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Phase 2 Completed N=18 Treatment

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)

Source: ClinicalTrials.gov NCT03000452 ↗
Enrolled (actual)
18
Serious AEs
38.9%
Results posted
Oct 2018
Primary outcomePrimary: Percentage of Participants With an Objective Response According to International Myeloma Working Group (IMWG) Uniform Response Criteria — 0.0 percentage of participants

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.

Outcome Measures

OutcomeResultp-value
PRIMARY
Percentage of Participants With an Objective Response According to International Myeloma Working Group (IMWG) Uniform Response Criteria
0.0
SECONDARY
Time-to-Response (TTR)
SECONDARY
Duration of Response (DOR)
SECONDARY
Progression Free Survival
SECONDARY
Overall Survival
SECONDARY
Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration Of Durvalumab
3145469.40
SECONDARY
Area Under the Plasma Concentration-time Curve From Time 0 to Extrapolated to Infinity (AUC-inf) of Durvalumab
5634957.81
SECONDARY
Maximum Observed Concentration (Cmax) Of Durvalumab
349391.46
SECONDARY
Time to Reach Maximum Concentration (Tmax) of Durvalumab
0.0476
SECONDARY
Terminal Half-Life (T1/2) of of Durvalumab
15.71
SECONDARY
Apparent Total Clearance (CL/F) of of Durvalumab
0.27
SECONDARY
Apparent Volume of Distribution (Vz/F) of Durvalumab
5.48
SECONDARY
Participants With Treatment-Emergent Adverse Events (TEAEs)
18; 1; 4; 4; 11; 1

Eligibility Criteria

Inclusion Criteria

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.
  • Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
  • Females of childbearing potential (FCBP) must:

a. Have 2 negative pregnancy tests as verified by the investigator prior to starting study treatment. This applies even if the subject practices true abstinence from heterosexual contact.

i. Negative serum pregnancy test at screening ii. Negative serum or urine pregnancy test (investigator's discretion) within 72 hours prior to starting study treatment (Cycle 1, Day 1), and before beginning each subsequent cycle of treatment, and after end of study treatment.

b. Either practice true abstinence from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with, effective contraception without interruption (eg, oral, inject able, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; true abstinence; or vasectomized partner), 28 days prior to starting study treatment, during the study therapy (including dose interruptions), and for at least 90 days after discontinuation of study treatment.

c. Agree to abstain from breastfeeding during study participation and for at least 90 days after the last dose of Daratumumab (DARA) or Durvalumab (DURVA), whichever is later.

d. Refrain from egg cell donation for at least 90 days after the final dose of DURVA or DARA, whichever is later.

  • Male subjects must:
  • Either practice true abstinence (which must be reviewed on a monthly basis) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 90 days following study treatment discontinuation, even if he has undergone a successful vasectomy.
  • Refrain from sp
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03000452). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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