Talquetamab/Teclistamab + PD-1 Inhibitor for Multiple Myeloma

(TRIMM-3 Trial)

Recruiting at 29 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Janssen Research & Development, LLC

Must not be taking: PD-1 inhibitors

Disqualifiers: Plasma cell leukemia, Waldenstrom's, POEMS, others

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

Compensation: Varies

Number of Visits: Unknown

74 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the study is to identify the safe dose(s) of a PD-1 inhibitor in combination with talquetamab or teclistamab, and to characterize the safety and tolerability of talquetamab or teclistamab when administered in combination with a PD-1 inhibitor.

Will I have to stop taking my current medications?

The trial requires that you stop any prior antitumor therapy at least 21 days before starting the study treatment, with specific timeframes for certain therapies like proteasome inhibitors and immunomodulatory drugs. If you are on these types of medications, you will need to stop them before participating.

What data supports the effectiveness of the drug combination Talquetamab/Teclistamab + PD-1 Inhibitor for Multiple Myeloma?

Talquetamab and Teclistamab have both been approved for treating relapsed or refractory multiple myeloma, showing promise in patients who have tried multiple other treatments. While PD-1 inhibitors alone have not been very effective, combining them with other drugs has shown potential benefits, suggesting that this combination could be more effective. ^{1 2 3 4 5}

What safety data exists for PD-1 inhibitors in cancer treatment?

PD-1 inhibitors, used in various cancer treatments, generally have a manageable safety profile, making them suitable for outpatient use. However, they can cause side effects, including fever, increased liver enzyme levels, and rash, with some cases leading to severe reactions like pneumonitis (lung inflammation). ^{6 7 8 9 10}

What makes the Talquetamab/Teclistamab + PD-1 Inhibitor treatment unique for multiple myeloma?

This treatment is unique because it combines Talquetamab and Teclistamab, which are antibodies targeting specific proteins on cancer cells, with a PD-1 inhibitor that helps the immune system attack cancer cells more effectively. This combination approach is novel for multiple myeloma, as it leverages both direct targeting of cancer cells and enhancement of the immune response. ^{11 12 13 14 15}

Research Team

Janssen Research and Development, LLC Clinical Trial

Principal Investigator

Janssen Research and Development LLC

Eligibility Criteria

This trial is for individuals with relapsed or refractory multiple myeloma who have measurable disease and are not candidates for established therapies. They must be in good physical condition (ECOG score of 0 or 1) and haven't received certain treatments recently, including PD-1 inhibitors, stem cell transplants, or live vaccines.

Inclusion Criteria

My condition has returned or didn't respond to treatment, and I can't use standard therapies.

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

My cancer can be measured by blood or urine tests.

Exclusion Criteria

I have previously received PD-1 inhibitors or had a stem or organ transplant.

My multiple myeloma may be affecting my brain or spinal cord.

I haven't had cancer treatment in the last 3 weeks, including specific therapies in shorter time frames.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants will receive either talquetamab or teclistamab with a PD-1 inhibitor biweekly to identify safe dose levels

Up to 2 years 5 months

Dose Expansion

Participants will receive either treatment regimen A or treatment regimen B with a PD-1 inhibitor at the dose levels identified in Part 1

Up to 2 years 5 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• PD-1 Inhibitor
• Talquetamab
• Teclistamab

Trial Overview The study aims to determine safe doses when combining a PD-1 inhibitor with either talquetamab or teclistamab. It will also assess the safety and tolerability of these combinations in treating multiple myeloma.

Participant Groups

Group I: Part 2: Dose Expansion Experimental Treatment 3 Interventions

Participants will receive either treatment regimen A or treatment regimen B with a PD-1 inhibitor at the dose levels identified in Part 1.

Group II: Part 1: Dose Escalation Experimental Treatment 3 Interventions

Participants will receive either talquetamab (treatment regimen A) or teclistamab (treatment regimen B) with a PD-1 inhibitor biweekly.

Talquetamab is already approved in United States, European Union for the following indications:

Approved in United States as Talquetamab for:

• Relapsed or refractory multiple myeloma

Approved in European Union as Talquetamab for:

• Relapsed or refractory multiple myeloma

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

Teclistamab, a bispecific antibody targeting CD3 and BCMA, has received conditional approval in the EU and full approval in the US for treating adult patients with relapsed or refractory multiple myeloma after multiple prior therapies.

The approvals are based on its efficacy in patients who have undergone at least three to four previous treatments, including specific types of therapies, highlighting its role as a treatment option for difficult-to-treat cases of multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teclistamab: First Approval. Kang, C.[2022]

The introduction of new therapies, including proteasome inhibitors, immunomodulators, and various immunotherapies like CAR T-cell treatments, has significantly improved the five-year survival rate for multiple myeloma to nearly 60%.

Despite these advancements, multiple myeloma remains incurable, as patients often become resistant to treatments and experience relapses, highlighting the need for ongoing research and development of new therapeutic strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy of Multiple Myeloma: Current Status as Prologue to the Future. Abramson, HN.[2023]

Teclistamab-cqyv is an FDA and EMA-approved bispecific antibody that effectively targets multiple myeloma (MM) by engaging T cells to attack cancer cells, showing a 60% overall response rate in heavily pretreated relapsed/refractory patients.

