A clinical study of patritumab deruxtecan (HER3-DXd) in children with cancer (MK-9999-01C)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

1 Jul 2025 → ongoing

Decision date (initial)

2025-08-22

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Daiichi Sankyo, Inc · Merck Sharp & Dohme LLC

External identifiers

EU CT number

2024-518771-66-00

WHO UTN

U1111-1314-1866

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Dose response, Therapy, Efficacy, Pharmacokinetic

1. Part 1: To evaluate the safety and tolerability and to establish a preliminary RP2D of patritumab deruxtecan (HER3-DXd)
2. Part 1: To characterize the PK of HER3-DXd
3. Part 1 and Part 2: To evaluate the preliminary antitumor effect of HER3-DXd in terms of ORR according to RECIST 1.1 per investigator assessment by tumor type

Secondary objectives 4

1. Part 2: To evaluate the safety and tolerability of HER3-DXd
2. Part 1 and Part 2: To evaluate the preliminary antitumor effect of HER3-DXd in terms of DCR, TTR, DOR, and PFS according to RECIST 1.1 per investigator assessment by tumor type
3. Part 1 and Part 2: To evaluate OS by tumor type
4. Part 2: To characterize the PK of HER3-DXd

Conditions and MedDRA coding

Hepatoblastoma, Rhabdomyosarcoma

Regulatory references

Scientific advice from competent authorities

Central Committee On Research Involving Human Subjects

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Has one of the following histologically confirmed advanced or metastatic solid tumors: Rhabdomyosarcoma (RMS), or Hepatoblastoma
2. 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)
3. 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
4. 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
5. Participants with a history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable

Exclusion criteria 13

1. Has a history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that required steroids or has current ILD/pneumonitis, and/or suspected ILD/pneumonitis that cannot be ruled out by standard diagnostic assessments
2. Has clinically severe respiratory compromise resulting from intercurrent pulmonary illness
3. Has a history of solid organ transplant
4. Has a history of allogeneic stem cell transplant
5. Has clinically significant corneal disease
6. 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
7. Has uncontrolled or significant cardiovascular disorder
8. Has a history of clinically significant congenital cardiac syndrome
9. Has a history of human immunodeficiency virus (HIV) infection
10. Has a known additional malignancy that is progressing or has required active treatment within the past 1 year
11. Has an active infection requiring systemic therapy
12. 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
13. Has not adequately recovered from major surgery or have ongoing surgical complications

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 13

1. Part 1: Percentage of Participants Who Experience Dose-limiting Toxicities (DLTs)
2. Part 1: Percentage of Participants Who Experience an Adverse Event (AE)
3. Part 1: Percentage of Participants Who Discontinue Study Treatment Due to an AE
4. Part 1: Area Under the Curve (AUC) of total anti-HER3 antibody liquid chromatography-mass spectrometry (LC-MS) in plasma
5. Part 1: AUC of anti-HER3 antibody-conjugated DXd (anti-HER3-ac-DXd) in plasma
6. Part 1: AUC of DXd in plasma
7. Part 1: Maximum Concentration (Cmax) of anti-HER3 antibody LC-MS in plasma
8. Part 1: Cmax of anti-HER3-ac-DXd in plasma
9. Part 1: Cmax of DXd in plasma
10. Part 1: Concentration Immediately Before the Next Dose is Administered (Ctrough) of anti-HER3 antibody LC-MS in plasma
11. Part 1: Ctrough of anti-HER3-ac-DXd
12. Part 1: Ctrough of DXd in plasma
13. Part 1 and Part 2: Objective Response Rate (ORR)

Secondary endpoints 16

1. Part 2: Percentage of Participants Who Experience an AE
2. Part 2: Percentage of Participants Who Discontinue Study Treatment Due to an AE
3. Part 1 and Part 2: Disease Control Rate (DCR)
4. Part 1 and Part 2: Time to Response (TTR)
5. Part 1 and Part 2: Duration of Response (DOR)
6. Part 1 and Part 2: Progressive-free Survival (PFS)
7. Part 1 and Part 2: Overall Survival (OS)
8. Part 2: AUC of total anti-HER3 antibody LC-MS in plasma
9. Part 2: AUC of anti-HER3-ac-DXd in plasma
10. Part 2: AUC of DXd in plasma
11. Part 2: Cmax of anti-HER3 antibody LC-MS in plasma
12. Part 2: Cmax of anti-HER3-ac-DXd in plasma
13. Part 2: Cmax of DXd in plasma
14. Part 2: Ctrough of anti-HER3 antibody LC-MS in plasma
15. Part 2: Ctrough of anti-HER3-ac-DXd in plasma
16. Part 2: Ctrough of DXd in plasma

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue, P. O. Box 2000 P. O. Box 2000

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Sama Ahsan

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Sama Ahsan

Third parties 8

Locations

12 EU/EEA countries · 27 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 158 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

16 submissions — initial application plus substantial / non-substantial modifications