GSK2857916 + Pomalidomide + Dexamethasone for Multiple Myeloma

Not currently recruiting at 8 trial locations

Overseen By Aniba Khan

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Canadian Myeloma Research Group

Must be taking: Acetylsalicylic acid

Must not be taking: Pomalidomide, BCMA therapy

Disqualifiers: Pregnancy, Uncontrolled hypertension, Active infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 56

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with multiple myeloma, a type of blood cancer, who have not responded to other treatments. The study aims to determine if adding GSK2857916 (an experimental treatment) to pomalidomide and dexamethasone is safe and effective in slowing or stopping the cancer. Individuals who have undergone multiple myeloma treatments and continue to experience disease progression might be suitable candidates, particularly if they have had stem cell transplants or are ineligible for them. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in participants and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you must be able to take acetylsalicylic acid (ASA) daily as a preventive measure, and you cannot have used pomalidomide or BCMA therapy before. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of GSK2857916 (belantamab mafodotin), pomalidomide, and dexamethasone has been studied before. These studies suggest that this treatment might benefit people with multiple myeloma, particularly if the disease has returned or hasn't responded to other treatments.

Some information about safety is available. Earlier trials reported that this combination can cause side effects, but most are manageable. Common side effects include vision changes, low blood counts, and tiredness. More serious side effects are less common but can occur.

Testing this treatment combination in more people now suggests it is considered safe enough for further study, indicating it has already undergone basic safety testing.

While this does not eliminate all risks, it provides some reassurance that the treatment has been checked for safety to some extent. Always consult a healthcare provider to determine if joining a trial is appropriate. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for multiple myeloma?

Researchers are excited about GSK2857916 for multiple myeloma because it offers a novel approach by targeting a protein called BCMA (B-cell maturation antigen) on the surface of myeloma cells, which is not a focus of current standard treatments like bortezomib or lenalidomide. This targeted action can potentially improve treatment effectiveness and reduce damage to healthy cells. Additionally, GSK2857916 is combined with pomalidomide and dexamethasone, which are known to boost the immune response against myeloma cells, offering a powerful combination that might work better than existing therapies.

What evidence suggests that this treatment might be an effective treatment for multiple myeloma?

This trial will evaluate the combination of GSK2857916 (belantamab mafodotin), pomalidomide, and dexamethasone for treating multiple myeloma. Studies have shown that this combination is promising, helping patients experience longer periods without disease progression and providing more lasting benefits compared to other treatments. Specifically, patients in these studies demonstrated significant improvements in progression-free survival, living longer without their cancer worsening. Early trials reported strong responses and promising overall survival rates for those with relapsed multiple myeloma. Overall, the evidence supports that this combination could effectively manage multiple myeloma. ^{2 5 6 7 8}

Are You a Good Fit for This Trial?

Adults with relapsed or refractory Multiple Myeloma who've had at least two prior treatments including lenalidomide and a proteasome inhibitor, can take oral medications, use effective contraception, and have no severe medical conditions that could affect safety. They must not be pregnant, have used certain myeloma therapies before, or have serious heart problems.

Inclusion Criteria

I can take pills by mouth.

Your blood test for liver function shows ALT levels within a certain range.

I can care for myself and am up and about more than 50% of my waking hours.

Exclusion Criteria

I haven't taken any experimental drugs or monoclonal antibodies recently.

Your heart's electrical activity takes longer than normal to recharge between beats.

I am currently on treatment for an active infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Finding (Part 1)

Determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of GSK2857916 in combination with pomalidomide and dexamethasone

9 months

Visits every 28-day cycle

Expansion (Part 2)

Evaluate the safety and efficacy of GSK2857916 at the RP2D in combination with pomalidomide and dexamethasone

Until disease progression or unacceptable toxicity

Visits every 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 36 months

Follow-up by phone or in person

What Are the Treatments Tested in This Trial?

Interventions

• Dexamethasone
• GSK2857916
• Pomalidomide

Trial Overview The trial is testing the combination of GSK2857916 (an IV drug), Pomalidomide (a pill), and low-dose Dexamethasone (also a pill) to see if they're safe together and work well for treating Multiple Myeloma in patients who haven't responded to other treatments.

How Is the Trial Designed?

Group I: GSK2857916 with Pomalidomide and Dexamethasone Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Canadian Myeloma Research Group

Lead Sponsor

Trials

7

Recruited

500+

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Published Research Related to This Trial

Pomalidomide, combined with low-dose dexamethasone, has been shown to be effective in treating adult patients with relapsed and refractory multiple myeloma, significantly improving progression-free survival and overall response rates compared to high-dose dexamethasone.

The treatment demonstrated a manageable safety profile and was effective across various patient subgroups, including those who were refractory to previous therapies, indicating its potential as a valuable salvage therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide: a review of its use in patients with recurrent multiple myeloma. Scott, LJ.[2022]

In a phase 3 trial involving 455 patients with refractory or relapsed multiple myeloma, pomalidomide combined with low-dose dexamethasone significantly improved progression-free survival and overall survival compared to high-dose dexamethasone.

The treatment was effective across all patient subgroups, regardless of their previous treatments, and showed no cross-resistance with prior therapies, making it a strong candidate for standard care in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed/refractory multiple myeloma. San Miguel, JF., Weisel, KC., Song, KW., et al.[2022]

Pomalidomide combined with dexamethasone (PomDex) shows strong anti-cancer effects in both lenalidomide-sensitive and resistant multiple myeloma cell lines, indicating its potential as an effective treatment option for patients who have not responded to other therapies.

