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NCT06330064PHASE1, PHASE2Recruiting

A Study to Evaluate the Efficacy and Safety of Ifinatamab Deruxtecan (I-DXd) in Subjects With Recurrent or Metastatic Solid Tumors (IDeate-PanTumor02)

Daiichi Sankyo

Start Date

4/10/2024

Completion Date

7/25/2028

Summary

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).

Detailed Description

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.

Eligibility Criteria

Age Range: 18 years to No maximum

Participants must meet all of the following criteria to be included in the study: Common Inclusion Criteria for All Participants 1. 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. 2. Participants ages ≥18 years (follow local regulatory requirements if the legal age of consent for study participation is \>18 years). 3. 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. 4. 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. 5. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Additional Inclusion Criteria for EC Participants 1. Pathologically or cytologically documented EC of any histological carcinoma subtype or endometrial carcinosarcoma, irrespective of microsatellite instability or mismatch repair status. 2. 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 1. 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. 2. 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. 3. 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. 4. 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. 5. 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 1. Pathologically or cytologically documented unresectable or metastatic CRC with microsatellite stable status (MSS). 2. 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. 3. No prior treatment with topoisomerase I inhibitors, such as irinotecan or topotecan. Additional Inclusion Criteria for HCC Participants 1. 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. 2. 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. 3. Barcelona Clinic Liver Cancer (BCLC) Stage B or C. 4. Liver function status should be Child-Pugh (CP) Class A. 5. Albumin-Bilirubin (ALBI) Grade 1 within 7 days prior to the first dose of study drug. 6. 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 1. 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. 2. 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 1. 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. 2. 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. 1. At least 1 line of therapy should include enfortumab vedotin in countries where enfortumab vedotin is approved and available. 2. Perioperative systemic therapies will be counted as 1 line of therapy. 3. To meet inclusion criteria requirement of prior ICI-containing therapy, use in the perioperative or metastatic setting will suffice. 4. Participants with actionable target tumor mutation should have been previously treated with targeted therapy. 5. The same regimen administered twice in different disease settings will be counted as 1 line of prior therapy. Additional Inclusion Criteria for CC Participants 1. 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. 2. 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 1. 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. 2. 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. 3. Participant is not considered primary platinum refractory and has not progressed during platinum treatment or within 4 weeks after the completion of platinum treatment. 4. Participants with actionable target tumor mutation should have been previously treated with targeted therapy. Additional Inclusion Criteria for BTC Participants 1. Pathologically or cytologically documented unresectable or metastatic BTC (intra- or extrahepatic cholangiocarcinoma or gallbladder carcinoma). 2. Relapse or progression after at least 1 prior line of systemic therapy, or 2 prior lines of systemic therapy if the participant has an actionable target and has received targeted therapy. 3. Histological subtypes other than ampullary cancer, small cell cancer, lymphoma, sarcoma, neuroendocrine tumors, mixed tumor histology, and/or mucinous cystic neoplasms (Please note that the histological subtypes listed here are not allowed.) Additional Inclusion Criteria for HER2-Low BC Participants 1. Pathologically or cytologically documented unresectable or metastatic BC. 2. Low HER2 expression, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested), according to ASCO-CAP 2018 HER2 testing guidelines, based on most recent testing, regardless of hormonal status. 3. Progression on or after treatment with trastuzumab deruxtecan (T-DXd). 4. Relapse or progression after at least 2 and a maximum of 3 prior lines of systemic therapy. Participants with metastatic hormone receptor (HR)+ BC who have received endocrine-based therapy and have received at least 2 and a maximum of 3 prior lines of additional systemic therapy in the metastatic setting. Participants with actionable target tumor mutation should have been previously treated with targeted therapy. Additional Inclusion Criteria for HER2 IHC 0 BC Participants 1. Pathologically or cytologically documented unresectable or metastatic BC. 2. Negative for HER2 expression, defined as IHC 0 (ISH- or untested) according to ASCO-CAP 2018 HER2 testing guidelines, based on the most recent testing, regardless of hormonal status. 3. Relapse or progression after at least 2 and a maximum of 3 prior lines of systemic therapy. Participants with metastatic HR+ BC who have received endocrine-based therapy and have received at least 2 and a maximum of 3 prior lines of additional systemic therapy in the metastatic setting. Participants with actionable target tumor mutation should have been previously treated with targeted therapy. Additional Inclusion Criteria for Cutaneous (Acral and Non-acral) Melanoma Participants 1. Histologically or cytologically confirmed cutaneous (acral and non-acral) melanoma. 2. Disease progression while on or after having received treatment with ≥1 prior line of ICI based therapy. Prior anti-PD-(L)1 therapy in the adjuvant setting may be counted as 1 line if there is recurrence within 12 weeks of the last dose. If the subject had BRAF mutated melanoma or other actionable target tumor mutation, they must have had disease progression on targeted therapy as well. Additional Inclusion Criteria for NEC Participants 1. Histologically or cytologically confirmed NEC types other than neuroendocrine prostate cancer (NEPC), small cell lung cancer (SCLC), and Merkel Cell Carcinoma, as defined by WHO 2022. Participants must meet at least 1 of the following criteria: 1. Disease that is relapsed/refractory to standard systemic therapy OR 2. Disease for which standard therapy does not exist OR 3. Disease for which standard therapy is not considered appropriate by the investigator. 2. Participants with mixed histology of large-cell neuroendocrine carcinoma (LCNEC) and SCLC are eligible if the neuroendocrine component predominates and represents at least 50% of the overall tumor tissue. Exclusion Criteria: Participants who meet any of the following criteria will be disqualified from entering the study: 1. Prior treatment with orlotamab, enoblituzumab, or other 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 (e.g., T-DXd) due to treatment-related toxicities. 3. 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. 4. Inadequate treatment washout period before enrollment as specified in the protocol. 5. Any history of interstitial lung disease (ILD)/pneumonitis, current ILD, or suspicion of ILD.

