A Phase 1B/2 Pan-Tumor, Open-Label Study to Evaluate the Efficacy and Safety of Ifinatamab Deruxtecan (I-DXd) in Subjects With Recurrent or Metastatic Solid Tumors (IDeate-PanTumor02)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 680
- 试验地点
- 226
- 主要终点
- Number of Participants Reporting Treatment-emergent Adverse Events and Death in the HCC Cohort
研究概览
简要总结
This study is designed to assess the efficacy and safety of ifinatamab deruxtecan (I-DXD) in the following tumor types: endometrial cancer (EC); head and neck squamous cell carcinoma (HNSCC); pancreatic ductal adenocarcinoma (PDAC); colorectal cancer (CRC); hepatocellular carcinoma (HCC); adenocarcinoma of esophagus, gastroesophageal junction, and stomach (Ad-Eso/GEJ/gastric); urothelial carcinoma (UC); ovarian cancer (OVC); cervical cancer (CC); biliary tract cancer (BTC); human epidermal growth factor 2 (HER2)-low breast cancer (BC); HER2 immunohistochemistry (IHC) 0 BC; cutaneous melanoma; and neuroendocrine carcinoma (NEC).
详细描述
This study will evaluate the efficacy and safety of I-DXd in participants with recurrent or metastatic solid tumors. The study will be divided into 3 parts: Stage 1, Stage 2 and an optional Stage 3. Each cohort starts with Stage 1 and may continue to Stage 2 if sufficient safety and efficacy data are observed. The EC cohort may proceed to an optional Stage 3 expansion based on the totality of available data.
The HCC Safety Run-In (Phase 1) will assess the safety and tolerability of I-DXd in participants with HCC.
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
- •Participants must meet all of the following criteria to be included in the study:
- •Common Inclusion Criteria for All Participants
- •Participants must consent to provide a pretreatment tumor sample which has not been previously irradiated. Fresh biopsies are strongly preferred, however, if a fresh pretreatment biopsy is not feasible or the procedure is unsuccessful, an appropriate archival sample must be provided. The most recent archival sample obtained up to 5 years prior to consent is acceptable.
- •Participants ages ≥18 years (follow local regulatory requirements if the legal age of consent for study participation is >18 years).
- •At least 1 measurable lesion on computed tomography (CT) or magnetic resonance imaging (MRI) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), as assessed by the investigator.
- •Documentation of radiological disease progression on or after the previous standard-of-care regimen. For NEC participants for which the standard therapy does not exist OR for which the standard therapy is not appropriate by the investigator: presence of advanced/metastatic disease without previous regimen is acceptable.
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Additional Inclusion Criteria for EC Participants
- •Pathologically or cytologically documented EC of any histological carcinoma subtype or endometrial carcinosarcoma, irrespective of microsatellite instability or mismatch repair status.
- •Relapse or progression after a platinum-containing systemic treatment and an immune checkpoint inhibitor (ICI)-containing regimen (combined or sequential). Participants with actionable target tumor mutation should have been previously treated with targeted therapy, with a maximum of 3 prior lines of therapy for endometrial carcinoma or carcinosarcoma. Neoadjuvant/adjuvant therapy may count as 1 line of therapy if the subject progressed within 6 months after completion of therapy.
- •Additional Inclusion Criteria for HNSCC Participants
- •Pathologically or cytologically documented unresectable or metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx, excluding nasopharynx, nasal cavity and paranasal sinuses, and unknown primary.
- •Has disease progression after platinum-based and ICI treatment, whether administered in combination or separately. Participants with actionable target tumor mutation should have been previously treated with targeted therapy, with a maximum of 2 prior therapy lines for unresectable or metastatic HNSCC.
- •Participants without radiographic evidence of major blood vessel invasion/infiltration or tumor demonstrating a greater than (>)90-degree abutment or encasement of a major blood vessel.
- •Participants with no prior history of Grade greater than or equal to (≥)3 bleeding as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 within 28 days prior to the start of study drug related to the current head and neck cancer may be included in the study.
- •Documented p16 status for oropharyngeal cancer (historical results are acceptable if available).
- •Additional Inclusion Criterion for PDAC Participants
- •1. Pathologically or cytologically documented unresectable or metastatic pancreatic adenocarcinoma that has relapsed or progressed after 1 prior line of gemcitabine-based systemic therapy in the locally advanced/metastatic setting or after 2 lines of therapy if the participant has actionable target tumor mutation and has been previously treated with targeted therapy.
- •a. No prior treatment with topoisomerase I inhibitors, such as irinotecan or topotecan.
