A Study to Determine Dose and Regimen of Durvalumab as Monotherapy or in Combination With Pomalidomide With or Without Dexamethasone in Subjects With Relapsed and Refractory Multiple Myeloma

A Phase IB Multicenter, Open-label Study To Determine The Recommended Dose And Regimen Of Durvalumab (MEDI4736) Either As Monotherapy or In Combination With Pomalidomide (POM) With Or Without Low-Dose Dexamethasone (DEX) In Subjects With Relapsed And Refractory Multiple Myeloma (RRMM)

This is a multicenter, open-label, Phase 1b study to determine the recommended dose and regimen of durvalumab either as monotherapy or in combination with POM with or without low dose dex in subjects with RRMM. The study will consist of a dose-finding portion as well as a parallel dose-expansion portion to determine the optimal dose and regimen.

On 05 Sep 2017, a Partial Clinical Hold was placed on this study by the United States (US) Food and Drug Administration (FDA). The decision by the FDA was based on data related to risks of anti-programmed cell death-1 (PD-1) antibody, pembrolizumab, in combination with IMiDs® immunomodulatory drugs in patients with multiple myeloma. As a result, enrollment into this study has been discontinued. Subjects who are receiving clinical benefit, based on the discretion of the investigator, may remain on study treatment after being reconsented.

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Dexamethasone; Drug: Durvalumab; Drug: Pomalidomide

• Study Type: Interventional
• Enrollment (Actual): 114
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Local Institution - 201
• France
  • Lille, France, 59037
    • Local Institution - 601
  • Poitiers Cedex, France, 86021
    • Local Institution - 602
  • Toulouse CEDEX 9, France, 31059
    • Local Institution - 603
• Germany
  • Tuebingen, Germany, 72076
    • Local Institution - 301
• Italy
  • Pavia 2, Italy, 27100
    • Local Institution - 403
  • Rozzano (MI), Italy, 20089
    • Local Institution - 405
  • Torino, Italy, 10126
    • Local Institution - 401
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Local Institution - 702
  • Rotterdam, Netherlands, 3015 CN
    • Local Institution - 701
• Spain
  • Barcelona, Spain, 08916
    • Local Institution - 501
  • Madrid, Spain, 28041
    • Local Institution - 504
  • Pamplona, Spain, 31008
    • Local Institution - 502
  • Valencia, Spain, 46026
    • Local Institution - 505
• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Local Institution - 102
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Local Institution - 114
    • Boston, Massachusetts, United States, 02115
      • Local Institution - 108
    • Boston, Massachusetts, United States, 02215
      • Local Institution - 115
  • New York
    • New York, New York, United States, 10065
      • Local Institution - 105
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Local Institution - 106
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Local Institution - 110
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Local Institution - 107

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Has a confirmed diagnosis of active multiple myeloma and measurable disease.
• Must have undergone prior treatment with ≥2 treatment lines of anti-myeloma therapy
• Must have failed last line of treatment (refractory to last line of treatment).
• Must have achieved at least a stable disease (SD) for at least 1 cycle of treatment to at least 1 prior anti-myeloma regimen before developing Progressive disease (PD) (relapsed)
• Prior anti-myeloma treatments must have included a lenalidomide AND proteasome inhibitor alone or in combination.
• Has performance status of 0, 1, or 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• The extramedullary plasmacytoma (EMP) sub-group, must have radiologically measurable EMP disease (soft tissue or bone related) that is amenable to biopsy and does not need to have measurable disease.

Exclusion Criteria:

• Has non-secretory or oligosecretory multiple myeloma
• Has had prior anti-myeloma therapy within 2 weeks prior to study Day 1
• Has undergone prior organ or allogeneic hematopoetic stem cell transplantation
• Has received previous therapy with pomalidomide and did not achieve at least a stable disease
• Has received prior therapy with an anti-programmed cell death 1 receptor (anti-PD-1), antiprogrammed death-ligand 1 (anti-PD-L1), antiprogrammed death-ligand 2 (anti-PD-L2), anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways).
• Has received prior treatment with a monoclonal antibody within 5 half-lives of Study Day 1
• Has received investigational agents within 28 days or 5 half-lives (whichever is longer) of Study Day 1
• Has received live, attenuated vaccine within 30 days prior to Study Day 1
• Had rash ≥ Grade 3 during prior thalidomide, lenalidomide, or pomalidomide therapy
• Has a history of anaphylaxis or hypersensitivity to thalidomide, lenalidomide, POM, or dex
• Has peripheral neuropathy ≥ Grade 2
• Has a known additional malignancy that is progressing or requires active treatment (except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy).
• Is positive for human immunodeficiency virus (HIV), chronic or active hepatitis B or active hepatitis A or C
• Has a prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years (with the exception Basal cell carcinoma of the skin, Squamous cell carcinoma of the skin, Carcinoma in situ of the cervix, Carcinoma in situ of the breast, Incidental histologic finding of prostate cancer [T1a or T1b] or prostate cancer that is curative)
• Has clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS multiple myeloma
• Has clinically significant cardiac disease
• Is a female who is pregnant, nursing, or breastfeeding, or who intends to become pregnant during the participation in the study
• Is a current smoker

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Durvalumab monotherapy; Intravenous (IV) durvalumab at assigned dose level (750, 1500, 2250, or 3000 mg) over 1 hour on day 1 of a 28-day cycle	Drug: Durvalumab; Other Names: MEDI4736
Experimental: Durvalumab + pomalidomide (POM); IV durvalumab at assigned dose level (750, 1500, 2250, or 3000 mg) over 1 hour on day 1 of a 28-day cycle and Oral POM 4 mg/day on Days 1 to 21 of each 28-day treatment cycle	Drug: Durvalumab; Other Names: MEDI4736; Drug: Pomalidomide
Experimental: Durvalumab + pomalidomide (POM) + dexamethasone (dex); IV durvalumab at assigned dose level (750, 1500, 2250, or 3000 mg) over 1 hour on day 1 of a 28-day cycle with Oral POM 4 mg/day on Days 1 to 21 of each 28-day treatment cycle and Oral dex 40 mg/day (≤ 75 years old) or 20 mg/day (> 75 years old) on Days 1, 8, 15, and 22 of a 28-day cycle	Drug: Dexamethasone; Drug: Durvalumab; Other Names: MEDI4736; Drug: Pomalidomide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting Toxicities (DLTs)	Number of participants with DLTs in the first cycle of treatment	Approximately 1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AEs)	Number of participants with adverse events	Up to approximately 2 year
Overall response rate (ORR)	Tumor response, including progressive disease (PD) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria	Up to approximately 2 year
Time to response (TTR)	Time from first dose to the first documentation of response (Partial Response [PR] or greater)	Up to approximately 2 year
Duration of response (DOR)	Is defined as time from the earliest date of documented response (partial response (PR) or better) to the earliest date when disease progression was confirmed	Up to approximately 2 year
Pharmacokinetics- Cmax	Maximum observed concentration	Up to approximately 1 year
Pharmacokinetics- AUC	Area under the concentration-time curve	Up to approximately 1 year
Pharmacokinetics- Tmax	Time to maximum concentration	Up to approximately 1 year
Pharmacokinetics- t1/2	Terminal elimination half-life	Up to approximately 1 year
Pharmacokinetics- CL/F	Apparent total body clearance	Up to approximately 1 year
Pharmacokinetics- Vz/F	Volume of distribution	Up to approximately 1 year

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Lars Sternas, MD, PhD, Celgene Corporation

Publications and helpful links

General Publications

• Young MH, Pietz G, Whalen E, Copeland W, Thompson E, Fox BA, Newhall KJ. Immunomodulation by durvalumab and pomalidomide in patients with relapsed/refractory multiple myeloma. Sci Rep. 2021 Aug 12;11(1):16460. doi: 10.1038/s41598-021-95902-x.

Helpful Links

• BMS Clinical Trial Information
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2016
• Primary Completion (Actual): November 23, 2018
• Study Completion (Estimated): July 30, 2024

Study Registration Dates

• First Submitted: November 25, 2015
• First Submitted That Met QC Criteria: November 25, 2015
• First Posted (Estimated): November 30, 2015

Study Record Updates

• Last Update Posted (Actual): August 7, 2024
• Last Update Submitted That Met QC Criteria: August 5, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Multiple Myeloma; Relapsed; Refractory; PD-L1; Durvalumab; MEDI4736; Dexamethasone (DEX); Pomalidomide (POM)
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dexamethasone; Pomalidomide; Durvalumab
• Other Study ID Numbers: MEDI4736-MM-001