Clinical trial NCT06362252: 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)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Extensive Stage-small Cell Lung Cancer
Keywords: Extensive stage-small cell lung cancer (ES-SCLC)
Ifinatamab deruxtecan
I-DXd
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2024-04-12
Enrollment: 123
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

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

Inclusion Criteria

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

1. Sign and date the informed consent form (ICF), prior to the start of any study-specific qualification procedures.
2. Adults ≥18 years or the minimum legal adult age (whichever is greater) at the time the ICF is signed.
3. Has histologically or cytologically confirmed diagnosis of ES-SCLC who will require first-line (IL) therapy.
4. 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.
5. 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.
6. 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.
7. Has ECOG PS of ≤1 (assessed within 7 days before enrollment/randomization).
8. Has adequate organ and bone marrow function within 7 days before the start of study treatment as specified in the study protocol.
9. A female subject of childbearing potential (POCBP) is eligible to participate if the following conditions are met:

   1. Subject is not pregnant as confirmed by highly sensitive pregnancy test during Screening (within 3 days prior to enrollment/randomization)
   2. 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.
   3. 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.
10. 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.

    1. Avoid donating sperm.
    2. 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.
11. Is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.

Exclusion Criteria

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

1. Has received prior treatment with orlotamab, enoblituzumab, or other B7-H3 targeted agents, including I-DXd.
2. Prior discontinuation of an ADC that consists of an exatecan derivative (eg, trastuzumab deruxtecan) due to treatment-related toxicities.
3. 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.
4. Has inadequate washout period before enrollment/randomization as specified in the study protocol.
5. Has any of the following within the past 6 months: cerebrovascular accident, transient ischemic attack, or another arterial thromboembolic event.
6. 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.
7. Has clinically significant corneal disease.
8. Has uncontrolled or significant cardiovascular disease,.
9. 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.
10. Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
11. 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.
12. 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.
13. Has history of allogeneic bone marrow, stem cell, or solid organ transplant.
14. 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.
15. Has history of hypersensitivity to the drug substances, inactive ingredients in the drug product or severe hypersensitivity reactions to other monoclonal antibodies.
16. Has evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection.
17. Has active or uncontrolled human immunodeficiency virus (HIV) infection.
18. Has active or uncontrolled hepatitis B or C virus (HBV or HCV) infection.
19. Has history of autoimmune disease.
20. Has any evidence of severe or uncontrolled systemic diseases.
21. Has received a live vaccine within 30 days prior to the first dose of study drug.
22. Is a female who is pregnant or breastfeeding or planning to become pregnant.
23. 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.
24. Has psychological, social, familial, or logistical factors that would prevent regular follow-up

Primary outcomes:
measure: Number of Participants Reporting Dose-limiting Toxicities Following I-DXd in Combination With Atezolizumab With or Without Carboplatin (Part A)
timeFrame: Cycle 1 Day 1 up to Cycle 1 Day 21 (each cycle is 21 days)
measure: Overall Number of Participants With Treatment-emergent Adverse Events Following I-DXd in Combination With Atezolizumab With or Without Carboplatin (Part A and B)
timeFrame: Baseline up to 37 months
Secondary outcomes:
measure: 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)
timeFrame: 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
measure: 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)
timeFrame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 37 months
measure: 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)
timeFrame: 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
measure: 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)
timeFrame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 37 months
measure: 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)
timeFrame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 37 months
measure: 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)
timeFrame: 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
measure: 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)
timeFrame: Baseline up to approximately 37 months
measure: Overall Survival Following I-DXd in Combination With Atezolizumab With or Without Carboplatin (Part A and B)
timeFrame: From the start date of study drug to the date of death due to any cause, whichever occurs first, up to approximately 37 months
measure: Pharmacokinetic Parameter Maximum Serum Concentration of I-DXd
timeFrame: 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)
measure: Pharmacokinetic Parameter Time to Maximum Serum Concentration of I-DXd
timeFrame: 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)
measure: Pharmacokinetic Parameter Area Under the Concentration Curve of I-DXd
timeFrame: 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)
measure: The Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive At Any Time and Who Have A Treatment-emergent Anti-Drug Antibody
timeFrame: Baseline up to approximately 37 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama -Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: David Geffen School of Medicine
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic-Jacksonville
state: Florida
city: Orlando
country: United States
facility: Advent Health Orlando
state: Florida
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center of Northwestern University
state: Illinois
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Regents of the University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: East Brunswick
country: United States
facility: Astera Cancer Care
state: New Jersey
city: Hackensack
country: United States
facility: John Theurer Cancer Center At Hackensack Umc
state: New Jersey
city: Mineola
country: United States
facility: New York University Cancer Center - Laura and Isaac Perlmutter Cancer Center At Nyu Langone
state: New York
city: Mineola
country: United States
facility: NYU Langone Hospital - Long Island
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Columbia University Hervert Irving Comprehensive Cancer Center
state: New York
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital - Central
state: Pennsylvania
city: Nashville
country: United States
facility: Scri Oncology Partners
state: Tennessee
city: Fairfax
country: United States
facility: Next Virginia
state: Virginia
city: Vancouver
country: United States
facility: Northwest Cancer Specialists, P.C.-Vancouver
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Lille Cedex
country: France
facility: Hopital Albert Calmette - Chu Lille
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Assistance Publique-Hă"Pitaux de Marseille
city: Paris Cedex 05
country: France
facility: Institut Curie - Site de Paris
city: Paris
country: France
facility: Hopital Tenon
city: Rennes cedex 09
country: France
facility: Chu Rennes - Hopital Pontchaillou
city: Saint Herblain
country: France
facility: Chu Nantes - Hă"Pital Guillaume Et Renă Laă<Nnec
city: Suresnes Cedex
country: France
facility: Hă"Pital Foch
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Hirakata-shi
country: Japan
facility: Kansai Medical University Hospital
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
city: Koto-ku
country: Japan
facility: The Cancer Institute Hospital of Jfcr
city: Kumamoto
country: Japan
facility: Social Welfare Organization Saiseikai Imperial Gift Foundation, Inc. Saiseikai Kumamoto Hospital
city: Nagaizumi-cho
country: Japan
facility: Shizuoka Cancer Center
city: Niigata
country: Japan
facility: Niigata Cancer Center Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka-Sayama
country: Japan
facility: Kindai University Hospital
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall D'Hebron
city: Girona
country: Spain
facility: Ico Girona - Hospital Universitari de Girona Dr Josep Trueta
city: L'Hospitalet de Llobregat
country: Spain
facility: Ico L'Hospitalet - Hospital Duran I Reynals
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario Ramon Y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Next Madrid
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
city: Vigo
country: Spain
facility: Hospital Alvaro Cunqueiro
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: