JNJ-87562761 for Multiple Myeloma

Recruiting at 5 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Janssen Research & Development, LLC

Must be taking: Proteasome inhibitors, Immunomodulatory agents

Must not be taking: Corticosteroids, Monoclonal antibodies

Disqualifiers: Plasma cell leukemia, CNS involvement, others

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

Compensation: Varies

Number of Visits: Unknown

80 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine the recommended phase 2 dose(s) (RP2D\[s\]) of JNJ-87562761 in Part 1 (dose escalation), and to determine the safety and tolerability at RP2D in Part 2 (dose expansion) in participants with multiple myeloma (MM) whose disease has come back after treatment (relapsed) or hasn't responded to treatment (refractory).

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have had certain antitumor therapies within specific time frames before starting the study treatment, such as targeted therapy, monoclonal antibody treatment, or conventional chemotherapy within 21 days, and others as listed in the exclusion criteria.

What data supports the idea that JNJ-87562761 for Multiple Myeloma is an effective treatment?

The available research does not provide specific data on the effectiveness of JNJ-87562761 for Multiple Myeloma. However, it highlights the success of other treatments like daratumumab combined with lenalidomide and dexamethasone, which showed significant improvement in patient outcomes. This suggests that new treatments, including JNJ-87562761, are being developed in a rapidly evolving field with promising potential. The research also indicates that the treatment landscape for Multiple Myeloma has improved significantly with the introduction of new therapies, leading to better survival rates. ^{1 2 3 4 5}

What safety data is available for JNJ-87562761 in treating multiple myeloma?

The provided research does not contain specific safety data for JNJ-87562761. The studies mentioned focus on other treatments for multiple myeloma, such as ruxolitinib, INCB052793, ixazomib, elotuzumab, and lenalidomide with dexamethasone. These studies report various adverse events and safety profiles for these treatments, but none specifically address JNJ-87562761. ^{6 7 8 9 10}

Is the drug JNJ-87562761 a promising treatment for Multiple Myeloma?

The drug JNJ-87562761 is promising for treating Multiple Myeloma because it targets pathways that help cancer cells grow and survive. This approach could lead to new ways to fight the disease and improve patient outcomes. ^{1 10 11 12 13}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for adults with multiple myeloma that has returned or hasn't improved after treatment. Participants must be in good physical condition (ECOG 0-1), have had specific prior therapies, measurable disease levels, and adequate kidney function. They cannot be pregnant or breastfeeding and must agree to contraception.

Inclusion Criteria

My multiple myeloma has returned or hasn't responded to treatment, and tests show it's measurable.

I am fully active or restricted in physically strenuous activity but can do light work.

My kidney function, measured by eGFR, is above 30 mL/min/1.73m^2.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive JNJ-87562761 with dose escalation to determine the recommended phase 2 dose (RP2D)

up to approximately 3 years

Dose Expansion

Participants receive JNJ-87562761 at the RP2D regimen(s) determined in Part 1

up to approximately 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to approximately 3 years

Treatment Details

Interventions

• JNJ-87562761

Trial Overview The study aims to find the optimal dose of JNJ-87562761 for phase 2 trials in part one and assess its safety at this dose in part two among patients with relapsed or refractory multiple myeloma.

Participant Groups

Group I: JNJ-87562761 Experimental Treatment 1 Intervention

Participants will receive JNJ-87562761 during the Part 1 (Dose escalation) to determine the recommended phase 2 dose (RP2D) regimen(s). The dose will be escalated sequentially until the RP2D regimen(s) have been identified. In Part 2 (Dose expansion) participants will receive JNJ-87562761 at the RP2D regimen(s) determined in Part 1.

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

The treatment landscape for multiple myeloma (MM) has significantly improved, with four new drugs approved in 2015 alone, leading to better patient outcomes than seen in any other cancer over the past decade.

Several new investigational agents, such as Isatuximab and marizomib, show promising efficacy in clinical trials, indicating a strong potential for future regulatory approval and further advancements in MM treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New investigational drugs with single-agent activity in multiple myeloma. Rajan, AM., Kumar, S.[2022]

In a pooled analysis of two large phase III trials involving 704 patients with relapsed/refractory multiple myeloma, treatment with lenalidomide plus dexamethasone resulted in a significantly higher overall response rate (60.6% vs 21.9%) and improved complete response rate (15.0% vs 2.0%) compared to dexamethasone plus placebo.

Patients receiving lenalidomide plus dexamethasone also experienced longer survival, with a median overall survival of 38.0 months compared to 31.6 months for those on dexamethasone-placebo, indicating a substantial benefit from this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Dimopoulos, MA., Chen, C., Spencer, A., et al.[2022]

From 2011 to 2019, treatment for multiple myeloma has shifted towards more combination therapies, with triplet regimens (PI-IMiD-dexamethasone) becoming the most common first-line treatment by 2018-2019, indicating a trend towards more aggressive treatment strategies.

Despite advancements in treatment, median overall survival decreased with each subsequent line of therapy, highlighting the challenges in managing multiple myeloma as the disease progresses, although survival rates improved for patients diagnosed more recently.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trends in the multiple myeloma treatment landscape and survival: a U.S. analysis using 2011-2019 oncology clinic electronic health record data. Braunlin, M., Belani, R., Buchanan, J., et al.[2021]

A systematic review and network meta-analysis of 37 randomized trials involving patients with relapsed and/or refractory multiple myeloma (MM) found that the combination of daratumumab, lenalidomide, and dexamethasone significantly improved progression-free survival compared to dexamethasone alone, with a hazard ratio of 0.13.

The study confirms the strong efficacy of three-drug regimens that include anti-CD38 antibodies, providing valuable insights for evaluating new treatments like chimeric antigen receptor T-cell therapies and bispecific T-cell engagers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relapsed and refractory multiple myeloma: A systematic review and network meta-analysis of the efficacy of novel therapies. Minakata, D., Fujiwara, SI., Yokoyama, D., et al.[2023]

The treatment of multiple myeloma has significantly improved with the introduction of more effective therapies, such as immune modulators and proteasome inhibitors, moving away from older chemotherapeutic agents.

Current and emerging immunotherapy strategies, including monoclonal antibodies, checkpoint inhibitors, vaccines, and adoptive T-cell therapies, are being integrated into standard treatment, indicating a promising future for managing this disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The immunotherapy era of myeloma: monoclonal antibodies, vaccines, and adoptive T-cell therapies. Hoyos, V., Borrello, I.[2022]

Ruxolitinib, when combined with lenalidomide and methylprednisolone, shows potential to overcome resistance to lenalidomide in patients with relapsed/refractory multiple myeloma, achieving a clinical benefit rate of 49% and an overall response rate of 36% in a Phase I trial with 49 participants.

The trial demonstrated that ruxolitinib was safe, with no dose-limiting toxicities reported, although some patients experienced grade 3 or 4 adverse events, including anemia and decreased lymphocyte count, indicating a manageable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 study of ruxolitinib, steroids and lenalidomide for relapsed/refractory multiple myeloma patients. Berenson, JR., Kim, C., Bujarski, S., et al.[2022]

In a study involving 121 patients with newly diagnosed multiple myeloma, maintenance therapy with the oral proteasome inhibitor ixazomib after induction therapy led to a significant increase in response rates, with 35% achieving a complete response after maintenance.

The safety profile of ixazomib was favorable, with only 24% of patients experiencing grade 3 or higher drug-related adverse events, indicating that ixazomib can be safely administered for long-term treatment without cumulative toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ixazomib maintenance therapy in newly diagnosed multiple myeloma: An integrated analysis of four phase I/II studies. Dimopoulos, MA., Laubach, JP., Echeveste Gutierrez, MA., et al.[2019]

Elotuzumab, when combined with lenalidomide and dexamethasone, significantly improves progression-free survival (PFS) in patients with relapsed or refractory multiple myeloma, with a median PFS of 19.4 months compared to 14.9 months for the standard treatment.

The treatment showed a higher overall response rate (ORR) of 75.8% versus 65.5% for the standard therapy, although serious adverse reactions were more common in the elotuzumab group (65% vs. 57%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Drug Approval: Elotuzumab in Combination with Lenalidomide and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma. Gormley, NJ., Ko, CW., Deisseroth, A., et al.[2018]

Lenalidomide combined with dexamethasone has been shown to be effective for treating relapsed/refractory multiple myeloma, and it has received approval from both the FDA and EMA for patients who have undergone at least one prior therapy.

The most common serious side effects include cytopenias and infections, but an expert panel has provided management strategies to minimize these risks, ensuring that patients can receive the full benefits of the treatment without unnecessary dose reductions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma. Palumbo, A., Dimopoulos, M., San Miguel, J., et al.[2018]

The selective JAK1 inhibitor INCB052793 (INCB) significantly reduced the viability of multiple myeloma (MM) cells in both patient samples and cell lines, indicating its potential as an effective treatment.

In vivo studies in mice showed that INCB not only decreased tumor growth when used alone but also enhanced the anti-tumor effects when combined with other treatments like proteasome inhibitors and glucocorticosteroids, suggesting a promising strategy for MM therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The anti-myeloma effects of the selective JAK1 inhibitor (INCB052793) alone and in combination in vitro and in vivo. Sanchez, E., Li, M., Patil, S., et al.[2019]

In a study of multiple myeloma (MM) patients, 57% showed overexpression of JAK2 and 27% showed overexpression of JAK1, suggesting that targeting these JAK proteins could be a promising therapeutic strategy.

Treatment with the JAK inhibitor ruxolitinib, combined with bortezomib and lenalidomide, resulted in 72% cell death in MM cell lines, indicating that inhibiting the JAK/STAT pathway may effectively induce apoptosis in MM cells and could serve as a new target for therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-myeloma effects of ruxolitinib combined with bortezomib and lenalidomide: A rationale for JAK/STAT pathway inhibition in myeloma patients. de Oliveira, MB., Fook-Alves, VL., Eugenio, AIP., et al.[2021]

The pan-HDAC inhibitor JNJ-26481585 effectively induces cell death in human multiple myeloma (MM) cells at low nanomolar concentrations, demonstrating its potential as a powerful anti-cancer agent.

In combination with other anti-myeloma treatments, JNJ-26481585 shows additive effects, suggesting it could enhance the efficacy of existing therapies for treating multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical anti-myeloma activity of the novel HDAC-inhibitor JNJ-26481585. Stühmer, T., Arts, J., Chatterjee, M., et al.[2017]

The p38 MAPK inhibitor VX-745 effectively reduces the secretion of interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF) from bone marrow stromal cells without harming their viability, indicating a potential therapeutic role in multiple myeloma.

VX-745 not only inhibits the proliferation of multiple myeloma cells but also counters drug resistance linked to cell adhesion in the bone marrow environment, highlighting p38 MAPK as a promising target for improving treatment outcomes in patients with multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting p38 MAPK inhibits multiple myeloma cell growth in the bone marrow milieu. Hideshima, T., Akiyama, M., Hayashi, T., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

New investigational drugs with single-agent activity in multiple myeloma. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Trends in the multiple myeloma treatment landscape and survival: a U.S. analysis using 2011-2019 oncology clinic electronic health record data. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Relapsed and refractory multiple myeloma: A systematic review and network meta-analysis of the efficacy of novel therapies. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

The immunotherapy era of myeloma: monoclonal antibodies, vaccines, and adoptive T-cell therapies. [2022]

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

A phase 1 study of ruxolitinib, steroids and lenalidomide for relapsed/refractory multiple myeloma patients. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Ixazomib maintenance therapy in newly diagnosed multiple myeloma: An integrated analysis of four phase I/II studies. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

FDA Drug Approval: Elotuzumab in Combination with Lenalidomide and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma. [2018]

10. Germany pubmed.ncbi.nlm.nih.gov

The anti-myeloma effects of the selective JAK1 inhibitor (INCB052793) alone and in combination in vitro and in vivo. [2019]

11. Ireland pubmed.ncbi.nlm.nih.gov

Anti-myeloma effects of ruxolitinib combined with bortezomib and lenalidomide: A rationale for JAK/STAT pathway inhibition in myeloma patients. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Preclinical anti-myeloma activity of the novel HDAC-inhibitor JNJ-26481585. [2017]

13. United States pubmed.ncbi.nlm.nih.gov

Targeting p38 MAPK inhibits multiple myeloma cell growth in the bone marrow milieu. [2021]