A Study to Determine the Efficacy of the Combination of Daratumumab (DARA) Plus Durvalumab (DURVA) (D2) in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM)

NCT03000452 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: MEDI4736-MM-005
• Study Type: interventional
• Target: 18
• Locations: 6 countries
• Sites: 25

Brief Summary

This is a single-arm, multicenter, Phase 2 study to evaluate the efficacy and safety of the combination regimen of daratumumab plus durvalumab (D2). The study will consist of 2 parts; Part 1 has a 2-stage design while Part 2 consists of an expansion phase. Subjects will receive intravenous (IV) DARA at 16 mg/kg on the same dosing schedule (weekly \[QW\], every 2 weeks \[Q2W\] or every 4 weeks \[Q4W\] of each 28-day cycle) received on their last prior therapy containing DARA. The dosing schedule for DARA may be adjusted during the course of the study as outlined in the protocol. Subjects will also receive IV DURVA at 1500 mg on Day 2 (Cycle 1) and on Day 1 (Cycles ≥ 2) of each 28-day treatment cycle.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Daratumumab; Durvalumab; Relapsed and Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With an Objective Response According to International Myeloma Working Group (IMWG) Uniform Response Criteria

  Objective response is defined as a best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR) based on the investigator assessment: sCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level \< 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to \< 200 mg/24 hours. In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required.

  From randomization until the data cut-off date of 17 April 2018. The median duration of treatment for durvalumab and daratumumab was 7.9 weeks and 8.0 weeks respectively.

Secondary Outcomes (12)

• Time-to-Response (TTR)

  From randomization until the data cut-off date of 17 April 2018. The median duration of treatment for durvalumab and daratumumab was 7.9 weeks and 8.0 weeks respectively.

• Duration of Response (DOR)

  From randomization until the data cut-off date of 17 April 2018. The median duration of treatment for durvalumab and daratumumab was 7.9 weeks and 8.0 weeks respectively.

• Progression Free Survival

  From randomization until the data cut-off date of 17 April 2018. The median duration of treatment for durvalumab and daratumumab was 7.9 weeks and 8.0 weeks respectively.

• Overall Survival

  From randomization until the data cut-off date of 17 April 2018. The median duration of treatment for durvalumab and daratumumab was 7.9 weeks and 8.0 weeks respectively.

• Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration Of Durvalumab

  Pharmacokinetic samples were drawn on Cycle 1 on Day 2 (C1D2) pre-dose, at the end of the infusion, on Day 8 at 144 hour post dose, on Day 15 at 312 hours post dose and on Day 22 at 480 hours post C1D2 infusion.

Study Arms (1)

Administration of Daratumumab (DARA) plus Durvalumab (DURVA)

EXPERIMENTAL

Subjects will also receive IV DURVA at 1500 mg on Day 2 (Cycle 1) and on Day 1 (Cycles ≥ 2) of each 28-day treatment cycle. Subjects will receive intravenous (IV) DARA at 16 mg/kg on the same dosing schedule (weekly \[QW\], every 2 weeks \[Q2W\], or every 4 weeks \[Q4W\] of each 28-day treatment cycle) received during their last prior therapy containing DARA at the time of DARA progression

Drug: DARATUMUMAB; Drug: DURVALUMAB

Interventions

DARATUMUMAB DRUG

DARATUMUMAB

Also known as: DARA

Administration of Daratumumab (DARA) plus Durvalumab (DURVA)

DURVALUMAB DRUG

DURVALUMAB

Also known as: MEDI4736; DURVA

Administration of Daratumumab (DARA) plus Durvalumab (DURVA)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must satisfy the following criteria to be enrolled in the study:
• Subject received at least 3 prior anti-myeloma regimens including a proteasome inhibitor (PI) and an immunomodulatory agent or is double-refractory to a PI and an immunomodulatory agent.
• Induction, bone marrow transplant with or without maintenance therapy is considered one regimen.
• Refractory is defined as disease that is nonresponsive on therapy, or progresses within 60 days of last therapy. Nonresponsive disease is defined as either failure to achieve minimal response or development of progressive disease while on therapy.
• For subjects who received more than 1 regimen containing a PI their disease must be refractory to the most recent PI containing regimen.
• For subjects who received more than 1 regimen containing a immunomodulatory agent their disease must be refractory to the most recent immunomodulatory agent containing regimen.
• All subjects must have failed Daratumumab (DARA) either as a single agent or in combination on last Multiple myeloma (MM) therapy. Failure is defined as disease progression(PD) on DARA either as a single agent or in combination.
• Subject has measurable disease defined as:
• M-protein (serum protein electrophoresis (sPEP) or urine protein electrophoresis (uPEP): sPEP ≥ 0.5 g/dL or uPEP ≥ 200 mg/24 hours) and/or
• Light chain MM without measurable disease in the serum or the urine: serum immunoglobulin free light chain ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio
• Subject achieved a response (minimal response \[MR\] or better) to at least 1 prior treatment regimen.
• Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 2 or less.
• Subject's toxicities resulting from previous therapy (including peripheral neuropathy) have resolved or stabilized to ≤ Grade 1.
• Subject is at least 18 years of age the time of signing the informed consent form (ICF).
• Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.

