A Study of Patritumab Deruxtecan in Pediatric Participants With Relapsed or Refractory Solid Tumors (MK-9999-01C/LIGHTBEAM-U01)

Official title

LIGHTBEAM-U01 Substudy 01C: A Phase 1/2 Substudy to Evaluate the Safety and Efficacy of Patritumab Deruxtecan in Pediatric Participants With Relapsed or Refractory Solid Tumors

Overview

Researchers are looking for new ways to treat children with hepatoblastoma or rhabdomyosarcoma (RMS) that has relapsed or is refractory: * Hepatoblastoma is a common liver cancer in babies and very young children * RMS is a cancer that starts in muscle cells, often in a child's head and neck, bladder, arms, or legs * Relapsed means the cancer came back after treatment * Refractory means the cancer did not respond (get smaller or go away) to treatment The study treatment HER3-DXd (also known as MK-1022 or patritumab deruxtecan) is an antibody-drug conjugate (ADC). An ADC attaches to a protein on cancer cells and delivers treatment to destroy those cells. The goals of this study are to learn: * About the safety of HER3-DXd in children and if they tolerate it * What happens to HER3-DXd in children's bodies over time * If children who receive HER3-DXd have the cancer get smaller or go away

Detailed description

This study will have 2 parts: a safety lead-in to demonstrate a tolerable safety profile and confirm a preliminary recommended phase 2 dose (RP2D) (Part 1) followed by an efficacy evaluation (Part 2)

Interventions

• Biological Patritumab Deruxtecan
  IV Infusion

Primary outcome measures

• Part 1: Percentage of Participants Who Experience Dose-limiting Toxicities (DLTs) [Time frame: Cycle 1 (up to approximately 21 days); each cycle is 21 days]
• Part 1: Percentage of Participants Who Experience an Adverse Event (AE) [Time frame: Up to approximately 5 years]
• Part 1: Percentage of Participants Who Discontinue Study Treatment Due to an AE [Time frame: Up to approximately 5 years]
• Part 1: Area Under the Curve (AUC) of total anti-HER3 antibody liquid chromatography-mass spectrometry (LC-MS) in plasma [Time frame: At designated timepoints (up to approximately 5 years)]
• Part 1: AUC of anti-HER3 antibody-conjugated DXd (anti-HER3-ac-DXd) in plasma [Time frame: At designated timepoints (up to approximately 5 years)]
• Part 1: AUC of DXd in plasma [Time frame: At designated timepoints (up to approximately 5 years)]
• Part 1: Maximum Concentration (Cmax) of anti-HER3 antibody LC-MS in plasma [Time frame: At designated timepoints (up to approximately 5 years)]
• Part 1: Cmax of anti-HER3-ac-DXd in plasma [Time frame: At designated timepoints (up to approximately 5 years)]
• Part 1: Cmax of DXd in plasma [Time frame: At designated timepoints (up to approximately 5 years)]
• Part 1: Concentration Immediately Before the Next Dose is Administered (Ctrough) of anti-HER3 antibody LC-MS in plasma [Time frame: At designated timepoints (up to approximately 5 years)]

Secondary outcome measures (12)

• Part 2: Percentage of Participants Who Experience an AE [Time frame: Up to approximately 5 years]
• Part 2: Percentage of Participants Who Discontinue Study Treatment Due to an AE [Time frame: Up to approximately 5 years]
• Part 1 and Part 2: Disease Control Rate (DCR) [Time frame: Up to approximately 5 years]
• Part 1 and Part 2: Time to Response (TTR) [Time frame: Up to approximately 5 years]
• Part 1 and Part 2: Duration of Response (DOR) [Time frame: Up to approximately 5 years]
• Part 1 and Part 2: Progression-free Survival (PFS) [Time frame: Up to approximately 5 years]
• Part 1 and Part 2: Overall Survival (OS) [Time frame: Up to approximately 5 years]
• Part 2: AUC of total anti-HER3 antibody LC-MS in plasma [Time frame: At designated timepoints (up to approximately 5 years)]
• Part 2: AUC of anti-HER3-ac-DXd in plasma [Time frame: At designated timepoints (up to approximately 5 years)]
• Part 2: AUC of DXd in plasma [Time frame: At designated timepoints (up to approximately 5 years)]
• Part 2: Cmax of anti-HER3 antibody LC-MS in plasma [Time frame: At designated timepoints (up to approximately 5 years)]
• Part 2: Cmax of anti-HER3-ac-DXd in plasma [Time frame: At designated timepoints (up to approximately 5 years)]