- •Additional Inclusion Criteria for CRC Participants
- •Pathologically or cytologically documented unresectable or metastatic CRC with microsatellite stable status (MSS).
- •Relapse or progression after 1 prior line of systemic therapy including a fluoropyrimidine plus oxaliplatin with or without anti-vascular endothelial growth factor (VEGF) monoclonal antibody (mAb) or anti-epidermal growth factor receptor mAb therapy, as clinically indicated, or relapse or progression after 2 lines of therapy if the subject has received targeted therapy.
- •Note: Prior adjuvant/neoadjuvant systemic cytotoxic chemotherapy will count as 1 line of prior systemic therapy if there is documented disease progression during therapy or within 6 months of chemotherapy completion.
- •No prior treatment with topoisomerase I inhibitors, such as irinotecan or topotecan.
- •Additional Inclusion Criteria for HCC Participants
- •Pathologically or cytologically documented unresectable or metastatic HCC (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible) or noninvasive diagnosis of HCC as per the American Association for the Study of Liver Diseases (AASLD) criteria in participants with a confirmed diagnosis of cirrhosis.
- •Relapse or progression after 1 prior line of an ICI-containing regimen (combination or monotherapy) in the locally advanced/metastatic setting, or relapse or progression after 2 lines of therapy if the participant has an actionable target tumor mutation and has been treated with targeted therapy.
- •Barcelona Clinic Liver Cancer (BCLC) Stage B or C.
- •Liver function status should be Child-Pugh (CP) Class A.
- •Albumin-Bilirubin (ALBI) Grade 1 within 7 days prior to the first dose of study drug.
- •Participants with large esophageal varices at risk of bleeding must be treated with conventional medical intervention: beta blockers or endoscopic treatment.
- •Additional Inclusion Criteria for Ad-eso/GEJ/Gastric Participants
- •Pathologically or cytologically documented unresectable or metastatic Ad-eso/GEJ/Gastric that has relapsed or progressed after 1 prior line of systemic therapy in the locally advanced/metastatic setting.
- •a. Participants with PD-(L)1+ or MSI-H/dMMR should receive ICI treatment if ICIs are standard of care in the country, unless the participant is ineligible for ICI treatment.
- •If the participant has known history of HER2 positivity (defined by IHC 3+ or IHC 2+ and in situ hybridization [ISH] positive, as classified by American Society of Clinical Oncology - College of American Pathologists [ASCO CAP]) or actionable target, the participant must have been previously treated with a targeted therapy.
- •Additional Inclusion Criteria for UC Participants
- •Pathologically or cytologically documented unresectable or metastatic UC of the bladder, renal pelvis, ureter, or urethra. Participants with histological variants are allowed if urothelial histology is predominant. Small cell/neuroendocrine tumors are not allowed even if mixed histology.
- •Relapse or progression after at least 1 prior line of ICI-containing systemic therapy, and 1 prior line of systemic chemotherapy, given in combination with other anticancer therapy or separately, with a maximum of 3 prior therapy lines.
- •At least 1 line of therapy should include enfortumab vedotin in countries where enfortumab vedotin is approved and available.
- •Perioperative systemic therapies will be counted as 1 line of therapy.
- •To meet inclusion criteria requirement of prior ICI-containing therapy, use in the perioperative or metastatic setting will suffice.
- •Participants with actionable target tumor mutation should have been previously treated with targeted therapy.
- •The same regimen administered twice in different disease settings will be counted as 1 line of prior therapy.
- •Additional Inclusion Criteria for CC Participants
- •Histologically confirmed unresectable or metastatic CC that was previously treated with ≥1 prior line of systemic therapy in the locally advanced or metastatic setting. Participants with actionable target tumor mutation should have been previously treated with targeted therapy.
- •Participants should receive prior anti-programmed death 1 (PD-1)//programmed death-ligand 1 (PD-L1) treatment and/or tisotumab vedotin if those are standard of care in the country, unless the participant is ineligible for these treatments.
- •Additional Inclusion Criteria for OVC Participants
- •Histologically confirmed high-grade serous OVC, high-grade endometrioid OVC, primary peritoneal cancer, or fallopian tube cancer that was previously treated with at least 1 line of platinum-based therapy and bevacizumab unless the participant is ineligible for treatment with bevacizumab.
- •Participant is no longer considered eligible for platinum-based therapy per the investigator's opinion or has progressed less than 180 days after the last dose of platinum therapy.
- •Participant is not considered primary platinum refractory and has not progressed during platinum treatment or within 4 weeks after the completion of platinum treatment.
