A Study of Ifinatamab Deruxtecan Versus Treatment of Physician's Choice in Subjects With Relapsed Small Cell Lung Cancer

Small Cell Lung Cancer Clinical Trial

— IDeate-Lung02  

Official title:

A Phase 3, Multicenter, Randomized, Open-label Study of Ifinatamab Deruxtecan (I-DXd), a B7-H3 Antibody Drug Conjugate (ADC), Versus Treatment of Physician's Choice (TPC) in Subjects With Relapsed Small Cell Lung Cancer (SCLC) (IDeate-Lung02)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06203210
• Other study ID #: DS7300-188
• Secondary ID: 2023-509628-16
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: June 10, 2024
• Est. completion date: February 22, 2029

Study information

• Verified date: April 2024
• Source: Daiichi Sankyo
• Contact: Daiichi Sankyo Contact for Clinical Trial Information
• Phone: 9089926400
• Email: CTRinfo[@]dsi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study was designed to compare the efficacy and safety of I-DXd with treatment of physician's choice in participants with relapsed small cell lung cancer (SCLC).

Description:

The primary objective of this study is to assess whether treatment with I-DXd improves objective response rate (ORR) and prolongs overall survival (OS) compared with treatment of physician's choice among participants with relapsed SCLC. The secondary objectives of the study are to further evaluate the efficacy/safety of I-DXd, health economics and outcome research measures (including patient reported outcomes), immunogenicity of I-DXd, B7-H3 protein expression, and characterize the pharmacokinetics of I-DXd.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 468
• Est. completion date: February 22, 2029
• Est. primary completion date: April 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria Participants must meet all the following criteria to be eligible for randomization into the

study:

1. Sign and date the informed consent form 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 informed consent form is signed.

3. Has histologically or cytologically documented SCLC.

4. The participant must provide adequate baseline tumor samples with sufficient quantity and quality of tumor tissue content.

5. Has received prior therapy with only one prior platinum-based line as systemic therapy for SCLC with at least 2 cycles of therapy and a chemotherapy-free interval of >30 days.

6. Has at least 1 measurable lesion according to RECIST v1.1 as assessed by the investigator.

7. Has documentation of radiological disease progression on or after the most recent systemic therapy.

8. Has ECOG PS of =1.

9. Subjects with untreated and asymptomatic brain metastases or subjects with treated brain metastases that are no longer symptomatic (ie, without neurologic signs or symptoms) and who require no treatment with steroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. Subjects must have a stable neurologic status for at least 2 weeks prior to the first dose of study drug. 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 humanized anti-B7 homologue 3 (B7-H3) targeted agents, including I-DXd.

2. Prior discontinuation of an antibody drug conjugate (ADC) that consists of an exatecan derivative (eg, trastuzumab deruxtecan) due to treatment-related toxicities.

3. Has received any of the comparators used in this study or any topoisomerase I inhibitor.

4. Has inadequate washout period before randomization as specified in the protocol.

5. Has any of the following conditions within the past 6 months: cerebrovascular accident, transient ischemic attack, or another arterial thromboembolic event.

6. Has uncontrolled or significant cardiovascular disease.

7. Has clinically significant corneal disease.

8. Has history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required corticosteroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at Screening.

9. Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses, including, but not limited to, any underlying pulmonary disorder and potential pulmonary involvement caused by any autoimmune, connective tissue, or inflammatory disorders, prior pneumonectomy, or requirement for supplemental oxygen.

Related Conditions & MeSH terms

• Lung Neoplasms
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma

Intervention

Drug:
• Ifinatamab deruxtecan
12 mg/kg intravenous dose on Day 1 of each 21-day cycle
• Topotecan
Topotecan will be administered per local SoC.
• Amrubicin
Amrubicin will be administered per local SoC.
• Lurbinectedin
Lurbinectedin will be administered per local SoC

Locations

Country	Name	City	State
Australia	Ballarat Base Hospital	Ballarat
Australia	Chris Oâ Brien Lifehouse	Camperdown
Australia	Sunshine Hospital	St Albans
Australia	St John of God Subiaco Hospital	Subiaco
Australia	Townsville Cancer Centre	Townsville
Australia	Princess Alexandra Hospital	Woolloongabba
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	UZA	Edegem
Belgium	Jessa Ziekenhuis Hospital	Hasselt
Belgium	Chu de Lia Ge	Liege
Belgium	AZ DELTA	Roeselare
Belgium	Chu Ucl Namur	Yvoir
Brazil	Hospital de Ca'Ncer de Barretos - Fundaa A O Pio Xii	Barretos
Brazil	Cepon - Centro de Pesquisas Oncola"Gicas de Santa Catarina	FlorianAlpolis
Brazil	Clínica de Neoplasias Litoral Ltda.	ItajaA-
Brazil	Hospital São Lucas Da Pucrs	Porto Alegre
Brazil	A. C. Camargo Cancer Center	SALo Paulo
Brazil	Hospital Benefica Ncia Portuguesa de Sa O Paulo	SALo Paulo
Brazil	Hospital Sirio-Libanes	SALo Paulo
Brazil	Icesp - Instituto Do Câncer Do Estado de São Paulo Octavio Frias de Oliveira	SALo Paulo
Brazil	Cepho - Centro de Estudos E Pesquisas de Hematologia E Oncologia	Santo Andre
Brazil	Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto	Sao Jose Rio Preto
Canada	Queen Elizabeth Ii Health Sciences Centre	Halifax
Canada	Princess Margaret Cancer Center	Toronto
China	Beijing Cancer Hospital	Beijing
China	Beijing Chest Hospital,Capital Medical University	Beijing
China	Jilin Province Tumor Hospital	Changchun
China	Hunan Cancer Hospital	Changsha
China	Sichuan Cancer Hospital	Chengdu
China	West China Hospital, Sichuan University	Chengdu
China	Chongqing University Cancer Hospital	Chongqing
China	The First Affiliated Hospital, College of Medicine, Zhejiang University	Hangzhou
China	Zhejiang Cancer Hospital	Hangzhou
China	Harbin Medical University Cancer Hospital	Harbin
China	Shandong Cancer Hospital	Jinan
China	Linyi Cancer Hospital	Linyi
China	The Second Peoples Hospital of Neijiang	Neijiang
China	Fudan University Shanghai Cancer Center	Shanghai
China	Tianjin Medical University Cancer Institute & Hospital	Tianjin
China	The Affiliated Cancer Hospital of Xinjiang Medical University	Urumqi
China	Hubei Cancer Hospital	Wuhan
China	Union Hospital of Tongji Medical College, Huazhong University of Science and Technology	Wuhan
China	The First Affiliated Hospital of Xiâ An Jiaotong University	Xi'an
China	Xiangyang Central Hospital	Xiangyang
China	Yantai Yuhuangding Hospital	Yantai
China	Henan Cancer Hospital	Zhengzhou
France	Institut Sainte Catherine	Avignon Cedex 9
France	Chu Bordeaux	Bordeaux cedex
France	Centre Hospitalier Intercommunal de Cra Teil	Creteil Cedex
France	Hopital Albert Calmette - Chu Lille	Lille Cedex
France	Chu Limoges - Hopital Du Cluzeau	Limoges cedex
France	Centre Léon Bérard	Lyon
France	Assistance Publique-Ha"Pitaux de Marseille	Marseille
France	Institut Régional Du Cancer de Montpellier	Montpellier
France	Hopital Arnaud de Villeneuve	Montpellier cedex 05
France	Ch de Mulhouse - Ha"Pital Emile Muller	Mulhouse Cedex
France	Hopital Tenon	Paris
France	Institut Curie - Site de Paris	Paris Cedex 05
France	Chu Rennes - Hopital Pontchaillou	Rennes cedex 09
France	Chu Nantes - Ha"Pital Guillaume Et Rena Laa<Nnec	Saint Herblain
France	Institut de Cancerologie de La Loire	Saint-Priest-En-Jarez
France	Ha"Pital Foch	Suresnes Cedex
France	Institut Gustave Roussy	Villejuif cedex
Germany	Evangelische Lungenklinik Berlin	Berlin
Germany	Helios Klinikum Erfurt	Erfurt
Germany	Universtitaetsklinikum Essen	Essen
Germany	Krankenhaus Nordwest Gmbh	Frankfurt
Germany	Universitaetsklinikum Frankfurt Goethe-Universitaet	Frankfurt am Main
Germany	Asklepios Fachkliniken Muenchen-Gauting	Gauting
Germany	Srh Wald-Klinikum Gera Gmbh	Gera
Germany	Universitaetsklinikum Giessen Und Marburg Gmbh Standort Giessen	Giessen
Germany	Asklepios Klinik Harburg	Hamburg
Germany	Lki Lungenfachklinik Immenhausen	Immenhausen/Krs. Kassel
Germany	Staedtisches Krankenhaus Kiel	Kiel
Germany	Johannes Wesling Klinikum Minden	Minden
Germany	Pius-Hospital Oldenburg	Oldenburg
Germany	Universitaetsklinikum Ulm	Ulm
Hungary	Orszagos Koranyi Pulmonologiai Intezet	Budapest
Hungary	Orszagos Onkologiai Intezet	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Gyor-Moson-Sopron Varmegyei Petz Aladar Egyetemi Oktato Korhaz	Gyor
