A Study of I-DXd in Combination With Atezolizumab With or Without Carboplatin as First-Line Induction or Maintenance in Subjects With Extensive Stage-Small Cell Lung Cancer (IDeate-Lung03)

Официальное название

A Phase 1b/2, Multicenter, Open-label Study of Ifinatamab Deruxtecan (I-DXd), a B7-H3 Antibody-Drug Conjugate (ADC), in Combination With Atezolizumab With or Without Carboplatin as First-line Induction or Maintenance, in Subjects With Extensive-stage Small Cell Lung Cancer (ES-SCLC) (IDeate-Lung03)

Обзор

This study is designed to evaluate the safety and efficacy of ifinatamab deruxtecan (I-DXd) in combination with immune checkpoint inhibitor (ICI) atezolizumab with or without carboplatin in participants with extensive stage-small cell lung cancer (ES-SCLC) in the first-line (1L) setting.

Подробное описание

This study consists of two parts and two cohorts: Part A (Phase 1b; Safety Run-in) and Part B (Phase 2; Dose Optimization), Cohort 1 (I-DXd in maintenance) and Cohort 2 (I-DXd in induction + maintenance).

The primary objective of this study is to evaluate the safety and tolerability of I-DXd in combination with atezolizumab with or without carboplatin by assessing treatment-emergent adverse events (TEAEs) and other safety parameters which will inform optimal dose selection of I-DXd in the combination regimens (Dose Optimization Part B) of this study.

Вмешательства

• Препарат Ifinatamab deruxtecan
  Intravenous administration
• Препарат Atezolizumab
  Intravenous administration
• Препарат Carboplatin
  Intravenous administration

Первичные конечные точки

• Number of Participants Reporting Dose-limiting Toxicities Following I-DXd in Combination With Atezolizumab With or Without Carboplatin (Part A) [Срок оценки: Cycle 1 Day 1 up to Cycle 1 Day 21 (each cycle is 21 days)]
• Overall Number of Participants With Treatment-emergent Adverse Events Following I-DXd in Combination With Atezolizumab With or Without Carboplatin (Part A and B) [Срок оценки: Baseline up to 37 months]

Вторичные конечные точки (12)

• Progression-free Survival As Assessed by Blinded Independent Central Review and Investigator Following I-DXd in Combination With Atezolizumab With or Without Carboplatin (Part A and B) [Срок оценки: From start date of study drug to the earlier date of the first objective documentation of radiographic disease progression assessed by BICR and investigator per RECIST v1.1 or death due to any cause, whichever occurs first, up to approximately 37 months]
• Objective Response Rate Assessed by Blinded Independent Central Review and Investigator Following I-DXd in Combination With Atezolizumab With Carboplatin (Part A and B of Cohort 2 Only) [Срок оценки: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 37 months]
• Duration of Response As Assessed by Blinded Independent Central Review and Investigator Following I-DXd in Combination With Atezolizumab With Carboplatin (Part A and B of Cohort 2 Only) [Срок оценки: 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 37 months]
• Disease Control Rate As Assessed by Blinded Independent Central Review and Investigator Following I-DXd in Combination With Atezolizumab With Carboplatin (Part A and B of Cohort 2 Only) [Срок оценки: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 37 months]
• Clinical Benefit Rate as Assessed by Blinded Independent Central Review and Investigator Following I-DXd in Combination With Atezolizumab With Carboplatin (Part A and B of Cohort 2 Only) [Срок оценки: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 37 months]
• Time to Response As Assessed by Blinded Independent Central Review and Investigator Following I-DXd in Combination With Atezolizumab With Carboplatin (Part A and B of Cohort 2 Only) [Срок оценки: 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 37 months]
• Best Percentage Change in the Sum of Diameters (SoD) of Measurable Tumors As Assessed by Blinded Independent Central Review and Investigator Following I-DXd in Combination With Atezolizumab With Carboplatin (Part A and B of Cohort 2 Only) [Срок оценки: Baseline up to approximately 37 months]
• Overall Survival Following I-DXd in Combination With Atezolizumab With or Without Carboplatin (Part A and B) [Срок оценки: From the start date of study drug to the date of death due to any cause, whichever occurs first, up to approximately 37 months]
• Pharmacokinetic Parameter Maximum Serum Concentration of I-DXd [Срок оценки: Cycle 1 Day 1 pre-dose up to Cycle 9 (and every 2 cycles thereafter up to 37 months) Day 1 pre-dose (each cycle is 21 days)]
• Pharmacokinetic Parameter Time to Maximum Serum Concentration of I-DXd [Срок оценки: Cycle 1 Day 1 pre-dose up to Cycle 9 (and every 2 cycles thereafter up to 37 months) Day 1 pre-dose (each cycle is 21 days)]
• Pharmacokinetic Parameter Area Under the Concentration Curve of I-DXd [Срок оценки: Cycle 1 Day 1 pre-dose up to Cycle 9 (and every 2 cycles thereafter up to 37 months) Day 1 pre-dose (each cycle is 21 days)]
• The Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive At Any Time and Who Have A Treatment-emergent Anti-Drug Antibody [Срок оценки: Baseline up to approximately 37 months]

Критерии участия

A full list of inclusion/exclusion criteria are available in the protocol.

Критерии включения

Participants must meet all of the following criteria to be eligible for enrollment into the study:

• Sign and date the informed consent form (ICF), prior to the start of any study-specific qualification procedures.
• Adults ≥18 years or the minimum legal adult age (whichever is greater) at the time the ICF is signed.
• Has histologically or cytologically confirmed diagnosis of ES-SCLC who will require first-line (IL) therapy.
• For Cohort 1, participant has received 4 cycles of 1L induction therapy with carboplatin, etoposide, and atezolizumab for ES-SCLC with ongoing CR PR, CR, or SD per RECIST v1.1 assessed by the investigator.

For Cohort 2, participant has received no prior treatment for ES-SCLC.

• For Cohort 2, participant has at least one measurable lesion according to RECIST v1.1 on computed tomography (CT) or magnetic resonance imaging (MRI) as assessed by the investigator.
• For Cohort 2, participant must have at least one lesion, amenable to core biopsy, and must consent to provide a pretreatment biopsy tissue sample and on-treatment biopsy.
• Has ECOG PS of ≤1 (assessed within 7 days before enrollment/randomization).
• Has adequate organ and bone marrow function within 7 days before the start of study treatment as specified in the study protocol.
• A female subject of childbearing potential (POCBP) is eligible to participate if the following conditions are met:

• Subject is not pregnant as confirmed by highly sensitive pregnancy test during Screening (within 3 days prior to enrollment/randomization)
• Subject does not breastfeed during the treatment period and for at least 8/5/6 months after last dose of I-DXd/atezolizumab/carboplatin, respectively.
• Subject agrees to adhere to a contraceptive method that is highly effective and agrees not to donate eggs (ova, oocytes) to others or freeze/store eggs during the treatment period and for at least the time needed to eliminate each study drug after the last dose. The length of time required to continue contraception and avoid donating/freezing eggs after last dose for I-DXd/atezolizumab/carboplatin is 8/5/6 months, respectively. Preservation of eggs may be considered prior to first dose of study drug.
• A male subject capable of producing sperm is eligible to participate if he agrees to the following during the intervention period and for at least the time needed to eliminate each study drug. The length of time required to continue contraception and avoid donating sperm after last dose for I-DXd/atezolizumab/carboplatin is 6/5/6 months, respectively.

• Avoid donating sperm.
• Adhere to either of the contraception methods: true abstinence from penile-vaginal intercourse or uses a penile/external condom when having penile-vaginal intercourse with a non-subject of childbearing potential plus partner use of an additional contraceptive method.
• Is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.

Критерии исключения

Participants who meet any of the following criteria will be disqualified from entering the study:

• Has received prior treatment with orlotamab, enoblituzumab, or other B7-H3 targeted agents, including I-DXd.
• Prior discontinuation of an ADC that consists of an exatecan derivative (eg, trastuzumab deruxtecan) due to treatment-related toxicities.
• Has received prior treatment with CD137 agonists or ICIs, including anti-cytotoxic T-cell lymphocyte-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, except for atezolizumab for Cohort 1.
• Has inadequate washout period before enrollment/randomization as specified in the study protocol.
• Has any of the following within the past 6 months: cerebrovascular accident, transient ischemic attack, or another arterial thromboembolic event.
• Has clinically active brain metastases, spinal cord compression, or leptomeningeal carcinomatosis, defined as untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms.
• Has clinically significant corneal disease.
• Has uncontrolled or significant cardiovascular disease,.
• Has history of (non-infectious) ILD/pneumonitis that required corticosteroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at Screening.
• Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
• Is on chronic steroid treatment (dose of 10 mg daily or more prednisone equivalent), except for low-dose inhaled steroids (for asthma/chronic obstructive pulmonary disease, topical steroids (for mild skin conditions), or intra-articular steroid injections.
• Has history of malignancy other than SCLC within the 5 years prior to randomization/enrollment, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, superficial gastrointestinal tract tumors, and non-muscle invasive bladder cancer curatively resected by endoscopic surgery.
• Has history of allogeneic bone marrow, stem cell, or solid organ transplant.
• Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE V5.0, Grade ≤1 or baseline.
• Has history of hypersensitivity to the drug substances, inactive ingredients in the drug product or severe hypersensitivity reactions to other monoclonal antibodies.
• Has evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection.
• Has active or uncontrolled human immunodeficiency virus (HIV) infection.
• Has active or uncontrolled hepatitis B or C virus (HBV or HCV) infection.
• Has history of autoimmune disease.
• Has any evidence of severe or uncontrolled systemic diseases.
• Has received a live vaccine within 30 days prior to the first dose of study drug.
• Is a female who is pregnant or breastfeeding or planning to become pregnant.
• Has prior or ongoing clinically relevant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the participant; alter the absorption, distribution, metabolism, or excretion of the study drug; or confound the assessment of study results.
• Has psychological, social, familial, or logistical factors that would prevent regular follow-up

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 26 центров

• University of Alabama -Birmingham — Birmingham
• Mayo Clinic Arizona — Phoenix
• David Geffen School of Medicine — Los Angeles
• Hoag Memorial Hospital Presbyterian — Newport Beach
• Mayo Clinic-Jacksonville — Jacksonville
• Advent Health Orlando — Orlando
• Moffitt Cancer Center — Tampa
• Robert H. Lurie Comprehensive Cancer Center of Northwestern University — Chicago
• … и ещё 18 центров

Испания · 12 центров

• Hospital Clinic de Barcelona — Barcelona
• Hospital Universitari Vall D'Hebron — Barcelona
• Ico Girona - Hospital Universitari de Girona Dr Josep Trueta — Girona
• ICO l'Hospitalet - Hospital Duran i Reynals — L'Hospitalet de Llobregat
• Hospital General Universitario Gregorio Marañon — Madrid
• Hospital Universitario Ramon Y Cajal — Madrid
• Hospital Universitario 12 de Octubre — Madrid
• Next Madrid — Madrid
• … и ещё 4 центра

Япония · 11 центров

• NHO Himeji Medical Center — Himeji-shi
• Kansai Medical University Hospital — Hirakata-shi
• National Cancer Center Hospital East — Kashiwa
• The Cancer Institute Hospital of Jfcr — Kōtoku
• Social Welfare Organization Saiseikai Imperial Gift Foundation, Inc. Saiseikai Kumamoto Ho — Kumamoto
• Shizuoka Cancer Center — Nagaizumi-cho
• Niigata Cancer Center Hospital — Niigata
• Okayama University Hospital — Okayama
• … и ещё 3 центра

Франция · 9 центров

• Hopital Albert Calmette - Chu Lille — Lille
• Centre Léon Bérard — Lyon
• Hôpital de la Timone — Marseille
• Institut Curie - Site de Paris — Paris
• Hopital Tenon — Paris
• Chu Rennes - Hopital Pontchaillou — Rennes
• CHU Nantes - Hôpital Guillaume et René Laënnec — Saint-Herblain
• Hôpital Foch — Suresnes
• … и ещё 1 центр

Идентификаторы

NCT: NCT06362252 · DS7300-189 · 2023-509629-36 · 2031240089

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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