GSK2857916 + Pomalidomide + Dexamethasone for Multiple Myeloma

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

120 Participants Needed

Trial Summary

What is the purpose of this trial?

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 with PO pomalidomide and low-dose PO dexamethasone in subjects with relapsed and/or refractory MM.

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.

What data supports the effectiveness of the drug combination GSK2857916, Pomalidomide, and Dexamethasone for treating multiple myeloma?

Research shows that Pomalidomide combined with low-dose Dexamethasone is effective in treating relapsed and refractory multiple myeloma, improving survival rates and response rates in patients who have tried other treatments. This combination is well-tolerated and offers a valuable option for patients with limited treatment choices. ^{1 2 3 4 5}

Is the combination of GSK2857916, Pomalidomide, and Dexamethasone safe for treating multiple myeloma?

The combination of Pomalidomide and low-dose Dexamethasone has been studied in multiple trials for treating relapsed and refractory multiple myeloma, showing a manageable safety profile. Common side effects include low blood cell counts (neutropenia, anemia, thrombocytopenia), infections, and fatigue, but these are generally considered manageable. ^{1 2 3 6 7}

What makes the drug GSK2857916 + Pomalidomide + Dexamethasone unique for treating multiple myeloma?

This treatment combines GSK2857916, a novel antibody-drug conjugate targeting BCMA (B-cell maturation antigen), with Pomalidomide and Dexamethasone, which are known to be effective in patients who have relapsed or are resistant to other treatments. The combination aims to enhance the immune system's ability to fight cancer cells and may offer a new option for patients with limited treatment choices. ^{1 2 3 4 8}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 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]

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]

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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

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

2. New Zealand pubmed.ncbi.nlm.nih.gov

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

3. Italy 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. [2022]

4. United States 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. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Pomalidomide (CC4047) plus low dose dexamethasone (Pom/dex) is active and well tolerated in lenalidomide refractory multiple myeloma (MM). [2022]

6. England pubmed.ncbi.nlm.nih.gov

Pomalidomide-dexamethasone in refractory multiple myeloma: long-term follow-up of a multi-cohort phase II clinical trial. [2019]

7. United States 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. [2021]

8. England 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. [2018]