Open-label, randomized study of two doses of GSK2857916 in participants with relapsed/refractory multiple myeloma who have failed prior treatment with an anti-CD38 antibody

Phase 1

• Conditions: Relapsed/Refractory Multiple Myeloma; MedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-004810-25-IT
• Lead Sponsor: GLAXOSMITHKLINE RESEARCH AND DEVELOPMENT

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-17
• Last Update Posted: 7 September 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 221

Inclusion Criteria

Participants are eligible to be included in the study only if all of the following criteria
apply:
1. Provide signed written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
2. Male or female, 18 years or older (at the time consent is obtained)
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (Appendix 8 of the protocol)
4. Histologically or cytologically confirmed diagnosis of MM as defined according to IMWG, [Rajkumar, 2014] criteria, and a) Has undergone stem cell transplant or is considered transplant ineligible, and b) Has failed at least 3 prior lines of anti-myeloma treatments, including an anti- CD38 antibody (e.g., daratumumab) alone or in combination, and is refractory to an IMiD (i.e., lenalidomide or pomalidomide), and to a proteasome inhibitor (i.e., bortezomib, ixazomib or carfilzomib). The number of prior lines of therapy will be determined according to the guidelines in Rajkumar 2015.
5. Has measurable disease with at least one of the following:
a. Serum M-protein =0.5 g/dL (=5 g/L)
b. Urine M-protein =200 mg/24h
c. Serum FLC assay: Involved FLC level =10 mg/dL (=100 mg/L) and an abnormal serum free light chain ratio (<0.26 or >1.65)
6. Participants with a history of autologous stem cell transplant are eligible for study participation provided the following eligibility criteria are met:
a. transplant was >100 days prior to study enrolment
b. no active infection(s)
c. participant meets the remainder of the eligibility criteria outlined in this protocol
7. Adequate organ system functions as defined in Table 9 of the protocol p54.
8. Female Participants: Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
- Is not a woman of childbearing potential (WOCBP)
OR
- Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency, during the intervention period and for at least 80 days after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.
A WOCBP must have a negative highly sensitive serum pregnancy test (as required by local regulations) within 72 hours before the first dose of study intervention. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
9. Male Participants: Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Male participants are eligible to participate if they agree to the following during the intervention period and for at least 140 days:
- Refrain from donating sperm
PLUS either:
- Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent.
OR
- Must agree to use contraception/barrier as detailed below:
Agree to use a male condom and female par

Exclusion Criteria

Participants satisfying any of these criteria are not eligible for assignment to treatment:
1. Systemic anti-myeloma therapy within <14 days, or plasmapheresis within 7 days prior to the first dose of study drug
2. Symptomatic amyloidosis, active ‘polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes’ (POEMS) syndrome, active plasma cell leukemia at the time of screening.
3. Prior allogeneic stem cell transplant
4. Current corneal epithelial disease except mild punctate keratopathy
5. Use of an investigational drug within 14 days or five half-lives, whichever is shorter, preceding the first dose of study drug. Prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drugs. Prior BCMA targeted therapy.
6. Evidence of active mucosal or internal bleeding
7. Any major surgery within the last four weeks
8. Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect participant’s safety). Participants with isolated proteinuria resulting from MM are eligible, provided they fulfil criteria given in Table 9 within the protocol p54
9. Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (including lab abnormalities) that could interfere with participant’s safety, obtaining informed consent or compliance to the study procedures.
10. 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.
11. Malignancies other than disease under study are excluded, except for any other malignancy from which the participant has been disease-free for more than 2 years and, in the opinion of the principal investigators and GSK Medical Monitor, will not affect the evaluation of the effects of this clinical trial treatment on the currently targeted malignancy (MM).
12. Evidence of cardiovascular risk including any of the following:
a. QTcF interval =470 msecs (the QT interval values must be corrected for heart rate by Fridericia’s formula [QTcF])
b. Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant ECG abnormalities such as 2nd degree (Type II) or 3rd degree atrioventricular (AV) block.
c. History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within six months of Screening.
d. Class III or IV heart failure as defined by the New York Heart Association functional classification system [NYHA, 1994]
e. Uncontrolled hypertension
13. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to GSK2857916, or any of the components of the study treatment.
14. Pregnant or lactating female.
15. Active infection requiring antibiotic, antiviral, or antifungal treatment.
16. Known HIV infection.
17. 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
18. 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 trea

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified