Open-label single-arm study of GSK2857916 in combination with Pembrolizumab in subjects with relapsed/refractory multiple myeloma

Phase 1

• Conditions: Relapsed/Refractory Multiple Myeloma; MedDRA version: 20.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-002816-29-ES
• Lead Sponsor: GlaxoSmithKline, S.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-04-11
• Last Update Posted: 26 September 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 41

Inclusion Criteria

Subjects eligible for enrolment in the study must meet all of the following criteria:
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 or 1 (Appendix 2 of the protocol)
4. Subjects must:
-Has histologically or cytologically confirmed diagnosis of MM, as defined by IMWG, 2014 [Rajkumar, 2014], and
-Has undergone stem cell transplant or is considered transplant ineligible, and
- Has been treated with at least 3 prior lines of prior anti-myeloma treatments including an IMiD (eg. lenalidomide or pomalidomide), a proteasome inhibitor (eg. bortezomib, ixazomib or carfilzomib) and an anti-CD38 antibody alone or in combination. Line of therapy are defined by consensus panel of the
International Myeloma Workshop [Rajkumar, 2011].
-Has measurable disease defined as one 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)
5. Subjects 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) subject meets the remainder of the eligibility criteria outlined in this
protocol
6. Adequate organ system functions as defined in Table 3 of the study protocol
7. All prior treatment-related toxicities (defined by National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4.03, 2010) [NCI, 2010] must be = Grade 1 at the time of enrollment except for alopecia and Grade 2 neuropathy.
8. A female subject 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, as described in Appendix 8 of the protocol during the intervention period and for at least 120 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.
Additional requirements for pregnancy testing during and after study intervention are located in Appendix 8 of the protocol.
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 subjects:
Male subjects are eligible to participate if they agree to the following during the intervention period and for at least 140 days after the last dose of study intervention:
-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

Exclusion Criteria

A subject will not be eligible for inclusion in this study if any of the following criteria apply:
1. Systemic anti-myeloma therapy or an investigational drug =14 days or five half-lives, whichever is shorter, preceding the first dose of study drug
2. Plasmapheresis within 7 days prior to the first dose of study drug
3. Prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drugs
4. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137) and was discontinued from that treatment due to a Grade 3 or higher immune related adverse event (irAE)
5. Current corneal epithelial disease except mild punctate keratopathy
6. Any major surgery within the last four weeks prior to the first dose of study therapy
7. Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect subject’s safety). Subjects with isolated proteinuria resulting from MM are eligible, provided they fulfill criteria given in Table 3 of the protocol
8. 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.
9. Has received prior radiotherapy within 2 weeks of start of study therapy. Subjects must have recovered from all radiation-related toxicities, not requite corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=2 weeks of radiotherapy) to non-CNS disease.
10. History of (non-infectious) pneumonitis that required steroids, or current pneumonitis
11. Current active 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 subject otherwise meets entry criteria
12. 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 (RRMM). Subjects with curatively treated non-melanoma skin cancer are allowed.
13. Has known active CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study therapy
14. Evidence of cardiovascular risk including any of the following:
a. QTcF interval =470 msecs.
NOTE: The QT interval should be corrected for heart rate by Fridericia’s formula (QTcF).
b. Evidence of current clinically significant uncontrolled arrhythmias;
i. including clinically significant ECG abnormalities including 2nd degree
(Type II) or 3rd degree atrioventricular (AV) block.
c. Histor

Study & Design

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