This treatment is specifically designed for patients who have undergone at least three prior therapies and have shown disease progression, highlighting its role in advanced stages of MM where other treatments have failed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teclistamab-cqyv in multiple myeloma. Martino, EA., Bruzzese, A., Labanca, C., et al.[2023]

Talquetamab, a bispecific T-cell engager targeting GPRC5D and CD3, has received accelerated approval in the USA and conditional marketing authorization in the EU for treating adults with relapsed or refractory multiple myeloma, highlighting its potential as a new treatment option.

This approval marks a significant milestone in the development of talquetamab, indicating its efficacy and safety in addressing a challenging form of cancer that has not responded to previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talquetamab: First Approval. Keam, SJ.[2023]

Pembrolizumab, an anti-PD-1 antibody, has been approved for treating unresectable or metastatic melanoma, especially in patients who have progressed after ipilimumab treatment, marking a significant advancement in immuno-oncology.

The drug has also received breakthrough status for treating non-small cell lung cancer (NSCLC) that is EGFR mutation-negative and ALK rearrangement-negative, indicating its broad potential in cancer therapy, with ongoing trials to explore its use in various tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab. Khoja, L., Butler, MO., Kang, SP., et al.[2022]

Blocking the PD-1 pathway with specific drugs has shown clinical effectiveness in treating advanced cancers like melanoma and lung cancer, by enhancing the body's anti-tumor immune response.

These PD-1/PD-L1 blocking drugs have a manageable safety profile, making them suitable for outpatient treatment and potential use in combination therapies, with ongoing research focused on identifying biomarkers for better patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antagonists of PD-1 and PD-L1 in Cancer Treatment. Lipson, EJ., Forde, PM., Hammers, HJ., et al.[2022]

In a phase 3 study involving 582 patients with advanced nonsquamous non-small-cell lung cancer (NSCLC), nivolumab significantly improved overall survival compared to docetaxel, with a median survival of 12.2 months versus 9.4 months, respectively.

Nivolumab also had a much lower rate of severe treatment-related adverse events (10%) compared to docetaxel (54%), indicating a better safety profile while maintaining efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. Borghaei, H., Paz-Ares, L., Horn, L., et al.[2022]

The combination of vibostolimab and pembrolizumab is well tolerated by patients, indicating a favorable safety profile for this treatment regimen.

This combination therapy demonstrates antitumor activity, suggesting it may be an effective option for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Anti-TIGIT Antibody with a PD-1 Inhibitor Shows Promise in Solid Tumors. [2022]

Monoclonal antibodies like nivolumab and pembrolizumab have shown significant efficacy in treating non-small cell lung cancer (NSCLC), with some patients experiencing durable responses lasting years after treatment.

Despite the success of these therapies, many NSCLC patients do not respond to anti-PD-1/PD-L1 treatments, highlighting the urgent need for biomarkers to identify which patients are likely to benefit from these immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-L1 biomarker testing for non-small cell lung cancer: truth or fiction? Grigg, C., Rizvi, NA.[2022]

Atezolizumab combined with chemotherapy showed promising efficacy in treating advanced, treatment-naïve non-small-cell lung cancer (NSCLC), with overall response rates of 36% to 68% across different chemotherapy regimens in a study of 76 patients.

The treatment was generally well tolerated, although common severe side effects included neutropenia and anemia, indicating a manageable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival follow-up of atezolizumab in combination with platinum-based doublet chemotherapy in patients with advanced non-small-cell lung cancer. Liu, SV., Camidge, DR., Gettinger, SN., et al.[2022]

Nivolumab was the first immune checkpoint inhibitor approved for non-small cell lung cancer (NSCLC) by the FDA, showing a survival advantage over the traditional treatment docetaxel in recurrent squamous NSCLC, which is known to be challenging to treat.

Several other immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway are in late-stage development, with ongoing research into their efficacy and the potential use of PD-L1 expression as a biomarker to identify patients who are most likely to benefit from these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Perspectives in Immunotherapy for Non-Small Cell Lung Cancer. Garon, EB.[2020]

A phase I study found that the combination of utomilumab, an investigational antibody targeting CD137, and pembrolizumab is safe and well tolerated in patients with various solid cancers.

This combination therapy resulted in sustained responses, suggesting potential efficacy in treating these types of cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancing PD-1 Blockade in Solid Tumors. [2021]

References

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

Teclistamab: First Approval. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Immunotherapy of Multiple Myeloma: Current Status as Prologue to the Future. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Teclistamab-cqyv in multiple myeloma. [2023]

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

Talquetamab: First Approval. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Promises and Pitfalls in the Use of PD-1/PD-L1 Inhibitors in Multiple Myeloma. [2019]

6. Italy pubmed.ncbi.nlm.nih.gov

Efficacy and safety of PD-1/PD-L1 inhibitors plus chemotherapy for triple-negative breast cancer: a systematic review and meta-analysis. [2022]

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

Pembrolizumab. [2022]

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

Antagonists of PD-1 and PD-L1 in Cancer Treatment. [2022]

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

Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. [2022]

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

Dabrafenib, trametinib and pembrolizumab or placebo in BRAF-mutant melanoma. [2022]

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

An Anti-TIGIT Antibody with a PD-1 Inhibitor Shows Promise in Solid Tumors. [2022]

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

PD-L1 biomarker testing for non-small cell lung cancer: truth or fiction? [2022]

13. England pubmed.ncbi.nlm.nih.gov

Long-term survival follow-up of atezolizumab in combination with platinum-based doublet chemotherapy in patients with advanced non-small-cell lung cancer. [2022]

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

Current Perspectives in Immunotherapy for Non-Small Cell Lung Cancer. [2020]

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

Enhancing PD-1 Blockade in Solid Tumors. [2021]