A Phase I/II trial of MK-3475 (pembrolizumab) in children’s solid tumors and lymphoma

Phase 1

• Conditions: Treatment of advanced melanoma or advanced, relapsed or refractory PD-L1 positive malignant solid tumor or lymphoma in children from 6 months to less than 18 years old.; MedDRA version: 19.0Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 100000004864; MedDRA version: 19.0Level: LLTClassification code 10053571Term: MelanomaSystem Organ Class: 100000004864; MedDRA version: 19.0Level: LLTClassification code 10025315Term: Lymphoma malignantSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-002950-38-IT
• Lead Sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-08-17
• Last Update Posted: 12 March 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 310

Inclusion Criteria

1. Be willing and able to provide written informed consent/assent for the trial. The subject may also provide consent/assent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.
2. Be between 6 months and less than 18 years of age on day of signing informed consent/assent.
3. Have histologically or cytologically-documented, locally-advanced, or metastatic solid malignancy that is incurable and has either (a) failed prior standard therapy, (b) for which no standard therapy exists, or (c) standard therapy is not considered appropriate by the patient and treating physician. There is no limit to the number of prior treatment regimens.
4. Be able to provide tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated (tumors progressing in a prior site of radiation are allowed for characterization, other exceptions may be considered after Sponsor consultation). Samples that require decalcification are not allowed.
5. Have either advanced melanoma or a PD-L1 positive advanced, relapsed or refractory solid tumor or lymphoma as determined by IHC in archival formal fixed paraffin embedded tumor (FFPET) or newly obtained biopsy. For this trial, tumor specimens with positive stroma or at least 1% of cells expressing PD-L1 by IHC will be defined as PD-L1 positive. (Subjects with PD-L1 negative tumors may be enolled in Part II of the trial in selet tumor types where preliminary response is observed)
6. Have measurable disease based on RECIST 1.1. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. Subjects with neuroblastoma who do not have measurable disease per RECIST 1.1 but have MIBG-positive evaluable disease may be enrolled.
7. Have a performance status as defined below:
• Lansky Play Scale =50 for children up to and including 16 years of age;
• Karnofsky score =50 for children > 16 years of age
•Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
8. Demonstrate adequate organ function
9.Female subject of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication.
10. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication.
11. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

Are the trial subjects under 18? yes
Number of subjects for this age range: 311
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Is currently participating and receiving study therapy in,or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
3. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to mAbs administered more than 4 weeks earlier.
4. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to a previously administered agent.
5. Has a known additional malignancy that is progressing or requires active treatment with limited exceptions.
6. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging [using the same imaging techniques for diagnosis and follow-up] for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. Patients with primary CNS tumors or metastases of primary CNS tumors are not excluded but must be neurologically stable (e.g. without a progression of neurologic symptoms or requiring systemic steroid therapy within last 2 weeks). Of note, subjects with tumors involving the brain stem are excluded from the study.
7. Has an active autoimmune disease that has required systemic treatment in past 2 years
8. Has evidence of interstitial lung disease.
9. Has an active infection requiring systemic therapy.
10. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
11. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
12. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
13. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti CTLA-4 therapies or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). Subjects with melanoma who previously received treatment with ipilimumab are not excluded.
14. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
15. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
16. Has received a live vaccine within 30 days of planned start of study therapy.
17. Has undergone prior allogeneic hematopoetic stem cell transplantation within the last

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified