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MK-4280

AcronymISRCTNEudraCTClinicaltrials.govDRKS
2018-001461-16

A Phase 1b Clinical Study to Evaluate the Safety and Efficacy of a Combination of MK-4280 and Pembrolizumab (MK-3475) in Participants with Hematologic Malignancies

Status: Active

Purpose / Objectives

Primary Outcome

  • To determine the safety and tolerability and to establish a preliminary RPTD of MK-4280 in combination with pembrolizumab in participants with PD-1/L1-naive R/R cHL, PD-1/L1-refractory R/R cHL, R/R DLBCL, or R/R-iNHL.

Secondary Outcomes

  • Within each disease type, to evaluate ORR of MK-4280 in combination with pembrolizumab as assessed by the investigator using the Revised Response Criteria for Malignant Lymphoma criteria {03QY3L}.
  • To evaluate the PK of MK-4280 administered via infusion in combination with pembrolizumab
  • To evaluate the PK of pembrolizumab administered via infusion in combination with MK-4280

Diagnosis

  • PD-1/L1-naive, relapsed or refractory classical Hodgkin lymphoma (PD-1/L1-naive R/R cHL; Cohort 1)
  • PD-1/L1-refractory, relapsed or refractory classical Hodgkin lymphoma (PD-1/L1-refractory R/R cHL; Cohort 2)
  • Relapsed or refractory DLBCL (R/R DLBCL; Cohort 3),
  • Relapsed or refractory indolent lymphoma (R/R -iNHL), with at least 10 participants in the R/R-iNHL group having follicular lymphoma (FL) (Cohort 4)

Patient attributes

Age

18-99

Inclusion criteria

Participants are eligible to be included in the study only if all of the following criteria apply:

  • Must have measureable disease, defined as at least 1 lesion that can be accurately measured in at least 2 dimensions with spiral CT scan. Minimum measurement must be >15 mm in the longest diameter or > 10 mm in the short axis.
  • Be able to provide a core or excisional tumor biopsy for biomarker analysis from an archival or newly obtained biopsy (within 3 months) at Screening.
  • [...]

Exclusion criteria

Participants are excluded from the study if any of the following criteria apply:

 Medical Conditions

1. Has known clinically active central nervous system involvement.

2. Has a known additional malignancy that is progressing or requires active treatment. (Exceptions: Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer undergone potentially curative therapy.

3. Has active autoimmune disease that has required systemic treatment in past 2 years. Replacement therapy is not considered a form of systemic treatment and is allowed.

4. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.

5. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.

6. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the pre-screening or screening visit through 120 days after the last dose of study intervention.

7. Has an active infection requiring intravenous systemic therapy.

8. Has known current symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.

9. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority. Refer to Appendix 7 for Germany-specific requirements.

10. Has a known history of or is positive for hepatitis B (hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (hepatitis C virus [HCV] RNA [qualitative] is detected). No testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority. Refer to Appendix 7 for Germany-specific requirements.

11. Has a known history of immunosuppression or is receiving systemic steroid therapy or any other form of systemic immunosuppressive therapy within 7 days prior to the first dose of study intervention.

12. Grade 2 or higher nonhematological toxicities from prior therapy. Residual toxicity of Grade 1 from prior therapy or persistent treatment-related Grade 1 neurotoxicity will be allowed.

 

Prior/Concomitant Therapy

13. Has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years. (Participants who have had a transplant greater than 5 years ago are eligible as long as there are no symptoms of Graft versus Host Disease.)

14. Has received prior therapy with an anti-LAG-3 antibody.

15. Has received CAR-T cells therapy.

16. Cohort 1 only: Has received prior therapy with an anti-PD-1 or anti-PD-L1 antibody.

17. Treatment with anticancer therapy or thoracic radiation therapy within 14 days before the first dose of study intervention.

18. Has had a prior anticancer monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (ie, ≤ Grade 1 or at baseline) from AEs due to agents administered more than 4 weeks earlier.

19. Has received a live vaccine within 30 days prior to first dose.

 

Prior/Concurrent Clinical Study Experience

20. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 28 days before study Day 1.

 

Trial design

  • Phase I
  • Multicenter
  • Prospective
  • Cohort
  • Open Label

Intervention

  • Pembrolizumab 200mg every 3 weeks until progress (or up to max. of 35 cycles / 24 months)
  • MK 42-80 200mg (starting dose); 100mg -700mg (may be explored based on mTPI and efficacy results during Safety Lead-In. Intermediate doses may be explored as necessary.

Documents (password protected)

Responsibilities in overall trial

Merck Sharp & Dohme Corp.

  • Tel. +1 (908) 740-4000

National Coordinating Investigator

Priv.-Doz. Dr. med. Bastian von Tresckow

Study Sites

Klinik I für Innere Medizin

Study office

  • Klinisches Studienzentrum der Klinik I für Innere Medizin Köln

Status

Active

Principal Investigator

Priv.-Doz. Dr. med. Bastian von Tresckow

Deputy of Principal Investigator

  • Prof. Dr. med. Peter Borchmann
  • Dr. med. Armin Tuchscherer

Subinvestigator

  • Dr. med. Paul Bröckelmann
  • Dr. med. Sarah Gillessen
  • Jesko Momotow
  • Dr. med. Janine Böll, geb. Schwamb
  • Dr. med. Birgit Cremer
  • Dr. med. Anja Jühling
  • Dr. Stefanie Kreissl
  • Prof. Dr. med. Christian Pallasch
  • Johanna Prinz
  • PD Dr. med. Stephanie Sasse
  • Univ.-Prof. Dr. med. Dr. rer.-nat. Roland Ullrich
  • PD Dr. med. Thomas Zander

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