Interventions

DRUG

Ifinatamab deruxtecan

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Conditions

Recurrent or Metastatic Solid Tumors

Locations

Valkyrie Clinical Trials

Los Angeles, California 90067

United States

Los Angeles Cancer Network

Los Angeles, California 91204

United States

Pih Health Hematology Medical Oncology

Whittier, California 90602

United States

Orchard Healthcare Research Inc

Skokie, Illinois 60077

United States

M Health Fairview University of Minnesota Medical Center

Minneapolis, Minnesota 55114

United States

NYU Langone Health

New York, New York 10016

United States

Icahn School of Medicine At Mount Sinai Prime

New York, New York 10029

United States

Clinical Research Alliance, Inc

Westbury, New York 11590

United States

White Plains Hospital

White Plains, New York 10601

United States

Erlanger Health, Inc

Chattanooga, Tennessee 37403

United States

The West Clinic

Germantown, Tennessee 38138

United States

SCRI Oncology Partners

Nashville, Tennessee 37203

United States

Texas Oncology - West Texas

Amarillo, Texas 79124

United States

Texas Oncology, P.A.

Dallas, Texas 75246

United States

Texas Oncology Gulf Coast

Pearland, Texas 77584

United States

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah 84112

United States

Virginia Cancer Specialists

Fairfax, Virginia 22031

United States

Wenatchee Valley Hospital and Clinics

Wenatchee, Washington 98801

United States

Centro de Investigaciones Medicas Mar Del Plata

Mar del Plata, Buenos Aires B7600FYK

Argentina

Hospital Aleman

Buenos Aires, Ciudad Autonoma Buenos Aires C1118AAT

Argentina

Hospital Sirio Libanes

Caba, Ciudad Autonoma Buenos Aires C1419GEP

Argentina

DIABAID

Buenos Aires, C1061ABD

Argentina

Centro Médico Austral

Ciudad Autonoma Buenos Aires, 1019

Argentina

Centro de Investigaciones Medicas y Desarrollo LC SRL LC Investigacion

Ciudad Autonoma Buenos Aires, C1113AAE

Argentina

Blacktown Hospital

Blacktown, New South Wales NSW 2148

Australia

St Vincent'S Hospital Sydney

Mount Kuring-Gai, New South Wales 2080

Australia

Genesiscare North Shore Oncology

St Leonards, New South Wales 2065

Australia

Princess Alexandra Hospital

Woolloongabba, Queensland 4102

Australia

St John of God Subiaco Hospital

Subiaco, Western Australia 6008

Australia

Cliniques Universitaires Saint-Luc

Brussels, 1200

Belgium

Grand Hospital de Charleroi

Charleroi, 6000

Belgium

Universitair Ziekenhuis Gent

Ghent, 9000

Belgium

Uz Leuven

Leuven, 3000

Belgium

Chu de Liăge

Liège, 4000

