Phase 2
Completed N=41
Study Evaluating Safety, Tolerability and Clinical Activity of GSK2857916 in Combination With Pembrolizumab in Subjects With Relapsed/Refractory Multiple Myeloma (RRMM)
Source: ClinicalTrials.gov NCT03848845 ↗Enrolled (actual)
41
Serious AEs
32.6%
Results posted
Dec 2022
Primary outcomePrimary: Part 1 - Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) — 6; 7; 4; 5 Participants
Summary
This is a phase I/II, single arm, open label, two-part study that will assess safety, tolerability and clinical activity of GSK2857916 given in combination with a programmed cell death-1 (PD-1) inhibitor pembrolizumab in subjects with RRMM. This study will enroll adult subjects with RRMM, who have undergone stem cell transplant or who are considered transplant ineligible. Part 1 is a dose escalation phase to evaluate the safety and tolerability of escalating doses of GSK2857916 in combination with 200 milligrams (mg) pembrolizumab to establish the recommended phase 2 dose (RP2D). The following dose levels of GSK2857916 are planned to be studied: 2.5 milligrams per kilograms (mg/kg) (dose level [DL] 1) and 3.4 mg/kg (DL2). Part 2 is a dose expansion cohort. Once the RP2D has been identified, an expansion cohort will open for enrolment to confirm the safety profile and to evaluate the clinical activity of the combination. Up to 40 evaluable subjects will be enrolled in this two-part study (up to 12 in Part 1, and 28 in Part 2).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1 - Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
6; 7; 4; 5 | — |
| PRIMARY Part 1 - Number of Participants With Dose Limiting Toxicities (DLTs) |
0; 0 | — |
| PRIMARY Part 1 - Number of Participants With Worst-case Grade Change From Baseline in Hematology Parameters |
4; 2; 3; 1; 0; 0 | — |
| PRIMARY Part 1 - Number of Participants With Worst-case Change Post-baseline in Hematology Parameters |
0; 0; 6; 6; 0; 0 | — |
| PRIMARY Part 1 - Number of Participants With Worst-case Grade Change From Baseline in Lab Chemistry Parameters |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part 1 - Number of Participants With Worst-case Change Post-baseline in Lab Chemistry Parameters |
1; 2; 4; 4; 1; 1 | — |
| PRIMARY Part 1 - Number of Participants With Worst-case Change Post-baseline Urinalysis Results |
6; 5; 0; 1; 3; 5 | — |
| PRIMARY Part 1 - Changes From Baseline in Urine Potential of Hydrogen (pH) |
1.0; 0.0 | — |
| PRIMARY Part 1 - Changes From Baseline in Urine Specific Gravity |
-0.0010; 0.0100 | — |
| PRIMARY Part 1 - Number of Participants With Worst-case Grade Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) |
6; 4; 2; 1; 0; 0 | — |
| PRIMARY Part 1 - Number of Participants With Worst-case Change From Baseline in Vital Signs: Pulse Rate and Body Temperature |
3; 2; 3; 3; 0; 2 | — |
| PRIMARY Part 2 - Percentage of Participants With Overall Response Rate (ORR) |
43 | — |
| SECONDARY Part 1 - Percentage of Participants With Overall Response Rate (ORR) |
67; 43 | — |
| SECONDARY Part 2 - Number of Participants With AEs and SAEs |
27; 5 | — |
| SECONDARY Part 2 - Number of Participants With Worst-case Grade Change From Baseline in Hematology Parameters |
10; 3; 0; 2; 0; 0 | — |
| SECONDARY Part 2 - Number of Participants With Worst-case Change Post-baseline in Hematology Parameters |
0; 22; 1; 2; 22; 3 | — |
| SECONDARY Part 2 - Number of Participants With Worst-case Grade Change From Baseline in Lab Chemistry Parameters |
1; 0; 0; 4; 0; 0 | — |
| SECONDARY Part 2 - Number of Participants With Worst-case Change Post-baseline in Lab Chemistry Parameters |
4; 18; 5; 4; 14; 9 | — |
| SECONDARY Part 2 - Number of Participants With Worst-case Change Post-baseline Urinalysis Results |
25; 1; 21; 5; 15; 9 | — |
| SECONDARY Part 2 - Changes From Baseline in Urine Specific Gravity |
1.0171; -0.0001 | — |
| SECONDARY Part 2 - Changes From Baseline in Urine pH |
5.71; 0.10 | — |
| SECONDARY Part 2 - Number of Participants With Worst-case Grade Change From Baseline in Vital Signs: DBP and SBP |
20; 12; 2; 24; 16; 6 | — |
| SECONDARY Part 2 - Number of Participants With Worst-case Change From Baseline in Vital Signs: Pulse Rate and Body Temperature |
10; 11; 7; 2; 23; 3 | — |
| SECONDARY Part 2 - Number of Participants With Maximum Worst-case Change From Baseline in Best Corrected Visual Acuity Test (BCVA) Scores |
14; 5; 8; 16; 4; 7 | — |
| SECONDARY Part 2 - Time Taken for the Onset of First Occurrence of Worsening in BCVA Score |
78.0 | — |
| SECONDARY Part 2 - Outcome of First Occurrence of Worsening Eye in BCVA Score |
7; 2; 1 | — |
| SECONDARY Part 2 - Duration of First Occurrence of Worsening in BCVA Score |
47.0 | — |
| SECONDARY Part 2 - Number of Participants According to the Number of Definite Events of Worsening of Vision |
6; 1; 3 | — |
| SECONDARY Part 2 - Number of Participants With Resolution of Post Treatment Exposure Worsening in BCVA Score |
2; 0; 2 | — |
| SECONDARY Part 2 - Duration of Resolution Post-treatment Exposure of Worsening in BCVA Score |
34.5 | — |
| SECONDARY Part 2 - Number of Participants With Post-baseline Decline in BCVA to Light Perception or no Light Perception |
— | — |
| SECONDARY Part 2 - Number of Participants With Worst-case Shift From Baseline in Ophthalmological Epithelium Exam |
3; 16; 0; 8; 0; 1 | — |
| SECONDARY Part 2 - Number of Participants With Worst-case Shift From Baseline in Corneal Examinations |
23; 0; 1; 0; 0; 0 | — |
| SECONDARY Part 2 - Number of Participants With Worse Case Post-baseline Punctate Keratopathy Findings |
2; 11; 7; 6; 2; 9 | — |
| SECONDARY Part 2 - Number of Participants With Worst-case Shift From Baseline in Lens Examinations |
12; 0; 3; 3; 10; 0 | — |
| SECONDARY Part 2 - Percentage of Participants With Clinical Benefit Rate |
43 | — |
| SECONDARY Part 2 - Duration of Response |
7.6 | — |
| SECONDARY Part 2 - Time to Response |
0.7 | — |
| SECONDARY Part 2 - Time to Best Response |
1.7 | — |
| SECONDARY Part 2 - Progression-free Survival |
2.5 | — |
| SECONDARY Part 2 - Time to Disease Progression |
2.5 | — |
| SECONDARY Part 2 - Overall Survival |
NA | — |
| SECONDARY Part 1 - Maximum Concentration (Cmax) for Belantamab Mafodotin After First Dose |
— | — |
| SECONDARY Part 2 - Cmax for Belantamab Mafodotin After First Dose |
— | — |
| SECONDARY Part 1 - End of Infusion Concentration (C-EOI) for Belantamab Mafodotin |
— | — |
| SECONDARY Part 2 - C-EOI for Belantamab Mafodotin |
— | — |
| SECONDARY Part 1 - Time of Cmax (Tmax) for Belantamab Mafodotin After First Dose |
— | — |
| SECONDARY Part 2 - Tmax for Belantamab Mafodotin After First Dose |
— | — |
| SECONDARY Part 1 - Trough Concentration Prior to the Next Dose for Each Cycle (Ctrough) for Belantamab Mafodotin |
— | — |
| SECONDARY Part 2 - Ctrough for Belantamab Mafodotin |
— | — |
| SECONDARY Part 1 - Last Time Point Where the Concentration is Above the Limit of Quantification (Tlast) for Belantamab Mafodotin After First Dose |
— | — |
| SECONDARY Part 2 - Tlast for Belantamab Mafodotin After First Dose |
— | — |
| SECONDARY Part 1 - Area Under Plasma Concentration-time Curve (AUC) From Time 0 to End of the Dosing Interval [AUC (0-tau)] for Belantamab Mafodotin After First Dose |
— | — |
| SECONDARY Part 2 - AUC (0-tau) for Belantamab Mafodotin After First Dose |
— | — |
| SECONDARY Part 1 - Cmax for Total Monoclonal Antibody (mAb) After First Dose |
43.57; 64.45 | — |
| SECONDARY Part 2 - Cmax for Total mAb After First Dose |
46.70 | — |
| SECONDARY Part 1 - C-EOI for Total mAb |
40.15; 65.30; 53.90; 64.65; 54.65; 73.90 | — |
| SECONDARY Part 2 - C-EOI for Total mAb |
48.60; 53.00; 52.35 | — |
| SECONDARY Part 1 - Tmax for Total mAb After First Dose |
1.100; 1.520 | — |
| SECONDARY Part 2 - Tmax for Total mAb After First Dose |
0.945 | — |
| SECONDARY Part 1 - Ctrough for Total mAb |
5.420; 13.350; 8.91; 18.80; 26.90; 45.05 | — |
| SECONDARY Part 2 - Ctrough for Total mAb |
7.735; 11.60 | — |
| SECONDARY Part 1 - Last Time Point Where the Concentration is Above the Limit of Quantification (Tlast) for Total mAb After First Dose |
501.800; 481.580 | — |
| SECONDARY Part 2 - Tlast for Total mAb After First Dose |
503.140 | — |
| SECONDARY Part 1 - AUC (0-tau) for Total mAb After First Dose |
6237.2; 10817.8 | — |
