HERTHENA-PanTumor01 (U31402-277): A Phase 2, Multicenter, Multicohort, Open-Label, Proof of Concept Study of Patritumab Deruxtecan (HER3-DXd; U3-1402) in Subjects With Locally Advanced or Metastatic Solid Tumors
概览
- 阶段
- 2 期
- 干预措施
- HER3-DXd
- 疾病 / 适应症
- 未指定
- 发起方
- Daiichi Sankyo
- 入组人数
- 740
- 试验地点
- 160
- 主要终点
- Number of Participants With Objective Response Rate Assessed by Investigator Following HER3-DXd Monotherapy (All Cohorts Except Prostate Cancer Cohort)
- 状态
- 招募中
- 最后更新
- 3个月前
概览
简要总结
This is a proof-of-concept study designed to investigate HER3-DXd monotherapy in locally advanced unresectable or metastatic solid tumors. The study is enrolling cohorts of participants with melanoma [cutaneous/acral], squamous cell carcinomas of the head and neck (SCCHN), HER2-negative gastric cancer ovarian carcinoma, cervical cancer, endometrial cancer, bladder cancer, esophageal carcinoma, pancreatic carcinoma, prostate cancer, second-line gastric cancer, lung cancer, and breast cancer.
详细描述
This study is designed to assess the safety and efficacy of HER3-DXd monotherapy in subjects with refractory locally advanced unresectable or metastatic solid tumors who have been previously treated with ≥1 prior line of systemic anticancer therapy. The primary objective of the study is to assess the efficacy of HER3-DXd monotherapy for each type of indicated locally advanced unresectable or metastatic tumor. Secondary objectives include the assessment of safety and tolerability, efficacy, and pharmacokinetics of HER3-DXd monotherapy for each type of indicated locally advanced unresectable or metastatic tumor. HER3 protein expression in tumor tissue and its relationship with HER3-DXd efficacy will also be evaluated.
研究者
入排标准
入选标准
- •Participants must meet all of the following criteria to be eligible for enrollment into the study:
- •Sign and date the informed consent form prior to the start of any study-specific qualification procedures. A separate tissue screening consent will be obtained from all subjects to meet the baseline tumor tissue requirement.
- •Participants aged ≥18 years (follow local regulatory requirements if the legal age of consent for study participation is \>18 years old).
- •Has locally advanced unresectable or metastatic disease (not curable by surgery or radiation) as follows:
- •Cutaneous (acral and non-acral) melanoma
- •Histologically or cytologically confirmed cutaneous (acral or non-acral) melanoma
- •Disease progression while on or after having received treatment with ≥1 prior line of anti-programmed cell death protein (PD-1) or anti-programmed death-ligand 1 (PD-L1) based therapy (previous use of other immune checkpoint inhibitors \[ICIs\] \[ie, anti-CTLA4, anti- LAG-3\] is acceptable). Prior anti-PD-(L)1 therapy in the adjuvant setting is allowed if there is recurrence within 12 weeks of the last dose. If the participant had BRAFm melanoma, they must have had disease progression on BRAF/MEK inhibitor therapy as well.
- •Squamous cell carcinomas of the head and neck
- •Squamous cell carcinoma of the head and neck (with a primary location of oral cavity,oropharynx, larynx, hypopharynx) that is human papillomavirus (HPV) positive or negative (as determined by local standard). Excludes tumor location in the nasopharynx, nasal cavity, paranasal sinuses, and unknown primary locations.
- •Disease progression after having received treatment with ≥1 and \<3 prior lines of systemic therapy in the unresectable recurrent or metastatic setting.
排除标准
- •Participants who meet any of the following criteria will be disqualified from entering the study:
- •Has HER2-positive gastric cancer as classified by ASCO-CAP guidelines and determined prior to enrollment by assessment in a local laboratory that is Clinical Laboratory Improvement Amendments certified (US sites) or accredited based on specific country regulations.
- •Has nasopharyngeal cancer.
- •Has mucosal or uveal melanoma.
- •Has a history of (non-infectious) interstitial lung disease (ILD), that required corticosteroids, has current ILD/pneumonitis, or suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
- •Has clinically severe respiratory compromise (based on the investigator's assessment) resulting from intercurrent pulmonary illnesses
- •Is receiving chronic systemic corticosteroids dosed at \>10 mg prednisone daily or equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior to Cycle 1 Day
- •Participants who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the study.
- •Had prior treatment with an anti-HER3 antibody and/or antibody-drug conjugate (ADC) that consists of an exatecan derivative that is a topoisomerase I inhibitor (eg, trastuzumab deruxtecan).
- •Has history of other active malignancy within 3 years prior to Cycle 1 Day 1, except the following:
研究组 & 干预措施
HER3-DXd Monotherapy
Participants with locally advanced unresectable or metastatic cancer (melanoma, head and neck, gastric cancer, ovarian carcinoma, cervical cancer, endometrial cancer, bladder cancer, esophageal carcinoma, pancreatic carcinoma, prostate cancer, second-line gastric cancer, lung cancer, and breast cancer) will receive an intravenous infusion of HER3-DXd monotherapy 5.6 mg/kg every 3 weeks (Q3W).
干预措施: HER3-DXd
结局指标
主要结局
Number of Participants With Objective Response Rate Assessed by Investigator Following HER3-DXd Monotherapy (All Cohorts Except Prostate Cancer Cohort)
时间窗: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 27 months
Confirmed objective response rate (ORR) is defined as the sum of the complete response (CR) rate and partial response (PR) rate based on investigator by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
Proportion of Participants Achieving a ≥50% Decrease in PSA (Prostate Cancer Cohort Only)
时间窗: Baseline, each cycle before infusion (each cycle is 21 days), and end of treatment, up to approximately 27 months
次要结局
- Overall Number of Participants With Treatment-emergent Adverse Events Following HER3-DXd Monotherapy (All Cohorts)(Baseline up to 27 months)
- Duration of Response As Assessed by Investigator Following HER3-DXd Monotherapy (All Cohorts Except Prostate Cancer Cohort)(From the date of first documentation of confirmed response (CR or PR) to the first documentation of objective progression or to death due to any cause, whichever occurs first, up to approximately 27 months)
- Clinical Benefit Rate As Assessed by Investigator Following HER3-DXd Monotherapy (All Cohorts Except Prostate Cancer Cohort)(Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 27 months)
- Disease Control Rate As Assessed by Investigator Following HER3-DXd Monotherapy (All Cohorts Except Prostate Cancer Cohort)(Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 27 months)
- Time to Response As Assessed by Investigator Following HER3-DXd Monotherapy (All Cohorts Except Prostate Cancer Cohort)(From the start date of study drug to the date of the first documentation of response (CR or PR) that is subsequently confirmed, up to approximately 27 months)
- Progression-free Survival As Assessed by Investigator Following HER3-DXd Monotherapy (All Cohorts Except Prostate Cancer Cohort)(From the start date of study drug to the earlier date of the first objective documentation of radiographic disease progression as assessed by investigator per RECIST v1.1 or death due to any cause, whichever occurs first, up to approximately 27 months)
- Overall Survival Following HER3-DXd Monotherapy (All Cohorts)(From the start date of study drug to the date of death due to any cause, whichever occurs first, up to approximately 27 months)
- Pharmacokinetic Parameter Maximum Serum Concentration for HER3-DXd (All Cohorts)(Cycles 1-4, 6, 8: Day 1, predose and postdose; Cycles 1 and 3: Day 1, 2 hours and 4 hours postdose; Cycles 1 and 3: Day 8, Day 15 (each cycle is 21 days))
- Pharmacokinetic Parameter Time to Maximum Serum Concentration for HER3-DXd (All Cohorts)(Cycles 1-4, 6, 8: Day 1, predose and postdose; Cycles 1 and 3: Day 1, 2 hours and 4 hours postdose; Cycles 1 and 3: Day 8, Day 15 (each cycle is 21 days))
- Pharmacokinetic Parameter Trough Serum Concentration (Ctrough) for HER3-DXd (All Cohorts)(Cycles 1-4, 6, 8: Day 1, predose and postdose; Cycles 1 and 3: Day 1, 2 hours and 4 hours postdose; Cycles 1 and 3: Day 8, Day 15 (each cycle is 21 days))
- Pharmacokinetic Parameter Area Under the Concentration Curve for HER3-DXd (All Cohorts)(Cycles 1-4, 6, 8: Day 1, predose and postdose; Cycles 1 and 3: Day 1, 2 hours and 4 hours postdose; Cycles 1 and 3: Day 8, Day 15 (each cycle is 21 days))
- Radiographic Progression-free Survival (rPFS) As Assessed by Prostate Cancer Working Group 3 (PCWG3) Criteria by the Investigator or Death Due to Any Cause Following HER3-DXd Monotherapy (Prostate Cancer Cohort Only)(From the start date of study drug to the earlier date of the first objective documentation of radiographic disease progression as assessed per PCWG3 criteria by investigator or death due to any cause, whichever occurs first, up to approximately 27 months)
- Proportion of Participants Achieving a ≥30% Decrease in PSA (Prostate Cancer Cohort Only)(Baseline, each cycle before infusion (each cycle is 21 days), and end of treatment, up to approximately 27 months)
- Time to First Subsequent Anticancer Therapy (TFST) (Prostate Cancer Cohort Only)(From the start date of study drug to initiation of the first subsequent anticancer therapy or death, whichever occurs first, up to approximately 27 months)
- Time to First Symptomatic Skeletal-Related Event (SSRE) (Prostate Cancer Cohort Only)(From start date of study drug to the first occurrence of any of the following: Use of EBRT, New symptomatic pathologic bone fracture, Spinal cord compression, A tumor-related orthopedic surgical intervention, up to approximately 27 months)
- Correlation Between HER3 Protein Expression and Efficacy(From the start date of study drug up to approximately 27 months)