Talquetamab/Teclistamab + PD-1 Inhibitor for Multiple Myeloma

(TRIMM-3 Trial)

Not currently recruiting at 32 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and tolerability of two experimental treatments, talquetamab and teclistamab, combined with a PD-1 inhibitor (a type of immunotherapy) for people with multiple myeloma. Multiple myeloma is a cancer affecting plasma cells in the bone marrow, and the study aims to find the right dose of the combination treatments. The trial includes two parts: one to determine the safe dose and another to test these doses in more participants. It seeks individuals diagnosed with multiple myeloma who have tried other treatments without success. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

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

Previous studies have shown that talquetamab has a safety profile similar to other drugs, with common side effects such as anemia (low red blood cell count) and neutropenia (low white blood cell count). Medical care can manage these side effects. One study involving 339 patients with relapsed or refractory multiple myeloma found that talquetamab was generally well-tolerated.

Teclistamab has also undergone safety testing. In a study with 342 patients, it was generally safe, with most side effects being mild to moderate. Both talquetamab and teclistamab have been studied in patients who have already tried other treatments and continue to be promising options for multiple myeloma.

The current trial, in its early phase, primarily aims to find a safe dose. While some evidence of safety exists, more research is needed to fully understand the risks involved. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about talquetamab and teclistamab for multiple myeloma because these treatments offer a novel approach compared to traditional options like chemotherapy and immunomodulatory drugs. Unlike most treatments that target cancer cells broadly, talquetamab and teclistamab are bispecific antibodies that specifically target BCMA (B-cell maturation antigen), a protein commonly found on multiple myeloma cells, and engage the immune system directly. This targeted mechanism could lead to more efficient cancer cell destruction with potentially fewer side effects. Additionally, combining these with a PD-1 inhibitor may enhance the immune response, offering a promising new strategy for patients who have exhausted other treatments.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

Research has shown that both talquetamab and teclistamab hold promise in treating multiple myeloma, a type of blood cancer. In this trial, participants will receive either talquetamab or teclistamab, each combined with a PD-1 inhibitor. Talquetamab has demonstrated a high success rate, with 72.6% of patients responding well to treatment for at least 9 months, and 69.9% of patients not experiencing disease progression for at least 6 months. Similarly, teclistamab has proven effective, with 65% of patients showing noticeable improvement. These treatments are considered safe and work well even for patients who have tried other treatments. This evidence suggests that both options could effectively manage multiple myeloma. ^{1 3 6 7 8}

Who Is on the Research Team?

Janssen Research and Development, LLC Clinical Trial

Principal Investigator

Janssen Research and Development LLC

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. onclive.com onclive.com/view/talquetamab-cetrelimab-leads-to-deep-durable-responses-in-r-r-multiple-myeloma

Talquetamab/Cetrelimab Leads to Deep, Durable ... The 9-month duration of response (DOR) and 6-month progression-free survival (PFS) rates were 72.6% and 69.9%, respectively. “These data support ...

2. thelancet.com thelancet.com/journals/lanhae/article/PIIS2352-3026(24)00385-5/fulltext

Safety and activity of talquetamab in patients with relapsed ... Talquetamab continued to demonstrate high overall response rates in heavily pretreated patients with relapsed or refractory multiple myeloma ...

3. ascpt.onlinelibrary.wiley.com ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt.70004

Recommended Phase II Doses of Talquetamab in Patients ... In the phase I/II MonumenTAL-1 study, overall response rates (ORRs) were > 66% in patients with RRMM treated with subcutaneous talquetamab at ...

4. jnjmedicalconnect.com jnjmedicalconnect.com/products/talvey/medical-content/clinical-outcomes-of-subsequent-therapies-following-talvey

Clinical Outcomes of Subsequent Therapies Following ... At a median follow-up of 9.5 months (range, 6-24), overall response rate (ORR) was 60% and median progression free survival (PFS) was 5.5 months ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11798766/

Talquetamab in Multiple Myeloma: Efficacy, Safety, and Future ... Administered following a step‐up dosing phase to manage cytokine release syndrome (CRS), talquetamab demonstrated a high overall response rate ( ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2023/761342Orig1s000MultidisciplineR.pdf

761342Orig1s000 - accessdata.fda.gov The primary safety data for talquetamab in this application focus on the RP2D cohorts, which ... or refractory multiple myeloma (RRMM) who received IV talquetamab ...

7. ema.europa.eu ema.europa.eu/en/documents/product-information/talvey-epar-product-information_en.pdf

Talvey, INN-talquetamab - European Medicines Agency The safety of TALVEY was evaluated in 339 adult patients with relapsed or refractory multiple myeloma, including patients treated with TALVEY at the recommended ...

8. jnjmedicalconnect.com jnjmedicalconnect.com/products/talvey/medical-content/talvey-occurrence-and-management-of-infections-and-hypogammaglobulinemia

TALVEY - Occurrence and Management of Infections ... An ongoing, open-label, phase 1/2 study evaluating the efficacy and safety of TALVEY in patients with relapsed or refractory multiple myeloma (RRMM)