| SECONDARY Part 2 - AUC (0-tau) for Total mAb After First Dose |
7949.0 | — |
| SECONDARY Part 1 - Cmax for Cysteine Maleimidocaproyl Monomethyl Auristatin F (Cys-mcMMAF) After First Dose |
1.5799; 1.0966 | — |
| SECONDARY Part 2 - Cmax for Cys-mcMMAF After First Dose |
1.2481 | — |
| SECONDARY Part 1 - C-EOI for Cys-mcMMAF After First Dose |
0.7110; 0.7630 | — |
| SECONDARY Part 2 - C-EOI for Cys-mcMMAF After First Dose |
0.3150 | — |
| SECONDARY Part 1 - Tmax for Cys-mcMMAF After First Dose |
13.510; 4.120 | — |
| SECONDARY Part 2 - Tmax for Cys-mcMMAF After First Dose |
23.580 | — |
| SECONDARY Part 1 - Tlast for Cys-mcMMAF After First Dose |
161.380; 171.250 | — |
| SECONDARY Part 2 - Tlast for Cys-mcMMAF After First Dose |
167.510 | — |
| SECONDARY Part 1 - AUC From Time 0 to 168 h After Dosing [AUC (0-168h)] for Cys-mcMMAF After First Dose |
155.27; 90.61 | — |
| SECONDARY Part 2 - AUC (0-168 h) for Cys-mcMMAF After First Dose |
128.38 | — |
| SECONDARY Part 1 - Cmax for Pembrolizumab After First Dose |
— | — |
| SECONDARY Part 2 - Cmax for Pembrolizumab After First Dose |
— | — |
| SECONDARY Part 1 - Tmax for Pembrolizumab After First Dose |
— | — |
| SECONDARY Part 2 - Tmax for Pembrolizumab After First Dose |
— | — |
| SECONDARY Part 1 - AUC (0-tau) for Pembrolizumab After First Dose |
— | — |
| SECONDARY Part 2 - AUC (0-tau) for Pembrolizumab After First Dose |
— | — |
| SECONDARY Part 1 - Number of Participants With Post-baseline Positive Anti-drug Antibodies (ADAs) Against Belantamab Mafodotin |
0; 0; 0; 0 | — |
| SECONDARY Part 2 - Number of Participants With Post-baseline Positive ADAs Against Belantamab Mafodotin |
0; 0 | — |
| SECONDARY Part 1 - Titers of ADAs Against Belantamab Mafodotin |
— | — |
| SECONDARY Part 2 - Titers of ADAs Against Belantamab Mafodotin |
— | — |
Eligibility Criteria
Inclusion criteria
- Provide signed written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- Male or female, 18 years or older (at the time consent is obtained).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Subjects must: have histologically or cytologically confirmed diagnosis of Multiple myeloma (MM), as defined by IMWG, 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 immunomodulatory imide drug (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, Has measurable disease defined as one the following: a) Serum M-protein >=0.5 grams per deciliter (g/dL) (>=5 grams per liter [g/L]). b) Urine M-protein ≥200 mg/24h. c) Serum Free light chain (FLC) assay: Involved FLC level ≥10 milligrams per deciliter (mg/dL) (≥100 milligrams per liter [mg/L]) and an abnormal serum free light chain ratio ( 1.65).
- 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.
- Adequate organ system functions as defined by the laboratory assessments.
- All prior treatment-related toxicities (defined by National Cancer Institute-Common Toxicity Criteria for Adverse Events [NCI-CTCAE], version 4.03, 2010) must be =Grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study). Subjects with moderate valvular thickening should not be entered on study.
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to GSK2857916 or pembrolizumab, or any of the components of the study treatment.
- Pregnant or lactating female.
- Known active infection requiring antibiotic, antiviral, or antifungal treatment.
- Known Human Immunodeficiency Virus (HIV) infection.
- 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
- Positive hepatitis C antibody test result or positive hepatitis C Ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment.
- Has received a live-virus vaccination within 30 days of planned start of study therapy.
- Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other chronic form of immunosuppressive therapy within 7 days prior the first dose of study therapy.
- Has known psychiatric or substance abuse disorder that would interfere with the subject's ability to cooperate with the requirements of the study.
- Has had an allogenic tissue/solid organ transplant
Data sourced from ClinicalTrials.gov (NCT03848845). 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.