Hungary	Bacs-Kiskun Varmegyei Oktatokorhaz	Kecskemet
Italy	Istituto Tumori Giovanni Paolo Ii Irccs Ospedale Oncologico Bari	Bari
Italy	Humanitas Gavazzeni	Bergamo
Italy	Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia (Presidio Spedali Civili)	Brescia
Italy	Azienda Ospedaliera Universitaria Policlinico - Vittorio Emanuele (Presidio Gaspare Rodolico)	Catania
Italy	Azienda Ospedaliero Universitaria Mater Domini	Catanzaro
Italy	Istituto Nazionale Per La Ricerca Sul Cancro Di Genova	Genova
Italy	Fondazione Irccs Istituto Nazionale Dei Tumori	Milano
Italy	Ieo Istituto Europeo Di Oncologia	Milano
Italy	Ospedale San Raffaele	Milano
Italy	Azienda Socio Sanitaria Territoriale Di Monza (Presidio San Gerardo)	Monza
Italy	Azienda Ospedaliera Universitaria- Universita Degli Studi Della Campania  Luigi Vanvitelliâ	Napoli
Italy	Azienda Ospedaliero Universitaria Di Parma	Parma
Italy	Azienda Ospedaliera Di Perugia Ospedale S. Maria Della Misericordia	Perugia
Italy	Istituto Nazionale Tumori Regina Elena Irccs	Roma
Italy	Istituto Clinico Humanitas	Rozzano
Italy	Centro Ricerche Cliniche Di Verona S.R.L.	Verona
Japan	National Cancer Center Hospital	Chuo-ku
Japan	Kyushu University Hospital	Fukuoka
Japan	National Cancer Center Hospital East	Kashiwa
Japan	The Cancer Institute Hospital of Jfcr	Koto-ku
Japan	National Hospital Organization Shikoku Cancer Center	Matsuyama
Japan	Okayama University Hospital	Okayama
Japan	Kindai University Hospital	Osaka-Sayama
Japan	Kitasato University Hospital	Sagamihara
Japan	National Hospital Organization Hokkaido Cancer Center	Sapporo
Japan	Shizuoka Cancer Center	Sunto-gun
Japan	Osaka Medical and Pharmaceutical University Hospital	Takatsuki
Japan	Wakayama Medical University Hospital	Wakayama
Korea, Republic of	Chungbuk National University Hospital	Cheongju
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu
Korea, Republic of	National Cancer Center	Goyan-si
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	The Catholic University of Korea, St. Vincent'S Hospital	Suwon-si
Netherlands	Jeroen Bosch Ziekenhuis	's Hertogenbosch
Netherlands	Netherlands Cancer Institute	Amsterdam
Netherlands	Maastricht University Medical Center	Maastricht
Netherlands	Etz Elisabeth	Tilburg
Poland	Krakowski Szpital Specjalistyczny Im. Jana Pawla Ii	Krakow
Poland	Mazowieckie Centrum Leczenia Chorob Pluc I Gruzlicy	Otwock
Poland	Szpital Specjalistyczny W Prabutach	Prabuty
Poland	Provita Prolife	Tomaszow Mazowiecki
Portugal	Centro Hospitalar E Universita Rio de Coimbra E.P.E.	Coimbra
Portugal	Hospital Da Senhora Da Oliveira Guimara Es	Guimarães
Portugal	Centro Hospitalar de Lisboa Norte, E.P.E. - Hospital Pulido Valente	Lisboa
Portugal	Hospital Da Luz	Lisboa
Romania	Institutul Oncologic 'Prof. Dr. Ion Chiricuta' Cluj Napoca	Cluj Napoca
Romania	S.C Radiotherapy Center Cluj S.R.L	Comuna Floresti
Romania	S.C Centrul de Oncologie Sfantul Nectarie Craiova	Craiova
Romania	S.C. Sigmedical Services Srl	Suceava
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital de La Santa Creu I Sant Pau	Barcelona
Spain	Hospital Universitari Vall D'Hebron	Barcelona
Spain	Hospital Universitario Reina Sofia	Cordoba
Spain	Hospital Universitario Ciudad de Jaen	Jaen
Spain	Hospital de Especialidades de Jerez de La Frontera	Jerez De Frontera
Spain	Ico L'Hospitalet - Hospital Duran I Reynals	L'Hospitalet de Llobregat
Spain	Complejo Hospitalario Universitario Insular Materno-Infantil	Las Palmas de Gran Canaria
Spain	Hospital Regional Universitario de Malaga	MAAlaga
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Universitario Ramon Y Cajal	Madrid
Spain	Hospital Universitario Virgen Del Rocio	Sevilla
Spain	Hospital Universitario Virgen Macarena	Sevilla
Switzerland	Inselspital - Universitaetsspital Bern	Bern
Switzerland	Hfr Fribourg/Kantonsspital Fribourg	Fribourg
Switzerland	Kantonsspital St. Gallen	St. Gallen
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung City
Taiwan	China Medical University Hospital	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Cheng Kung University Hospitalx	Tainan
Taiwan	National Taiwan University Cancer Centre	Taipei