- 另有 24 项未显示
排除标准
- •Participants who meet any of the following criteria will be disqualified from entering the study:
- •Prior treatment with orlotamab, enoblituzumab, or other B7-homologue 3 (B7-H3)-targeted agents, including I-DXd.
- •Prior discontinuation of an antibody drug conjugate (ADC) that consists of an exatecan derivative (e.g., T-DXd) due to treatment-related toxicities.
- •Clinically active brain metastases, spinal cord compression, or leptomeningeal carcinomatosis, defined as untreated or symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms.
- •Inadequate treatment washout period before enrollment as specified in the protocol.
- •Any history of interstitial lung disease (ILD)/pneumonitis, current ILD, or suspicion of ILD.
研究组 & 干预措施
Cohort 1: Endometrial Cancer (EC)
Participants with recurrent or metastatic EC who were previously treated with 1 or more systemic therapy will receive I-DXd, 12 milligrams per kilogram (mg/kg), intravenous (IV) infusion.
干预措施: Ifinatamab deruxtecan (Drug)
Cohort 2: Head and Neck Squamous Cell Carcinoma (HNSCC)
Participants with recurrent or metastatic HNSCC who were previously treated with 1 or more systemic therapy will receive I-DXd, 12 mg/kg, IV infusion.
干预措施: Ifinatamab deruxtecan (Drug)
Cohort 3: Pancreatic Ductal Adenocarcinoma (PDAC)
Participants with recurrent or metastatic PDAC who were previously treated with 1 or more systemic therapy will receive I-DXd, 12 mg/kg, IV infusion.
干预措施: Ifinatamab deruxtecan (Drug)
Cohort 4: Colorectal Cancer (CRC)
Participants with recurrent or metastatic CRC who were previously treated with 1 or more systemic therapy will receive I-DXd, 12 mg/kg, IV infusion.
干预措施: Ifinatamab deruxtecan (Drug)
Cohort 5: Hepatocellular Carcinoma (HCC)
Participants with recurrent or metastatic HCC who were previously treated with 1 or more systemic therapy will receive I-DXd, at the determined dose.
干预措施: Ifinatamab deruxtecan (Drug)
Cohort 6: Adenocarcinoma of esophagus, gastroesophageal junction, and stomach (Ad-Eso/GEJ/gastric)
Participants with recurrent or metastatic Ad-Eso/GEJ/gastric who were previously treated with 1 or more systemic therapy will receive I-DXd, 12 mg/kg, IV infusion.
干预措施: Ifinatamab deruxtecan (Drug)
Cohort 7: Urothelial Carcinoma (UC)
Participants with recurrent or metastatic UC who were previously treated with 1 or more systemic therapy will receive I-DXd, 12 mg/kg, IV infusion.
干预措施: Ifinatamab deruxtecan (Drug)
Cohort 8: Ovarian Cancer (OVC)
Participants with recurrent or metastatic non-squamous OVC who were previously treated with 1 or more systemic therapy will receive I-DXd, 12 mg/kg, IV infusion.
干预措施: Ifinatamab deruxtecan (Drug)
Cohort 9: Cervical Cancer (CC)
Participants with recurrent or metastatic CC who were previously treated with 1 or more systemic therapy will receive I-DXd, 12 mg/kg, IV infusion.
干预措施: Ifinatamab deruxtecan (Drug)
Cohort 10: Biliary Tract Cancer (BTC)
Participants with recurrent or metastatic BTC who were previously treated with 1 or more systemic therapy will receive I-DXd, 12 mg/kg, IV infusion.
干预措施: Ifinatamab deruxtecan (Drug)
Cohort 11: Human epidermal growth factor 2 (HER2)-low breast cancer (BC)
Participants with recurrent or metastatic human epidermal growth factor 2 (HER2)-low BC who were previously treated with 1 or more systemic therapy will receive I-DXd, 12 mg/kg, IV infusion.
干预措施: Ifinatamab deruxtecan (Drug)
Cohort 12: HER2 Immunohistochemistry (IHC) 0 BC
Participants with recurrent or metastatic HER2 IHC 0 BC who were previously treated with 1 or more systemic therapy will receive I-DXd, 12 mg/kg, IV infusion.
干预措施: Ifinatamab deruxtecan (Drug)
Cohort 13: Cutaneous Melanoma
Participants with recurrent or metastatic cutaneous melanoma who were previously treated with 1 or more systemic therapy will receive I-DXd, 12 mg/kg, IV infusion.
干预措施: Ifinatamab deruxtecan (Drug)
Cohort 14: Neuroendocrine Carcinoma (NEC)
Participants with recurrent or metastatic NEC who were previously treated with 1 or more systemic therapy or for whom the standard therapy is not considered appropriate by the investigator will receive I-DXd, 12 mg/kg, IV infusion.