The combination therapy not only inhibits tumor growth more effectively than single-agent treatments but also induces apoptosis through specific molecular mechanisms, such as the degradation of IKZF3 and modulation of pro-apoptotic pathways, particularly in lenalidomide-resistant cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide in combination with dexamethasone results in synergistic anti-tumour responses in pre-clinical models of lenalidomide-resistant multiple myeloma. Rychak, E., Mendy, D., Shi, T., et al.[2018]

In a clinical trial involving 345 patients with refractory multiple myeloma, the combination of pomalidomide and dexamethasone (Pom/dex) showed a confirmed response rate of 35%, with better outcomes in patients who had undergone fewer prior treatments.

The study found that the 2 mg dose of pomalidomide resulted in longer treatment durations, higher response rates, and fewer adverse events, with median progression-free survival of 13.1 months and overall survival of 47.9 months, indicating its potential effectiveness in managing this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide-dexamethasone in refractory multiple myeloma: long-term follow-up of a multi-cohort phase II clinical trial. Ailawadhi, S., Mikhael, JR., LaPlant, BR., et al.[2019]

Pomalidomide, when combined with low-dose dexamethasone, significantly improves progression-free survival and overall survival in adults with relapsed and refractory multiple myeloma, based on results from multinational phase II and III studies involving patients who had undergone at least two prior treatments.

The treatment has a manageable safety profile, with the most common serious side effects being neutropenia, infections, anemia, and thrombocytopenia, making it a viable option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide: A Review in Relapsed and Refractory Multiple Myeloma. Hoy, SM.[2018]

Pomalidomide, combined with weekly dexamethasone, shows promising efficacy in patients with multiple myeloma who have not responded to lenalidomide and bortezomib, achieving an overall response rate of 49% at 2 mg and 43% at 4 mg daily.

The treatment demonstrated a 6-month overall survival rate of 78% for the 2 mg cohort and 67% for the 4 mg cohort, with myelosuppression being the most common side effect, indicating that while effective, careful monitoring for toxicity is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide plus low-dose dexamethasone in myeloma refractory to both bortezomib and lenalidomide: comparison of 2 dosing strategies in dual-refractory disease. Lacy, MQ., Allred, JB., Gertz, MA., et al.[2021]

The STRATUS study, involving 682 patients with relapsed and/or refractory multiple myeloma, demonstrated that the combination of pomalidomide and low-dose dexamethasone resulted in a 32.6% overall response rate, indicating its efficacy in this difficult-to-treat population.

The treatment was generally well tolerated, with the most common severe side effects being hematologic issues like neutropenia and anemia, but serious complications like venous thromboembolism were rare, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of pomalidomide plus low-dose dexamethasone in STRATUS (MM-010): a phase 3b study in refractory multiple myeloma. Dimopoulos, MA., Palumbo, A., Corradini, P., et al.[2021]

In a study of 34 lenalidomide-refractory multiple myeloma patients, the combination of pomalidomide and dexamethasone showed a 47% overall response rate, with some patients achieving very good partial responses and partial responses.

The treatment was well tolerated, although 53% of patients experienced significant hematologic toxicity, including anemia and neutropenia, indicating that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide (CC4047) plus low dose dexamethasone (Pom/dex) is active and well tolerated in lenalidomide refractory multiple myeloma (MM). Lacy, MQ., Hayman, SR., Gertz, MA., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38828951/

Belantamab Mafodotin, Pomalidomide, and ... BPd conferred a significantly greater benefit than PVd with respect to progression-free survival, as well as deeper, more durable responses.

2. nejm.org nejm.org/doi/abs/10.1056/NEJMoa2403407

Belantamab Mafodotin, Pomalidomide, and ... BPd conferred a significantly greater benefit than PVd with respect to progression-free survival, as well as deeper, more durable responses.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.17_suppl.LBA105

Results from the randomized phase 3 DREAMM-8 study of ... The DREAMM-8 study demonstrated a statistically significant and clinically meaningful PFS benefit with BPd vs PVd in RRMM with >1 prior LoT.

4. nature.com nature.com/articles/s41591-023-02703-y

a phase 1/2 trial Belantamab mafodotin plus pomalidomide and dexamethasone induced durable responses with promising overall survival in relapsed multiple myeloma.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04484623

Study Details | NCT04484623 | Belantamab Mafodotin Plus ... This study will evaluate the efficacy and safety of belantamab mafodotin in combination with pomalidomide and dexamethasone (Arm A)

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03715478

NCT03715478 | Multi-Center Study of GSK2857916 in ... 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 ...

7. gsk.com gsk.com/en-gb/media/press-releases/blenrep-combinations-accepted-for-review-by-the-us-fda-for-the-treatment-of-relapsedrefractory-multiple-myeloma/

Blenrep combinations accepted for review by the US FDA ... Blenrep shows overall survival benefit in head-to-head DREAMM-7 phase III trial for relapsed/refractory multiple myeloma. Available at ...

8. gskpro.com gskpro.com/en-gb/products/blenrep/dreamm-8/efficacy-and-safety/

BLENREP + Pd: Clinical trial efficacy & safety data | GSK UK Review the BLENREP (belantamab mafodotin) + Pd efficacy and safety data from the Phase III DREAMM-8 trial. For UK HCPs only.