Taiwan	Taipei Medical University Hospital	Taipei
Taiwan	Chang Gung Memorial Hospital	Taoyuan County
Taiwan	Taipei Veterans General Hospital	Tapei
Turkey	Ankara City Hospital	Ankara
Turkey	Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital	Ankara
Turkey	Dicle University, Medical Faculty	Diyarbakir
Turkey	Goztepe Prof. Dr. Suleyman Yalcin City Hospital	Istanbul
Turkey	Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty	Istanbul
Turkey	Medipol University Medical Faculty	Istanbul
Turkey	Izmir Medicalpark Hospital	Izmir
United Kingdom	Birmingham Heartlands Hospital	Birmingham
United Kingdom	St James'S University Hospital	Leeds
United Kingdom	The Christie	Manchester
United Kingdom	Churchill Hospital	Oxford
United States	John Hopkins School of Medicine	Baltimore	Maryland
United States	University of Maryland Medical Group	Baltimore	Maryland
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Montefiore Medical Center Prime	Bronx	New York
United States	Mercy Medical Center	Canton	Ohio
United States	Rush University Medical Center	Chicago	Illinois
United States	Henry Ford Health System	Detroit	Michigan
United States	Duke University Health System	Durham	North Carolina
United States	Astera Cancer Care	East Brunswick	New Jersey
United States	Providence Medical Foundation	Fullerton	California
United States	The West Clinic	Germantown	Tennessee
United States	Houston Methodist Cancer Center	Houston	Texas
United States	University of Texas Md Anderson Cancer Center	Houston	Texas
United States	Clinical Research Alliance, Inc	Lake Success	New York
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Baptist Health Lexington	Lexington	Kentucky
United States	David Geffen School of Medicine	Los Angeles	California
United States	University of Miami Hospital and Clinics Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	New York University Cancer Center - Laura and Isaac Perlmutter Cancer Center At Nyu Langone	Mineola	New York
United States	Meridian Health Systems	Neptune	New Jersey
United States	Nebraska Educational Biomedical Research Association	Omaha	Nebraska
United States	Adventhealth Cancer Insitute	Orlando	Florida
United States	Providence Portland Medical Center	Portland	Oregon
United States	Mercy Clinic Oncology and Hematology Sindelar Cancer Center	Saint Louis	Missouri
United States	Highlands Oncology Group	Springdale	Arkansas
United States	H. Lee Moffitt Cancer Center and Research Institute, Inc	Tampa	Florida
United States	Texas Oncology, P.A. - Tyler	Tyler	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Daiichi Sankyo	Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Canada,  China,  France,  Germany,  Hungary,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Portugal,  Romania,  Spain,  Switzerland,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Objective Response Rate Assessed by Blinded Independent Central Review	Confirmed objective response rate (ORR) is defined as the sum of the complete response (CR) rate and partial response (PR) rate based on BICR by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.	Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 4.5 years
Primary	Overall Survival		From the date of randomization to the date of death due to any cause, whichever occurs first, up to approximately 4.5 years
Secondary	Number of Participants With Objective Response Rate Assessed by Investigator	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.	Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 4.5 years
Secondary	Progression-free Survival As Assessed by Blinded Independent Central Review and Investigator	PFS is defined as the time interval from the date of randomization to the date of disease progression as per BICR and investigator assessment or death due to any cause.	Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 4.5 years
Secondary	Duration of Response As Assessed by Blinded Independent Central Review and Investigator	Duration of response (DoR) is defined as the time from the date of the first documentation of objective response (complete response [CR] or partial response [PR]) to the date of the first documentation of progressive disease (PD) or death. The DoR will be calculated for responding participants (PR or CR) only.	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 4.5 years
