A phase II trial of MK-3475 (pembrolizumab) in children and young adults with classical Hodgkin lymphoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

19 Sep 2019 → ongoing

Decision date (initial)

2023-11-21

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-504821-38-00

EudraCT number

2017-001123-53

WHO UTN

U1111-1289-8373

ClinicalTrials.gov

NCT03407144

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Diagnosis, Therapy, Pharmacodynamic, Pharmacogenetic, Pharmacogenomic, Pharmacokinetic

To evaluate the objective response rate (ORR) by International Working Group (IWG) criteria as assessed by blinded independent central review (BICR) [Cheson, B. D., et al 2007] of pembrolizumab in combination with chemotherapy in slow early responders (SERs) by risk group (low, high).

Secondary objectives 6

1. To evaluate the rate of Positron Emission Tomography (PET) negativity, 2-year event-free survival (EFS) from study enrollment by IWG criteria as assessed by BICR, and overall survival (OS) of pembrolizumab in combination with chemotherapy in SERs by risk group
2. To evaluate the exposure to radiation therapy (RT) and its associated toxicity in SERs by risk group
3. To evaluate the rate of PET negativity per investigator assessment in Group 1 participants after completing 2 cycles of ABVD induction
4. To evaluate the 3-year EFS per investigator assessment and OS in rapid early responders (RERs) by risk group
5. To evaluate serum thymus and activation-regulated chemokine (TARC) as a potential biomarker in SERs by risk group
6. To evaluate the safety of pembrolizumab in combination with chemotherapy in SERs by risk group

Conditions and MedDRA coding

Classical Hodgkin lymphoma in children and young adults

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001474-PIP02-16

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Group 1: Must have newly diagnosed, pathologically confirmed classical Hodgkin Lymphoma (cHL) at Stages IA, IB and IIA without bulky disease. Group 2: Must have newly diagnosed, pathologically confirmed cHL at Stages IIEB, IIIEA, IIIEB, IIIB, IVA and IVB
2. Has measurable disease per investigator assessment.
3. Male participants are eligible to participate if they agree to the following during the intervention period: refrain from donating sperm plus either be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent or must agree to use contraception per protocol unless confirmed to be azoospermic.
4. Female participants who are not pregnant or breastfeeding, and who are either not a woman of childbearing potential (WOCBP), or are a WOCBP who agrees to use approved contraception during the intervention period and for at least 120 days after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period.
5. Performance status: Lansky Play-Performance Scale ≥50 for children up to 16 years of age OR Karnofsky score ≥50 for participants ≥ 16 years of age
6. Has adequate organ function

Exclusion criteria 20

1. Has undergone solid organ transplant at any time, or prior allogeneic hematopoietic stem cell transplantation within the last 5 years
2. WOCBP who has a positive urine pregnancy test within 24 hours before the first dose of study treatment
3. Baseline left ventricular ejection fraction value <50% or shortening fraction of <27%
4. Has received prior therapy with an anti-Programmed Death (PD)-1, anti-Programmed Death-Ligand 1 (PD-L1), or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor or has previously participated in a MSD pembrolizumab (MK-3475) clinical study
5. Has received any prior systemic anti-cancer therapy, including investigational agents for current diagnosis before randomization
6. Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed
7. Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
8. Has a diagnosis of lymphocyte-predominant Hodgkin Lymphoma (HL)
9. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of pembrolizumab
10. Has a known additional malignancy that is progressing or requires active treatment within the past 3 years
11. Has radiographically detectable central nervous system metastases and/or carcinomatous meningitis as assessed by local site investigator at the time of diagnosis
12. Has severe hypersensitivity (≥Grade 3) to any study therapies including any excipients
13. An active autoimmune disease that has required systemic treatment in past 2 years
14. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
15. Has an active infection requiring systemic therapy
16. Has a known history of human immunodeficiency virus (HIV) infection
17. Has a known history of Hepatitis B or known active Hepatitis C virus infection
18. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
19. Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study
20. Participants who have not adequately recovered from major surgery or have ongoing surgical complications

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective Response Rate (ORR) in SER Participants By Risk Group (Low, High) as assessed by Blinded Independent Central Review (BICR)

Secondary endpoints 10

1. Rate of Positron Emission Tomography (PET) Scan Negativity in SER Participants By Risk Group (Low, High) After AVD (Doxorubicin, vinblastine and dacarbazine) or COPDAC-28 (cyclophosphamide, vincristine, prednisone, and dacarbazine) Chemotherapy
2. Event-Free Survival (EFS) in SER Participants By Risk Group (Low, High) as Assessed by BICR
3. Overall Survival (OS) in SER Participants By Risk Group (Low, High)
4. Exposure to Radiotherapy (RT) in SER Participants By Risk Group (Low, High)
5. Rate of PET Scan Negativity In Group 1 Participants After ABVD Induction Therapy
6. EFS in Rapid Early Responder (RER) Participants By Risk Group (Low, High) as Assessed by Investigator
7. OS in RER Participants By Risk Group (Low, High)
8. Serum Thymus and Activation-Regulated Chemokine (TARC) Levels in SER Participants By Risk Group (Low, High)
9. Number of SER Participants Experiencing an Adverse Event (AE) By Risk Group (Low, High)
10. Number of SER Participants Discontinuing Study Treatment Due to AEs By Risk Group (Low, High)

Investigational products

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

Test 10

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Pallavi Pillai

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Pallavi Pillai

Third parties 5

Locations

8 EU/EEA countries · 25 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 103 files

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

Application history

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