| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Relapsed/Refractory Multiple Myeloma |
|
| E.1.1.1 | Medical condition in easily understood language |
| Relapsed/Refractory Multiple Myeloma |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10028228 |
| E.1.2 | Term | Multiple myeloma |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the clinical efficacy of 2 doses of belantamab mafodotin in participants with relapsed/refractory multiple myeloma |
|
| E.2.2 | Secondary objectives of the trial |
- To further evaluate the clinical measures of efficacy of belantamab mafodotin in participants with RRMM
- To evaluate the safety of belantamab mafodotin in participants with RRMM.
- To evaluate the pharmacokinetic profile of belantamab mafodotin
- To assess anti-drug antibodies (ADAs) against belantamab mafodotin
- Participant self-reported symptomatic adverse effects by evaluation of tolerability of belantamab mafodotin
- To evaluate disease and treatment related symptoms and impact on function and health-related quality-of-life |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Full title:
Protocol Title: A Phase II, Open Label, Randomized, Two-Arm Study to Investigate the
Efficacy and Safety of Two Doses of the Antibody Drug Conjugate GSK2857916 in
Participants with Multiple Myeloma Who Had 3 or More Prior Lines of Treatment, Are
Refractory to a Proteasome Inhibitor and an Immunomodulatory Agent and Have Failed
an Anti-CD38 Antibody (DREAMM 2)
Date and version:
05
Objective:
To evaluate the effect of topical corticosteroids on corneal findings in approximately 30 participants who will receive monocular topical corticosteroids for the first 4 cycles |
|
| E.3 | Principal 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 (e.g., 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 p55.
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 partner to use an additional highly effective contraceptive method with a failure rate of <1% per year as when having sexual intercourse with a woman of childbearing potential who is not currently pregnant.
10. All prior treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4.03, must be ≤Grade 1 at the time of enrolment except for alopecia and Grade 2 peripheral neuropathy.
11. (France only) A participant will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category. |
|
| E.4 | Principal exclusion criteria |
Participants satisfying any of these criteria are not eligible for assignment to treatment:
1. Systemic anti-myeloma therapy within ≤14 days or 5 half-lives, whichever is shorter, or plasmapheresis within 7 days prior to the first dose of study drug
2. Systemic treatment with high dose steroids (equivalent to ≥60 mg prednisone daily for ≥4 days) within the past 14 days if administered to treat MM or non-MM disease
3. Symptomatic amyloidosis, active ‘polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes’ (POEMS) syndrome, active plasma cell leukemia at the time of screening.
4. Prior allogeneic stem cell transplant
5. Current corneal epithelial disease except mild punctate keratopathy
6. 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.
7. Evidence of active mucosal or internal bleeding
8. Any major surgery within the last four weeks
9. 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 p55
10. 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.
11. 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.
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 (MM). Participants with curatively treated non-melanoma skin cancer may be enrolled.
13. Evidence of cardiovascular risk including any of the following:
a. QTcF interval > 480 msec(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
14. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to belantamab mafodotin, or any of the components of the study treatment.
15. Pregnant or lactating female.
16. Active infection requiring antibiotic, antiviral, or antifungal treatment.
17. Known HIV infection.
18. 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
19. 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. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| ORR, defined as the percentage of participants with a confirmed partial response (PR) or better (i.e., PR, very good partial response [VGPR], complete response [CR] and stringent complete response [sCR]), according to the 2016 International Myeloma Working Group (IMWG) Response Criteria by Independent Review Committee (IRC). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
ORR, defined as the percentage of participants with a confirmed partial
response (PR) or better, according to the 2016 International Myeloma
Working Group (IMWG) Response Criteria by investigator assessment.
Clinical benefit rate (CBR), defined as the percentage of participants with a confirmed minimal response (MR) or better according to the 2016 International Myeloma Working Group (IMWG) Response Criteria.
Duration of response (DoR), defined as: the time from first documented evidence of PR or better until the earliest date of documented disease progression (PD) per IMWG; or death due to PD occurs among participants who achieve an overall response, i.e., confirmed PR or better.
Time to response, defined as the time between the date of randomization and the first documented evidence of response (PR or better).
Progression-free survival, defined as the time from randomization until the earliest date of documented disease progression (PD) per IMWG, or death due to any cause.
Time to progression, defined as the time from randomization until the earliest date of documented PD per IMWG, or death due to PD.
Overall survival, defined as the time from randomization until death due to any cause.
The safety profile of belantamab mafodotin will be evaluated in participants with RRMM as assessed through: standard clinical and laboratory tests (hematology and chemistry,
physical examination, vital sign measurements, and diagnostic tests) through the collection of adverse events (AEs) and serious adverse events (SAEs) AEs of special interest ocular findings on ophthalmic exam
Plasma concentrations of belantamab mafodotin (ADC, total mAb and cys-mcMMAF)
Derived pharmacokinetic parameter values (e.g., AUC, Cmax, tmax, t½), as data permit.
Incidence and titers of ADAs against belantamab mafodotin
Symptomatic adverse effects and related impacts as measured by the PRO-CTCAE, NEI-VFQ-25 and OSDI
Health-related quality-of-life as measured by the EORTC QLQ-C30 and EORTC QLQ-MY20 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Response assessments will be every 3 weeks or as clinically indicated. After discontinuation of treatment PFS will be every 3 weeks and OS will be every 3 months. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 34 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Canada |
| France |
| Germany |
| Italy |
| Spain |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 8 |
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