Eligibility criteria

The main inclusion criteria include but are not limited to the following:

• Has one of the following histologically confirmed advanced or metastatic solid tumors: Rhabdomyosarcoma (RMS), or Hepatoblastoma
• Has progressed after at least 1 prior systemic treatment for RMS or hepatoblastoma and who has no satisfactory alternative treatment option (ie, is ineligible for other standard treatment regimens)
• Participants who have adverse events (AEs) due to previous anticancer therapies must have recovered to Grade ≤1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have Grade ≤2 neuropathy are eligible. Participants with Grade ≤2 alopecia are also eligible
• Hepatitis B surface antigen (HBsAg) positive participants are eligible if they have received hepatitis B virus (HBV) antiviral therapy and have undetectable HBV viral load
• Participants with a history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable

The main exclusion criteria include but are not limited to the following:

• Has a history of interstitial lung disease (ILD)/pneumonitis irrespective of steroid use, or current ILD/pneumonitis, or suspected ILD/pneumonitis, or ILD that cannot be ruled out by imaging
• Has clinically severe respiratory compromise resulting from intercurrent pulmonary illness
• Has a history of solid organ transplant
• Has a history of allogeneic stem cell transplant
• Has clinically significant corneal disease
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis/leptomeningeal disease; participants with previously treated brain metastases may participate provided they are radiologically stable (ie, without evidence of progression) for at least 4 weeks
• Has uncontrolled or significant cardiovascular disorder
• Has a history of clinically significant congenital cardiac syndrome
• Has a history of human immunodeficiency virus (HIV) infection
• Has a known additional malignancy that is progressing or has required active treatment within the past 1 year
• Has an active infection requiring systemic therapy
• Has concurrent active hepatitis B (HBsAg positive and/or detectable HBV deoxyribonucleic acid \[DNA\]) and HCV defined as anti-HCV antibody (Ab) positive and detectable HCV ribonucleic acid \[RNA\]) infection
• Has not adequately recovered from major surgery or have ongoing surgical complications

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 17 centers

• Childrens Hospital Los Angeles ( Site 3006) — Los Angeles
• Children's Hospital Colorado-Center for Cancer and Blood Disorders ( Site 3016) — Aurora
• Yale New Haven Hospital ( Site 3012) — New Haven
• Johns Hopkins All Children's Hospital ( Site 3025) — St. Petersburg
• University of Iowa Health Care Holden Comprehensive Cancer Center ( Site 3017) — Iowa City
• Dana-Farber Cancer Institute ( Site 3013) — Boston
• Corewell Health ( Site 3001) — Grand Rapids
• Children's Mercy Hospital ( Site 3024) — Kansas City
• … and 9 more centers

France · 5 centers

• Bordeaux University Hospital - Pellegrin ( Site 3105) — Bordeaux
• Assistance Publique Hôpitaux de Marseille - Hôpital de la Timone ( Site 3102) — Marseille
• Centre Hospitalier Universitaire de Nantes - Hôpital Femme-Enfant-Adolescent Chu De Nantes — Nantes
• Centre Leon-Berard ( Site 3100) — Lyon
• Institut Curie ( Site 3101) — Paris