Secondary	Disease Control Rate As Assessed by Blinded Independent Central Review and Investigator	Disease control rate is defined as the proportion of participants who have achieved a best overall response of confirmed CR, confirmed PR, or SD (or non-CR/non-PD) by BICR and investigator assessment per RECIST v1.1.	Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 4.5 years
Secondary	Time to Response As Assessed by Blinded Independent Central Review and Investigator	TTR is defined as the time from the date of randomization to the first documentation of objective tumor response (CR or PR) that is subsequently confirmed by BICR and investigator assessment .Time to response (TTR) will be calculated for confirmed responders only.	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 4.5 years
Secondary	Change from Baseline in The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30	This 30-item questionnaire assesses global health status (GHS)/quality of life (QoL), subject functioning, and general cancer symptoms and has a recall period of one week. All scores for the EORTC QLQ-C30 instrument are linearly transformed to a 0 to 100 metric, where a higher score on GHS/QoL and functioning scales indicates a better outcome and a higher score for the symptom scales indicates worse outcomes.	Baseline up to 4.5 years
Secondary	Change from Baseline in The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer 29 (EORTC QLQ-LC29)	The LC29 is a self-reported 29-item questionnaire that measures SCLC-related symptoms and the side effects of treatments and has a recall period of one week. All scores range from 0 to 100, with a higher score indicating a worse outcome.	Baseline up to 4.5 years
Secondary	Overall Number of Participants With Treatment-emergent Adverse Events Following I-DXd Monotherapy	TEAEs are assessed based on NCI CTCAE v5.0.	Baseline up to 4.5 years
Secondary	The Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive At Any Time and Who Have A Treatment-emergent Anti-Drug Antibody	The ADA prevalence, which is the percentage of participants who are ADA positive at any time point (baseline or post-baseline), as well as the ADA incidence, which is the proportion of participants having treatment-emergent ADA during the study period, will only be reported in participants receiving I-DXd.	Baseline up to 4.5 years
Secondary	Pharmacokinetic Parameter Maximum Concentration for I-DXd, Total Anti-B7-H3 Antibody, and MAAA-1181a	Maximum concentration (Cmax) will be assessed using non-compartmental methods in participants randomized to the I-DXd group.	Cycle 1 before infusion (BI), end of infusion EOI), and 3, 6, 24, 72, 168, 336, and 504 hours (hrs) post dose; Cycle 2 BI and EOI; Cycle 3 BI, EOI, and 6 hrs postdose; Cycles 4, 5, and every 2 cycles thereafter up to 4.5 years BI (each cycle is 21 days)
Secondary	Pharmacokinetic Parameter Time to Maximum Concentration for I-DXd, Total Anti-B7-H3 Antibody, and MAAA-1181a	Time to maximum concentration (Tmax) will be assessed using non-compartmental methods in participants randomized to the I-DXd group.	Cycle 1 before infusion (BI), end of infusion EOI), and 3, 6, 24, 72, 168, 336, and 504 hours (hrs) post dose; Cycle 2 BI and EOI; Cycle 3 BI, EOI, and 6 hrs postdose; Cycles 4, 5, and every 2 cycles thereafter up to 4.5 years BI (each cycle is 21 days)
Secondary	Pharmacokinetic Parameter Area Under the Plasma Concentration-Time Curve for I-DXd, Total Anti-B7-H3 Antibody, and MAAA-1181a	Area under the plasma concentration-time curve up to the last quantifiable time point (AUClast) and area under the plasma concentration-time curve dosing interval (AUCtau) will be assessed using non-compartmental methods in participants randomized to the I-DXd group.	Cycle 1 before infusion (BI), end of infusion EOI), and 3, 6, 24, 72, 168, 336, and 504 hours (hrs) post dose; Cycle 2 BI and EOI; Cycle 3 BI, EOI, and 6 hrs postdose; Cycles 4, 5, and every 2 cycles thereafter up to 4.5 years BI (each cycle is 21 days)