including chemotherapy, radiation therapy, immunotherapy, biologic, or any investigational therapy within 28 days or 5 half-lives of the drug (whichever is shorter) prior to the first dose of ABBV-
- •Palliative radiation therapy for bone, skin, or subcutaneous metastases with 10 fractions or less is permitted and not subject to a washout period.
- •Unresolved clinically significant AEs > Grade 1 from prior anticancer therapy.
- •History of interstitial lung disease (ILD) or pneumonitis that required treatment with systemic steroids, or any evidence of active ILD or pneumonitis, including but not limited to those listed in the protocol.
- •History of clinically significant, intercurrent lung-specific illnesses, including those laid out in the protocol.
- •Untreated brain or meningeal metastases (i.e., participants with history of metastases are eligible provided they do not require ongoing steroid treatment for cerebral edema and have shown clinical and radiographic stability for at least 14 days after definitive therapy). Participants may continue on antiepileptic therapy if required.
- •History of other active malignancy, with the exception of those laid out in the protocol.
- •Any autoimmune, connective tissue or inflammatory disorders with documented or suspicious pulmonary involvement at screening (i.e., rheumatoid arthritis, Sjogren's, sarcoidosis etc.), and prior pneumonectomy.
研究组 & 干预措施
Cohort 10: PROC/Primary Peritoneal/Fallopian Tube Cancer
Participants with PROC/primary peritoneal/fallopian tube cancer will receive ABBV-400 in combination with bevacizumab for up to 3 years during and up to the treatment period with an additional safety follow-up period of up to 2 years.
干预措施: ABBV-400 (Drug)
Cohort 10: PROC/Primary Peritoneal/Fallopian Tube Cancer
Participants with PROC/primary peritoneal/fallopian tube cancer will receive ABBV-400 in combination with bevacizumab for up to 3 years during and up to the treatment period with an additional safety follow-up period of up to 2 years.
干预措施: Bevacizumab (Drug)
Cohort 5: Triple Negative Breast Cancer (TNBC)
Participants with TNBC will receive ABBV-400 for up to 3 years during and up to the treatment period with an additional safety follow-up period of up to 2 years.
干预措施: ABBV-400 (Drug)
Cohort 2: Pancreatic Ductal Adenocarcinoma (PDAC)
Participants with PDAC will receive ABBV-400 for up to 3 years during and up to the treatment period with an additional safety follow-up period of up to 2 years.
干预措施: ABBV-400 (Drug)
Cohort 4: Esophageal Squamous Cell Carcinoma, (ESCC)
Participants with ESCC will receive ABBV-400 for up to 3 years during and up to the treatment period with an additional safety follow-up period of up to 2 years.
干预措施: ABBV-400 (Drug)
Cohort 1: Hepatocellular Carcinoma (HCC)
Participants with HCC will receive ABBV-400 for up to 3 years during and up to the treatment period with an additional safety follow-up period of up to 2 years.
干预措施: ABBV-400 (Drug)
Cohort 3: Biliary Tract Cancers (BTC)
Participants with BTC will receive ABBV-400 for up to 3 years during and up to the treatment period with an additional safety follow-up period of up to 2 years.
干预措施: ABBV-400 (Drug)
Cohort 7: Head and Neck Squamous-cell-carcinoma (HNSCC)
Participants with HNSCC will receive ABBV-400 for up to 3 years during and up to the treatment period with an additional safety follow-up period of up to 2 years.
干预措施: ABBV-400 (Drug)
Cohort 8: PROC/Primary Peritoneal/Fallopian Tube Cancer
Participants with Platinum Resistant High Grade Epithelial Ovarian Cancer (PROC)/primary peritoneal/fallopian tube cancer will receive ABBV-400 for up to 3 years during and up to the treatment period with an additional safety follow-up period of up to 2 years.
干预措施: ABBV-400 (Drug)
Cohort 9: Drug-Drug Interaction
Participants with advanced or metastatic solid tumors will receive ABBV-400 and a strong CYP3A4 inhibitor (ITZ) for up to 3 years during and up to the treatment period with an additional safety follow-up period of up to 2 years.
干预措施: ABBV-400 (Drug)
Cohort 6: Hormone Receptor+/HER2-breast Cancer (HR+/HER2-BC)
Participants with HR+/HER2-BC will receive ABBV-400 for up to 3 years during and up to the treatment period with an additional safety follow-up period of up to 2 years.
干预措施: ABBV-400 (Drug)
Cohort 9: Drug-Drug Interaction
Participants with advanced or metastatic solid tumors will receive ABBV-400 and a strong CYP3A4 inhibitor (ITZ) for up to 3 years during and up to the treatment period with an additional safety follow-up period of up to 2 years.
干预措施: Itraconazole (ITZ) (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: Up to 36 Months
ORR defined as percentage of participants with confirmed best overall response of confirmed partial response (PR) or better per investigator review according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Number of Participants with Adverse Events (AEs)
时间窗: Up to 36 Months
An AE is defined as any untoward medical occurrence in a patient or clinical investigation in which a participant is administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment.
Maximum Observed Concentration (Cmax) of ABBV-400 Conjugate
时间窗: Up to 36 Months
Cmax of ABBV-400 conjugate.
AUC from Time 0 to the End of Dosing Interval (AUCtau) of ABBV-400 Conjugate
时间窗: Up to 36 Months
AUCtau of ABBV-400 conjugate.
次要结局
- CLss of ABBV-400 Unconjugated(Up to 36 Months)
- Duration of Response (DOR) for Participants with Confirmed Complete Response (CR)/PR(Up to 36 Months)
- Clinical Benefit Rate(Up to 36 Months)
- Progression-free Survival (PFS)(Up to 36 Months)
- Overall Survival (OS)(Up to 36 Months)
- Cmax of ABBV-400(Up to 36 Months)
- Time to Cmax (Tmax) of ABBV-400(Up to 36 Months)
- Area Under the Plasma Concentration-time Curve (AUC) for Total Antibody Concentration(Up to 36 Months)
- Total Antibody Drug Conjugate (ADC) Concentration(Up to 36 Months)
- Plasma Concentrations of Unconjugated Topoisomerase 1 (Top1) Inhibitor Payload(Up to 36 Months)
- Antidrug Antibody (ADA)(Up to 36 Months)
- Neutralizing Antidrug Antibody (nADA)(Up to 36 Months)
- Tmax of ABBV-400 Conjugate(Up to 36 Months)
- Tmax of ABBV-400 Unconjugated(Up to 36 Months)
- Terminal Phase Elimination Half-Life (t1/2) of ABBV-400 Conjugate(Up to 36 Months)
- t1/2 of ABBV-400 Unonjugated(Up to 36 Months)
- Volume of Distribution at Steady State (Vss) of ABBV-400 Conjugate(Up to 36 Months)
- Vss of ABBV-400 Unconjugated(Up to 36 Months)
- Total Body Clearance at Steady State (CLss) of ABBV-400 Conjugate(Up to 36 Months)
- CLss of ABBV-400 Unconjugated(Up to 36 Months)