Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Dexamethasone

Durvalumab

Daratumumab

Pomalidomide

Dexamethasone acetate

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Antineoplastic Agents, Immunological

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

* Intravenous (IV) durvalumab at 1500mg on Day 1 or 2 of a 28-day cycle
* IV daratumumab at 16mg/kg on days 1, 8, 15 and 22 at cycles 1-2; on days 1 and 15 at cycles 3-6; and on day 1 from cycle 7 onward

* Intravenous (IV) durvalumab at 1500mg on Day 1 or 2 of a 28-day cycle
* IV daratumumab at 16mg/kg on days 1, 8, 15 and 22 at cycles 1-2; on days 1 and 15 at cycles 3-6; and on day 1 from cycle 7 onward
* oral POM at 4mg/day on days 1 to 21
* oral/IV dex at 40mg/day (\>75 years old) or 20mg/day (\>75 years old) on days 1, 8, 15 and 22

Bristol-Myers Squibb

This is an open-label, multicenter study to confirm the safety and efficacy of durvalumab + daratumumab (D2) in subjects with relapsed and refractory multiple myeloma. This study will also explore the safety and efficacy of the addition of pomalidomide + dexamethasone to durvalumab + daratumumab (PD3).

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.

A Study to Determine the Safety and Efficacy for the Combination of Durvalumab and Daratumumab in Relapsed and Refractory Multiple Myeloma

A Phase 2, Multicenter, Open-label, Study to Determine the Safety and Efficacy for the Combination of Durvalumab (DURVA) and Daratumumab (DARA) (D2) in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM)

Tumor response of partial response (PR) or better was assessed using the International Myeloma Working Group (IMWG) Uniform Response Criteria. ORR was calculated as the percent of responders (multiplied by 100). Partial response required ≥ 50% reduction of serum M-Protein and reduction in 24-hour urinary M protein by ≥ 90% or to \< 200 mg per 24 hours.

Number of participants who experienced at least one adverse event. An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening (i.e., any clinically significant adverse change in the frequency or intensity of a preexisting condition should be considered an AE.

Number of participants who experienced at least one serious adverse event. An SAE is any AE occurring at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, constitutes an important medical event.

Time-to-response is calculated as the time from enrollment to the first date of documented response (partial response or better). Tumor response of partial response (PR) or better was assessed using the International Myeloma Working Group (IMWG) Uniform Response Criteria. Partial response required ≥ 50% reduction of serum M-Protein and reduction in 24-hour urinary M protein by ≥ 90% or to \< 200 mg per 24 hours. For those participants where POM + DEX were added, time-to-response was calculated from the date POM and DEX were added to the first date of documented response (PR or better).

Duration of response was calculated as the time from the earliest date of documented response (PR or better) to the earliest date of disease progression as determined by the investigator. For those participants where POM + DEX was added, duration of response was calculated as the time from the earliest date of documented response after POM + DEX was added (PR or better) to the earliest date of disease. Tumor response of partial response (PR) or better was assessed using the International Myeloma Working Group (IMWG) Uniform Response Criteria. Partial response required ≥ 50% reduction of serum M-Protein and reduction in 24-hour urinary M protein by ≥ 90% or to \< 200 mg per 24 hours. Progressive Disease required increase of 25% from lowest response value in the serum M-component (absolute increase must be ≥ 0.5 g/dL) and/or urine M-component (absolute increase must be ≥ 200 mg/24 h).

Duration of response was calculated as the time from the earliest date of documented response (PR or better) to the earliest date of disease progression as determined by the investigator. For those participants where POM + DEX was added, duration of response was calculated as the time from the earliest date of documented response after POM + DEX was added (PR or better) to the earliest date of disease progression as determined by the investigator. Participants who are alive or lost to follow-up will be censored on the last-known-to-be-alive date. Tumor response of partial response (PR) or better was assessed using the International Myeloma Working Group (IMWG) Uniform Response Criteria. Partial response required ≥ 50% reduction of serum M-Protein and reduction in 24-hour urinary M protein by ≥ 90% or to \< 200 mg per 24 hours.

Progression-free survival was calculated as the time between the enrollment to the first documentation of progressive disease or death from any cause during study, whichever occurs earlier using the International Myeloma Working Group (IMWG) Uniform Response Criteria. Progressive Disease required increase of 25% from lowest response value in the serum M-component (absolute increase must be ≥ 0.5 g/dL) and/or urine M-component (absolute increase must be ≥ 200 mg/24 h).

Pharmacokinetics of Durvalumab derived from serum concentration versus time data.

Celgene

Durvalumab 1500 mg + Daratumumab 16 mg/kg were administered intravenously within a 28-day cycle for a maximum of 60 cycles. POM + DEX could be added to the D2 regimen, at the investigator's discretion, upon confirmed progressive disease for participants who had at least 2 cycles of D2.

Simon Stage 1: D2 Arm

Durvalumab 1500 mg IV + Daratumumab 16 mg/kg IV + Pomalidomide 4 mg/day Oral + Dexamethasone 40 mg Oral (20 mg for \> 75 Years Old) administered within a 28-day cycle for a maximum of 22 cycles

PD3 Arm

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

White

Other

Race/Ethnicity, Customized

This study stopped enrolling participants on 05-Sep-2017 and was terminated earlier than planned on 03-Jan-2022. This results disclosure report provides outputs from the Simon Stage 1: D2 and PD3 arms. Simon Stage 2: D2 did not enroll any participants.

Bristol-Myers Squibb Study Director

All enrolled participants who received at least 1 dose of the study medication, and who have measurable disease at baseline and at least 1 postbaseline efficacy assessment.

Overall Response Rate (ORR)

All participants who received at least 1 dose of the study medications.

Number of Participants With Adverse Events (AEs)

Number of Participants With Serious Adverse Events (SAEs)

Durvalumab 1500 mg + Daratumumab 16 mg/kg were administered intravenously within a 28-day cycle for a maximum of 60 cycles

Durvalumab 1500 mg IV + Daratumumab IV 16 mg/kg + Pomalidomide 4 mg/day Oral + Dexamethasone 40 mg Oral (20 mg for \> 75 Years Old) were administered within a 28-day cycle for a maximum of 60 cycles

Simon Stage 1: D2 + Pomalidomide + Dexamethasone

All enrolled participants who received at least 1 dose of the study medication, and who have measurable disease at baseline and at least 1 postbaseline efficacy assessment in the D2, D2 + Pomalidomide + Dexamethasone, and PD3 arms.

Time-To-Response (TTR)

Durvalumab 1500 mg IV + Daratumumab 16 mg/kg IV + Pomalidomide 4 mg/day Oral + Dexamethasone 40 mg Oral (20 mg for \> 75 Years Old) were administered within a 28-day cycle for a maximum of 60 cycles

All enrolled participants with a partial response or better, who received at least 1 dose of the study medication, and who have measurable disease at baseline and at least 1 postbaseline efficacy assessment. Pre-specified for data to be collected only in D2 and D2 + Pomalidomide + Dexamethasone arms.

Kaplan-Meier Estimate of Duration of Response (DOR) - Simon Stage 1: D2 Arm

All enrolled participants with a partial response or better, who received at least 1 dose of the study medication, and who have measurable disease at baseline and at least 1 postbaseline efficacy assessment. Pre-specified for data to be collected only in the PD3 arm.

Kaplan-Meier Estimate of Duration of Response (DOR) - PD3 Arm

All participants who received at least 1 dose of the study medications. Pre-specified for data to be collected only in D2 and D2 + Pomalidomide + Dexamethasone arms.

Kaplan-Meier Estimate of Progression-Free Survival (PFS) - Simon Stage 1: D2 Arm

All participants who received at least 1 dose of the study medications. Pre-specified for data to be collected only in the PD3 arm.

Kaplan-Meier Estimate of Progression-Free Survival (PFS) - PD3 Arm

Durvalumab 1500 mg + Daratumumab 16 mg/kg were administered intravenously within a 28-day cycle for a maximum of 60 cycles.

All participants who received at least 1 dose of study medication and who have at least 1 measurable plasma concentration. Cmax was a pre-specified secondary outcome measure in the Simon Stage 1: D2 arm only.

Maximum Observed Plasma Concentration (Cmax) - Simon Stage 1: D2 Arm

All participants who received at least 1 dose of study medication and who have at least 1 measurable plasma concentration. Tmax was a pre-specified secondary outcome measure in the Simon Stage 1: D2 arm only.

Time of Maximum Observed Concentration (Tmax) - Simon Stage 1: D2 Arm

All participants who received at least 1 dose of study medication and who have at least 1 measurable plasma concentration. \[AUC(0-Last)\] was a pre-specified secondary outcome measure in the Simon Stage 1: D2 arm only.

Area Under the Plasma Concentration-Time Curve to the Last Measurable Plasma Concentration [AUC(0-Last)] - Simon Stage 1: D2 Arm

All participants who received at least 1 dose of study medication and who have at least 1 measurable plasma concentration. \[AUC(TAU)\] was a pre-specified secondary outcome measure in the Simon Stage 1: D2 arm only.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study to Determine the Safety and Efficacy for the Combination of Durvalumab and Daratumumab in Relapsed and Refractory Multiple Myeloma	NCT02807454	Multiple Myelom...	Daratumumab Durvalumab Pomalidomide Dexamethasone	18 Years -	Celgene
A Study to Determine the Safety and Efficacy for the Combination of Durvalumab and Daratumumab in Relapsed and Refractory Multiple Myeloma	NCT02807454	Multiple Myelom...	Daratumumab Durvalumab Pomalidomide Dexamethasone	18 Years -	Celgene

Spots Global Cancer Trial Database for relapsed and refractory (rrmm)