干预措施: Ifinatamab deruxtecan (Drug)
结局指标
主要结局
Number of Participants Reporting Treatment-emergent Adverse Events and Death in the HCC Cohort
时间窗: From date of signing the informed consent form up to 47 days after the last dose of study drug , up to approximately 57 months
A TEAE is defined as an adverse event (AE) with a start or worsening date during the on-treatment period. AEs will be coded using MedDRA and will be graded using NCI-CTCAE v5.0.
Number of Participants Reporting Dose-limiting Toxicities in the HCC Cohort
时间窗: Cycle 1 Day 1 to Cycle 1 Day 21
A dose-limiting toxicity (DLT) is defined as any treatment-emergent adverse event (TEAE) not attributable to disease or disease-related processes that occurs during the DLT evaluation period (from C1D1 to the end of Cycle 1 in Safety Run-in) and is Grade 3 or above, according to NCI-CTCAE version 5.0, with the exceptions as noted in the protocol.
Objective Response Rate (ORR) as Assessed by Investigator
时间窗: From the time of the first dose of study drug until the date of documented disease progression, death, loss to follow-up, or withdrawal by the subject, whichever occurs first up to approximately 57 months
ORR is defined as the proportion of participants with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) as assessed by Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Objective Response Rate (ORR) as Assessed by Investigator
时间窗: From the time of the first dose of study drug until the date of documented disease progression, death, loss to follow-up, or withdrawal by the subject, whichever occurs first (up to approximately 60 months)
ORR is defined as the percentage of participants with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) as assessed by Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Number of Participants Reporting Dose-limiting Toxicities (DLTs) in the HCC Cohort
时间窗: Cycle 1 Day 1 to Cycle 1 Day 21
A DLT is defined as any treatment-emergent adverse event (TEAE) not attributable to disease or disease-related processes that occurs during the DLT evaluation period (from C1D1 to the end of Cycle 1 in Safety Run-in) and is Grade 3 or above, according to NCI-CTCAE version 5.0, with the exceptions as noted in the protocol.
Number of Participants Reporting TEAEs and Death in the HCC Cohort
时间窗: From date of signing the informed consent form up to 47 days after the last dose of study drug, up to approximately 60 months
An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. TEAEs are defined as those AEs with start or worsening after the first dose date of I-DXd and up to 40 (+7) days after the last dose date of study drug.
次要结局
- Percentage of Participants Who Have Treatment-emergent ADA(Baseline up to 57 months)
- Progression-free Survival (PFS)(From the time of the first dose of study drug until the date of documented disease progression, death, loss to follow-up, or withdrawal by the subject, whichever occurs first, up to approximately 57 months)
- Pharmacokinetic Parameter Half-life (t1/2) for I DXd, total anti-B7-H3 antibody, and DXd(Cycles 1 and 3 Day 1: predose, end of infusion, 3 hours (hr), 6 hr; 24 hr, 168 hr; 336 hr; 504 hr; Cycles 2, 4, and 5 Day 1: predose and end of infusion; Cycle 7 and every 2 cycles thereafter up to EOS (57 months) predose (every cycle is 21 days))
- Duration of Response (DoR)(From the time of the first dose of study drug until the date of documented disease progression (confirmed by investigator), death, loss to follow-up, or withdrawal by the subject, whichever occurs first, up to approximately 57 months)
- Disease Control Rate (DCR)(From the time of the first dose of study drug until the date of documented disease progression (by investigator), death, loss to follow-up, or withdrawal by the subject, whichever occurs first, up to approximately 57 months)
- Pharmacokinetic Parameter Minimum Concentration (Ctrough) for I DXd, total anti-B7-H3 antibody, and DXd(Cycles 1 and 3 Day 1: predose, end of infusion, 3 hours (hr), 6 hr; 24 hr, 168 hr; 336 hr; 504 hr; Cycles 2, 4, and 5 Day 1: predose and end of infusion; Cycle 7 and every 2 cycles thereafter up to EOS (57 months) predose (every cycle is 21 days))
- Pharmacokinetic Parameter Time to Reach Maximum Plasma Concentration (TMax) for I DXd, total anti-B7-H3 antibody, and DXd(Cycles 1 and 3 Day 1: predose, end of infusion, 3 hours (hr), 6 hr; 24 hr, 168 hr; 336 hr; 504 hr; Cycles 2, 4, and 5 Day 1: predose and end of infusion; Cycle 7 and every 2 cycles thereafter up to EOS (57 months) predose (every cycle is 21 days))
- Incidence of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs)(From date of signing the informed consent form up to 47 days after the last dose of study drug , up to approximately 57 months)
- Pharmacokinetic Parameter Maximum Concentration (CMax) for I DXd, total anti-B7-H3 antibody, and DXd(Cycles 1 and 3 Day 1: predose, end of infusion, 3 hours (hr), 6 hr; 24 hr, 168 hr; 336 hr; 504 hr; Cycles 2, 4, and 5 Day 1: predose and end of infusion; Cycle 7 and every 2 cycles thereafter up to EOS (57 months) predose (every cycle is 21 days))
- Pharmacokinetic Parameter Area Under the Curve (AUC) for I DXd, total anti-B7-H3 antibody, and DXd(Cycles 1 and 3 Day 1: predose, end of infusion, 3 hours (hr), 6 hr; 24 hr, 168 hr; 336 hr; 504 hr; Cycles 2, 4, and 5 Day 1: predose and end of infusion; Cycle 7 and every 2 cycles thereafter up to EOS (57 months) predose (every cycle is 21 days))
- Overall Survival (OS)(From the date of the first dose of drug up to the date of death due to any cause, up to approximately 57 months)
- Percentage of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline)(Baseline up to 57 months)
- Incidence of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs)(From date of signing the informed consent form up to 47 days after the last dose of study drug, up to approximately 60 months)
- Duration of Response (DoR)(From the time of the first dose of study drug until the date of documented disease progression, death, loss to follow-up, or withdrawal by the subject, whichever occurs first, up to approximately 60 months)
- Progression-free Survival (PFS)(From the time of the first dose of study drug until the date of documented disease progression, death, loss to follow-up, or withdrawal by the subject, whichever occurs first, up to approximately 60 months)
- Disease Control Rate (DCR)(From the time of the first dose of study drug until the date of documented disease progression (by investigator), death, loss to follow-up, or withdrawal by the subject, whichever occurs first, up to approximately 60 months)
- Overall Survival (OS)(From the date of the first dose of drug up to the date of death due to any cause, up to approximately 60 months)
- Pharmacokinetic Parameter Maximum Concentration (CMax) for I DXd, total anti-B7-H3 antibody, and DXd(Cycles1 & 3 Day1:pre-dose,end of infusion(EOI),post-dose at 3 hours(hr),6 hr;24 hr,168 hr;336 hr;504 hr; Cycles 2, 4, and 5 Day 1:pre-dose and EOI;Cycle 7 and every 2 cycles thereafter up to end of study(EOS)(60 months):pre-dose(every cycle is 21 days)])
- Pharmacokinetic Parameter Time to Reach Maximum Plasma Concentration (TMax) for I DXd, total anti-B7-H3 antibody, and DXd(Cycles 1 and 3 Day 1: pre-dose, EOI, 3 hr, 6 hr; 24 hr, 168 hr; 336 hr; 504 hr; Cycles 2, 4, and 5 Day 1: pre-dose and EOI; Cycle 7 and every 2 cycles thereafter up to EOS (60 months): pre-dose (every cycle is 21 days)])
- Pharmacokinetic Parameter Half-life (t1/2) for I DXd, total anti-B7-H3 antibody, and DXd(Cycles 1 and 3 Day 1: pre-dose, EOI, 3 hr, 6 hr; 24 hr, 168 hr; 336 hr; 504 hr; Cycles 2, 4, and 5 Day 1: pre-dose and EOI; Cycle 7 and every 2 cycles thereafter up to EOS (60 months): pre-dose (every cycle is 21 days)])
- Pharmacokinetic Parameter Minimum Concentration (Ctrough) for I DXd, total anti-B7-H3 antibody, and DXd(Cycles 1 and 3 Day 1: pre-dose, EOI, 3 hr, 6 hr; 24 hr, 168 hr; 336 hr; 504 hr; Cycles 2, 4, and 5 Day 1: pre-dose and EOI; Cycle 7 and every 2 cycles thereafter up to EOS (60 months): pre-dose (every cycle is 21 days)])
- Pharmacokinetic Parameter Area Under the Curve (AUC) for I DXd, total anti-B7-H3 antibody, and DXd(Cycles 1 and 3 Day 1: pre-dose, EOI, 3 hr, 6 hr; 24 hr, 168 hr; 336 hr; 504 hr; Cycles 2, 4, and 5 Day 1: pre-dose and EOI; Cycle 7 and every 2 cycles thereafter up to EOS (60 months): pre-dose (every cycle is 21 days)])
- Percentage of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline)(Baseline up to 60 months)
- Percentage of Participants Who Have Treatment-emergent ADA(Baseline up to 60 months)