Belgium

Hospital de Clínicas de Porto Alegre

Porto Alegre, Rio Grande do Sul 90035-903

Brazil

Hospital São Lucas Da Pucrs

Porto Alegre, Rio Grande do Sul 90610-000

Brazil

Cepon - Centro de Pesquisas Oncolăgicas de Santa Catarina

Florianópolis, Santa Catarina 88034-000

Brazil

Hospital de Câncer de Barretos - Fundação Pio XII

Barretos, São Paulo 14784-400

Brazil

Centro de Pesquisas Clinicas da Fundação Doutor Amaral Carvalho

Jaú, São Paulo 17210-120

Brazil

Biocenter

Concepción, Biobio 4030000

Chile

Centro Del Cancer UC

Santiago, Santiago Metropolitan 8320000

Chile

Clinica Redsalud Vitacura

Santiago, Santiago Metropolitan 8320000

Chile

Ic La Serena Research

La Serena, 1720430

Chile

James Lind Centro de Investigacion Del Cancer

Temuco, 4800827

Chile

Centre Georges François Leclerc

Dijon, Cote dÝOr 21000

France

Hopital Saint Andre

Bordeaux, Gironde 33075

France

Institut Bergonié

Bordeaux, Gironde 33076

France

Institut Régional Du Cancer de Montpellier

Montpellier, Herault 34298

France

CRLCC Eugene Marquis

Rennes, Ille Et Vilaine 35042

France

Ico - Site René Gauducheau

Saint-Herblain, Loire Atlantique 44800

France

Institut Curie - Site de Paris

Paris, Paris 75005

France

Centre Léon Bérard

Lyon, Rhone 69008

France

GustaveRoussy DptPharmacie

Villejuif, Val De Marne 94805

France

Chu Besançon - Hôpital Jean Minjoz

Besançon, 25000

France

Institut Claudius Regaud

Toulouse, 31059

France

Universitaetsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg 69120

Germany

Slk-Kliniken Heilbronn Gmbh

Heilbronn, Baden-Wurttemberg 74078

Germany

Universitätsklinikum Münster, Medizinische Klinik A

Münster, North Rhine-Westphalia 48149

Germany

Univ der Johannes GutenbergU

Mainz, Rhineland-Palatinate 55131

Germany

Staedtisches Klinikum Dresden Standort Dresden-Friedrichstadt

Dresden, Saxony 01067

Germany

Universitäres Krebszentrum Leipzig UCCL, UKL AöR

Leipzig, Saxony 04103

Germany

Vivantes Klinikum Neukoelln

Berlin, 12351

Germany

Charită - Campus Charită Mitte

Berlin, 13353

Germany

St Vincent'S University Hospital

Dublin, Dublin D04 T6F4

Ireland

Cork University Hospital

Cork, T12DC4A

Ireland

Mater Misericordiae University Hospital

Dublin, D07 R2WY

Ireland

Tallaght University Hospital

Dublin, D24 NR0A

Ireland

University Hospital Galway

Galway, H91YR71

Ireland

Fondazione Del Piemonte Per L'Oncologia Irccs Candiolo

Candiolo, 10060

Italy

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133

Italy

Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)

Milan, 20162

Italy

Istituto Nazionale Tumori Fondazione G. Pascale

Naples, 80131

Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, 00168

Italy

Istituto Clinico Humanitas

Rozzano, 20089

Italy

Aichi Cancer Center Hospital

Nagoya, Aichi-ken 464-8681

Japan

National Cancer Center Hospital East

Kashiwa, Chiba 277-8577

Japan

National Hospital Organization Shikoku Cancer Center

Matsuyama, Ehime 791-0280

Japan

Kindai University Hospital

Ōsaka-sayama, Osaka 589-8511

Japan

Shizuoka Cancer Center

Nagaizumi-cho, Shizuoka 411-8777

Japan

National Cancer Center Hospital

Chuo-ku, Tokyo 104-0045

Japan

The Cancer Institute Hospital of Jfcr

Koto-ku, Tokyo 135-8550

Japan

Saitama Cancer Center

Saitama, 362-0806

Japan

Medical Care & Research Sa de Cv

Mérida, 97070

Mexico

Centro de Atenciăn E Investigaciăn Clănica En Oncologăa

Mérida, 97134

Mexico

Cryptex Investigacion Clinica S.A. de C.V.

México, 06100

Mexico

Amsterdam Umc, Locatie Vumc

Amsterdam, 1081 HV

Netherlands

Universitair Medisch Centrum Groningen

Groningen, 9713 GZ

Netherlands

Radboudumc Nijmegen

Nijmegen, 6525 GA

Netherlands

Erasmus Medisch Centrum

Rotterdam, 3015 GD

Netherlands

Umc Utrecht

Utrecht, 3584 CW

Netherlands

SPZOZ Szpital Uniwer w Krakowie

Krakow, 30-688

Poland

Instytut MSF Sp. z o.o.

Lodz, 90-302

Poland

MRUK-MED i Spółka z ograniczoną odpowiedzialnością

Rzeszów, 35-021

Poland

Mazowiecki Szpital Wojewodzki W Siedlcach Sp Z O O

Siedlce, 08-110

Poland

Aidport Sp Z O.O.

Skorzewo, 60-185

Poland

Instituto Portuguăs de Oncologia de Lisboa Francisco Gentil, Epe

Lisbon, 1099-023

Portugal

Fundação Champalimaud

Lisbon, 1400-038

Portugal

Centro Hospitalar Universitário de Lisboa Norte

Lisbon, 1649-035

Portugal

Centro Hospitalar Universitario de Santo Antonio

Porto, 4099-001

Portugal

Inst Portude Onco do Porto

Porto, 4200-072

Portugal

Hospital Universitari Vall D'Hebron

Barcelona, 08035

Spain

Hospital Clinic de Barcelona

Barcelona, 08036

Spain

ICO l'Hospitalet - Hospital Duran i Reynals

Barcelona, 08908

Spain

Hospital General Universitario Gregorio Marañon

Madrid, 28009

Spain

Hospital Clínico San Carlos

Madrid, 28040

Spain

Hospital Universitario 12 de Octubre

Madrid, 28041

Spain

Hospital Universitario La Paz

Madrid, 28046

Spain

Hospital Universitario Virgen Macarena

Seville, 41009

Spain

China Medical University Hospital

Taichung, 404327

Taiwan

National Cheng Kung University Hospitalx

Tainan, 70403

Taiwan

National Taiwan University Hospital

Taipei, 10002

Taiwan

Taipei Veterans General Hospital

Taipei, 11217

Taiwan

Koo Foundation Sun Yat-Sen cancer center

Taipei, 11259

Taiwan

Tri-Service General Hospital

Taipei, 11490

Taiwan

Medipol Mega University Hospital

Bağcılar, Istanbul 34214

Turkey (Türkiye)

Gulhane Training and Research Hospital

Ankara, 06010

Turkey (Türkiye)

Gazi University Medical Faculty

Ankara, 06560

Turkey (Türkiye)

Ankara City Hospital

Ankara, 06800

Turkey (Türkiye)

Ankara University Cebeci Hospital

Ankara, 6590

Turkey (Türkiye)

Izmir Medicalpark Hospital

Izmir, 35530

Turkey (Türkiye)