NCT03715478

Brief Summary

This is a Phase 1/2, multi-centre, single-arm, open-label, dose-escalation study that will evaluate the safety and efficacy of IV GSK2857916 in combination with PO pomalidomide and low-dose PO dexamethasone in subjects with relapsed and/or refractory MM.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
120

participants targeted

Target at P75+ for phase_1

Timeline
8mo left

Started Nov 2018

Longer than P75 for phase_1

Geographic Reach
1 country

9 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress92%
Nov 2018Dec 2026

First Submitted

Initial submission to the registry

October 2, 2018

Completed
21 days until next milestone

First Posted

Study publicly available on registry

October 23, 2018

Completed
1 month until next milestone

Study Start

First participant enrolled

November 26, 2018

Completed
6.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2025

Completed
1.6 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2026

Expected
Last Updated

January 8, 2025

Status Verified

January 1, 2025

Enrollment Period

6.5 years

First QC Date

October 2, 2018

Last Update Submit

January 7, 2025

Conditions

Relapsed and/or Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

  • Recommended Phase 2 Dose (RP2D)

    RP2D and schedule of GSK2857916 for Part 2 will be determined by Part 1 of the study

    9 months

  • Overall Response Rate (ORR)

    Overall response rate will be the percentage of patients achieving partial response or better according to IMWG response criteria

    60 months

Secondary Outcomes (3)

  • Treatment Emergent Adverse Events

    60 months

  • Progression Free Survival

    60 months

  • Maximum tolerated dose (MTD)

    9 months

Study Arms (1)

GSK2857916 with Pomalidomide and Dexamethasone

EXPERIMENTAL

This will be a single arm study of GSK2857916 administered with pomalidomide and dexamethasone. GSK2857916 will be administered intravenously either on Day 1 of each 28 day cycle (Single Dose) or on Days 1 and 8 (Split Dose) and up to 4 dose levels will be evaluated during the phase I portion. Pomalidomide will be administered orally on Days 1-21 at 4 mg. Dexamethasone will be administered orally at 40 mg for patients ≤ 75 years old or 20 mg for patients older than 75 on days 1, 8, 15, 22.

Drug: GSK2857916 with Pomalidomide and Dexamethasone

Interventions

GSK2857916 with Pomalidomide and DexamethasoneDRUG

Recommended phase 2 dose (RP2D) of GSK2857916 determined by the phase 1 portion of study will be administered in combination with pomalidomide (approved dose and schedule) and dexamethasone until progression of disease.

Also known as: Pomalyst
GSK2857916 with Pomalidomide and Dexamethasone

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Must be able to understand and voluntarily sign an informed consent form (ICF).
  • Must be ≥ 18 years of age at the time of signing the ICF.
  • Must be able to adhere to the study visit schedule and other protocol requirements.
  • Documented diagnosis of MM and relapsed and/or refractory disease with:
  • Have undergone stem cell transplant, or have been considered transplant ineligible
  • Previously treated with two or more prior lines of treatment that must have included lenalidomide and a proteasome inhibitor (in separate regimens or in combination). Induction therapy followed by ASCT and consolidation/maintenance will be considered as one line.
  • Documented evidence of progressive disease (PD) after achieving at least stable disease (SD) for ≥ 1 cycle during a previous MM treatment (i.e., relapsed MM) and/or
  • Disease progression during or within 60 days from the end of the most recent MM treatment (i.e., refractory MM).
  • Subjects with a history of autologous stem cell transplant are eligible for study participation provided the following eligibility criteria are met:
  • transplant was \> 100 days prior to study enrolment
  • no active infection
  • Subjects with measurable disease defined as at least one of the following (these baseline laboratory studies for determining eligibility must be obtained within 28 days prior to start of study drug):
  • Serum M-protein ≥ 5 g/l
  • Urine M-protein ≥ 200 mg/24 h
  • Serum free light chains (FLC) assay: Involved FLC level ≥ 100 mg/l and an abnormal serum free light chain ratio (\< 0.26 or \> 1.65)
  • +16 more criteria

You may not qualify if:

  • Prior pomalidomide or BCMA therapy use.
  • History of allegeneic transplant
  • Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions (including lab abnormalities) that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures.
  • Pregnant or lactating females.
  • Subjects with previous or concurrent malignancies are allowed only if the second tumor is not contributing to the subject's illness. The subject must not be receiving active therapy, other than hormonal therapy for this disease and the disease must be considered medically stable for at least 2 years.
  • Evidence of cardiovascular risk including any of the following:
  • QTc interval ≥ 470 msecs. NOTE: The QT interval should be corrected for the heart rate by Fridericia's formula (QTcF)
  • Evidence of current clinically significant uncontrolled arrhythmias; including clinically significant ECG abnormalities; including 2nd degree (Type II) or 3rd degree atrioventricular (AV) block.
  • History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within six months of Screening.
  • Class III or IV heart failure as defined by the New York Heart Association functional classification system (Appendix 3)
  • Uncontrolled hypertension
  • Presence of hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (HBcAb at screening or within 3 months prior to first dose of study treatment. Participants with positive hepatitis B core antibody (HBcAb) can be enrolled, only if confirmatory negative Hepatitis B DNA is obtained AND patient is on hepatitis B prophylaxis (tenofovir or entecavir) before first dose of study drug.
  • Positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study treatment. Note: Participants with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained. Note: Hepatitis RNA testing is optional and participants with negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing.
  • Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Note: Stable chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if participant otherwise meets entry criteria.
  • Current corneal epithelial disease except for mild punctate keratopathy (mild punctate keratopathy is allowed).
  • +9 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

Cross Cancer Institute

Edmonton, Alberta, Canada

Location

Vancouver General Hospital

Vancouver, British Columbia, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Location

QEII Health Sciences Centre

Halifax, Nova Scotia, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, Canada

Location

London Health Sciences Centre

London, Ontario, Canada

Location

The Ottawa Hospital

Ottawa, Ontario, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada

Location

Related Publications (1)

  • Trudel S, McCurdy A, Louzada ML, Parkin S, White D, Chu MP, Kotb R, Mian H, Othman I, Su J, Khan A, Gul E, Reece D. Belantamab mafodotin, pomalidomide and dexamethasone in refractory multiple myeloma: a phase 1/2 trial. Nat Med. 2024 Feb;30(2):543-551. doi: 10.1038/s41591-023-02703-y. Epub 2024 Jan 4.

    PMID: 38177852DERIVED

MeSH Terms

Interventions

belantamab mafodotinpomalidomideDexamethasone

Intervention Hierarchy (Ancestors)

PregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsSteroids, Fluorinated

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 2, 2018

First Posted

October 23, 2018

Study Start

November 26, 2018

Primary Completion

June 1, 2025

Study Completion (Estimated)

December 31, 2026

Last Updated

January 8, 2025

Record last verified: 2025-01

Data Sharing

IPD Sharing
Will not share

Locations

CA(9)