You may not qualify if:

• The presence of any of the following will exclude a subject from enrollment:
• Subject has had prior exposure to anti-CTLA-4, anti-PD-1 (Programmed cell death-1), anti-PD-L1 (Programmed death-ligand 1) Monoclonal antibody (mAbs), or cancer vaccines
• Subject has received autologous stem cell transplantation (ASCT) within 12 weeks before the date of randomization.
• History of organ or allogeneic stem cell transplantation
• Subject received any of the following within the last 14 days of initiating study treatment:
• Plasmapheresis
• Major surgery (as defined by the investigator)
• Radiation therapy other than local therapy for myeloma associated bone lesions
• Use of any systemic anti-myeloma drug therapy (except for DARA either alone or in combination with other agents given with it)
• Subject received prior treatment with a monoclonal antibody within 5 half-lives of initiating study treatment, other than DARA.
• Subject is receiving concurrent chemotherapy or biologic or hormonal therapy for cancer treatment. Note: Concurrent use of hormones for noncancer-related conditions (eg, insulin for diabetes and hormone replacement therapy) is acceptable.
• Subject has any of the following laboratory abnormalities:
• Absolute neutrophil count (ANC) \< 1,000/µL
• Platelet count: \< 75,000/µL (it is not permissible to transfuse a subject to reach this level)
• Hemoglobin \< 8 g/dL (\< 4.9 mmol/L) (it is not permissible to transfuse a subject to reach this level)

Sponsors & Collaborators

• Celgene: lead

Study Sites (25)

City of Hope Cancer Center

Duarte, California, 91010-300, United States

Location

Cancer Center of Central Connecticut

Southington, Connecticut, 06489, United States

Location

Parkview Research Center

Fort Wayne, Indiana, 46845, United States

Location

Indiana University Cancer Center

Indianapolis, Indiana, 46202-528, United States

Location

University of Kansas Hospital

Westwood, Kansas, 66205, United States

Location

University of Maryland School of Med

Baltimore, Maryland, 21201-1595, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Morristown Memorial Hosp

Morristown, New Jersey, 07962, United States

Location

OHSU

Portland, Oregon, 97201, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Universitaetsklinik Innsbruck

Innsbruck, 6020, Austria

Location

Salzburger Landkliniken St. Johanns-Spital

Salzburg, 5020, Austria

Location

Medizinische Universitat Wien

Vienna, 1090, Austria

Location

Alexandra General Hospital of Athens

Athens, 11528, Greece

Location

UMCU Utrecht

Utrecht, 3584 CX, Netherlands

Location

Hospital Universitari Germans Trias i Pujol Can Ruti

Badalona (Barcelona), 08916, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Dr. Pesset

Valencia, 46017, Spain

Location

Falu lasarett

Falun SE, 79182, Sweden

Location

Helsingborg hospital

Helsingborg, 254 37, Sweden

Location

Lund University Hosptial

Lund, 22185, Sweden

Location

Karolinska University Hospital Huddinge

Stockholm, 14186, Sweden

Location

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

daratumumab; durvalumab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

An independent DMC reviewed data from Part 1 Stage 1 of the study on 26 Oct 2017; based on their recommendations, Celgene decided to close the study due to unfavorable efficacy results (number of responses to move to Stage 2 was not reached).

Results Point of Contact

• Title: Anne McClain, Senior Manager, Clinical Trial Disclosure
• Organization: Celgene Corporation

ClinicalTrialDisclosure@Celgene.com

888-260-1599

Study Officials

• Steven Novick, MD, PhD

  Celgene Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2016
• First Posted: December 22, 2016
• Study Start: March 14, 2017
• Primary Completion: September 18, 2017
• Study Completion: December 4, 2017
• Last Updated: October 16, 2018
• Results First Posted: October 16, 2018

Record last verified: 2018-09

Locations

GR (1); US (12); NL (1); AU (3); ES (4); SE (4)