United Kingdom · 4 centers

• Birmingham Children's Hospital ( Site 3349) — Birmingham
• Royal Victoria Infirmary ( Site 3348) — Newcastle upon Tyne
• University Hospital of Wales ( Site 3346) — Cardiff
• Royal Marsden Hospital ( Site 3347) — Sutton

Australia · 3 centers

• Sydney Children's Hospital-Kids Cancer Centre ( Site 3997) — Sydney
• Queensland Children's Hospital ( Site 3996) — Brisbane
• Royal Children's Hospital ( Site 3994) — Parkville

Brazil · 3 centers

• Hospital de Clinicas de Porto Alegre ( Site 3265) — Porto Alegre
• Fundação Pio XII - Hospital de Câncer de Barretos ( Site 3264) — Barretos
• Fundação Faculdade Regional de Medicina de São José do Rio Preto ( Site 3267) — São José do Rio Preto

Colombia · 3 centers

• Hospital Pablo Tobon Uribe ( Site 3923) — Medellín
• Clinica de la Costa S.A.S. ( Site 3924) — Barranquilla
• IMAT S.A.S ( Site 3921) — Montería

Italy · 3 centers

• Fondazione IRCCS Istituto Nazionale dei Tumori ( Site 3552) — Milan
• Ospedale Pediatrico Bambino Gesù IRCCS ( Site 3553) — Roma
• Ospedale Infantile Regina Margherita ( Site 3551) — Torino

Spain · 3 centers

• Hospital Sant Joan de Déu ( Site 3717) — Esplugues de Llobregat
• Hospital Universitari Vall d''Hebron ( Site 3716) — Barcelona
• Hospital Infantil Universitario Nino Jesus ( Site 3715) — Madrid

Turkey (Türkiye) · 3 centers

• Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 3961) — Ankara
• Ankara Bilkent Şehir Hastanesi. ( Site 3962) — Ankara
• Ege Universitesi Hastanesi ( Site 3963) — Izmir

Canada · 2 centers

• Alberta Children's Hospital ( Site 3227) — Calgary
• The Hospital for Sick Children ( Site 3225) — Toronto

Czechia · 2 centers

• Detska nemocnice FN Brno ( Site 3388) — Brno
• Fakultni nemocnice v Motole-Klinika detske hematologie a onkologie ( Site 3387) — Prague

Germany · 2 centers

• UniversitaetsklInikum Tuebingen ( Site 3142) — Tübingen
• Universitätsklinikum Münster - Albert Schweitzer Campus ( Site 3141) — Münster

Israel · 2 centers

• Rambam Health Care Campus ( Site 3674) — Haifa
• Sheba Medical Center ( Site 3675) — Ramat Gan

South Korea · 2 centers

• Seoul National University Hospital-Pediatrics ( Site 3972) — Seoul
• Asan Medical Center-Pediatrics - Pedicatric Oncology ( Site 3973) — Seoul

Belgium · 1 center

• UZ Gent ( Site 3428) — Ghent

Chile · 1 center

• Hospital Carlos Van Buren ( Site 3880) — Valparaíso

Denmark · 1 center

• Rigshospitalet-Department of paediatrics and adolescent medicine, Section of Paed haem-onc — Copenhagen

Greece · 1 center

• Aghia Sophia Children's Hospital-First Department of Pediatrics, National and Kapodistrian — Athens

Hungary · 1 center

• Semmelweis University ( Site 3838) — Budapest

Netherlands · 1 center

• Prinses Maxima Centrum voor Kinderoncologie ( Site 3510) — Utrecht

Slovakia · 1 center

• Narodny ustav detskych chorob ( Site 3592) — Bratislava

Sweden · 1 center

• Sahlgrenska Universitetssjukhuset ( Site 3634) — Gothenburg

Taiwan · 1 center

• National Taiwan University Hospital ( Site 3983) — Taiwan

Identifiers

NCT: NCT06941272 · 9999-01C · MK-9999-01C · LIGHTBEAM-U01 · U1111-1314-1866 · 2024-518771-66-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