MT-601 for Lymphoma

(APOLLO Trial)

Recruiting at 7 trial locations

Overseen By Juan Vera, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Marker Therapeutics, Inc.

Must not be taking: Immunosuppressants, Corticosteroids, Chemotherapy, others

Disqualifiers: CNS pathology, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

79 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called MT-601 (also known as Neldaleucel) for individuals with lymphoma that has returned or isn't responding to standard treatments. The goal is to determine the safety and effectiveness of MT-601 by trying different doses. Individuals diagnosed with specific types of lymphoma who have tried at least two other treatments without success might be suitable candidates for this trial. As a Phase 1 trial, this research aims to understand how MT-601 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 protocol does not specify if you must stop taking your current medications. However, certain treatments like chemotherapy, monoclonal antibodies, and systemic immunosuppressants must be stopped within specific timeframes before participating. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that MT-601 is likely to be safe for humans?

Research has shown that MT-601 was safe in earlier studies with patients who have B cell lymphomas. These studies found no serious side effects related to the dose, indicating that patients generally tolerated the treatment well. Although this Phase 1 trial focuses primarily on safety, the current data is encouraging and suggests that MT-601 may be safe for use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for lymphoma, which often involve chemotherapy, radiation, or targeted therapies, MT-601 is unique because it harnesses a novel approach using a specified number of engineered cells. Researchers are excited about MT-601 because it targets lymphoma cells directly and precisely, potentially offering a more tailored and effective treatment option. Additionally, by adjusting the dose between 200 million and 400 million cells, MT-601 aims to optimize effectiveness and minimize side effects, which could lead to a more personalized and less invasive treatment experience for patients.

What evidence suggests that MT-601 might be an effective treatment for lymphoma?

Research has shown that MT-601, which participants in this trial will receive, may help treat relapsed or hard-to-treat lymphoma. In an earlier study, 66% of patients with Non-Hodgkin Lymphoma (NHL) experienced positive effects from this treatment. Reducing certain immune cells, a process called lymphodepletion, improved the response and effectiveness of MT-601. These early findings suggest that MT-601 could be a good option for those who haven't responded to other treatments. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with relapsed or refractory Non-Hodgkin Lymphoma who have a life expectancy of at least 12 weeks and are in relatively good health (Karnofsky/Lansky score ≥70). They must have their own cells available to create MT-601, meet blood, liver, and kidney function requirements, agree to birth control measures, and not be pregnant or breastfeeding. Those ineligible for CD19+ CAR T cell therapy may also join.

Inclusion Criteria

It's been over a week since my last cancer treatment.

I am using or willing to use effective birth control or practice abstinence.

I had partial success with CAR T cell therapy targeting CD19.

Exclusion Criteria

Pregnant or lactating patients

I have a severe infection that is causing significant symptoms.

I am currently taking corticosteroids not just for replacement.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of MT-601 to assess safety and tolerability

4-8 weeks

Multiple visits for dose administration and monitoring

Dose Expansion

Participants receive MT-601 at the determined safe dose to evaluate clinical efficacy

12 months

Regular visits for treatment and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• MT-601

Trial Overview The study tests the safety and effectiveness of MT-601 on patients with Non-Hodgkin Lymphoma that has returned or resisted treatment. It's a Phase 1 trial involving multiple centers where participants receive a flat dose of MT-601 made from their own cells to see how well it works against their lymphoma.

How Is the Trial Designed?

Group I: Single Arm Study Experimental Treatment 1 Intervention

Single arm study evaluating MT-601 investigational product at 200 million cells and 400 million cells per dose

Who Is Running the Clinical Trial?

Marker Therapeutics, Inc.

Lead Sponsor

Trials

8

Recruited

450+

Published Research Related to This Trial

In a phase II trial involving 217 patients with relapsed or refractory aggressive non-Hodgkin's lymphoma, lenalidomide demonstrated an overall response rate of 35%, with 13% achieving complete remission and 22% achieving partial remission.

Lenalidomide was found to be well tolerated, although myelosuppression was a common side effect, particularly with grade 4 neutropenia occurring in 17% of patients, indicating that while effective, monitoring for blood-related side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma. Witzig, TE., Vose, JM., Zinzani, PL., et al.[2022]

In the MCL-001 trial involving 134 patients with relapsed mantle-cell lymphoma, lenalidomide showed an overall response rate of 28%, with a median duration of response of 16.6 months, indicating its effectiveness in this heavily pretreated population.

Lenalidomide was found to have a predictable safety profile, with the most common severe side effects being neutropenia (43%) and thrombocytopenia (28%), suggesting that while it is effective, monitoring for these adverse events is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-agent lenalidomide in patients with mantle-cell lymphoma who relapsed or progressed after or were refractory to bortezomib: phase II MCL-001 (EMERGE) study. Goy, A., Sinha, R., Williams, ME., et al.[2021]

In a study of 32 patients with nasal NK/T-cell lymphoma, an intensive combined therapy led to a complete response in 65% of cases, demonstrating significant efficacy in treating this rare and aggressive cancer.

The treatment, which included high-dose chemotherapy and radiotherapy, resulted in a 100% event-free survival rate at 5 years for those who responded completely, indicating a promising therapeutic approach for improving outcomes in a disease with historically poor prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nasal NK/T-cell lymphoma with disseminated disease treated with aggressive combined therapy. Avilés, A., Neri, N., Fernández, R., et al.[2018]

All patients with nasal natural killer/T-cell lymphoma (NNKTL) showed expression of PD-L1 in their tumor samples, indicating a potential mechanism for immune evasion.

Higher levels of soluble PD-L1 (sPD-L1) in the blood were associated with worse prognosis, suggesting that sPD-L1 could serve as a prognostic marker and that targeting the PD-1/PD-L1 pathway may be a promising immunotherapy approach for NNKTL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed death-ligand 1 and its soluble form are highly expressed in nasal natural killer/T-cell lymphoma: a potential rationale for immunotherapy. Nagato, T., Ohkuri, T., Ohara, K., et al.[2022]

In a study of 121 high-risk diffuse large B-cell lymphoma (DLBCL) patients, higher pretreatment levels of soluble PD-1 (sPD-1) were associated with worse survival outcomes, indicating its potential as a prognostic marker.

sPD-1 levels decreased after three courses of immunochemotherapy, suggesting that monitoring sPD-1 could help assess treatment response and improve risk profiles for DLBCL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Soluble PD-1 but Not PD-L1 Levels Predict Poor Outcome in Patients with High-Risk Diffuse Large B-Cell Lymphoma. Vajavaara, H., Mortensen, JB., Leivonen, SK., et al.[2021]

In a study of 57 patients with relapsed/refractory mantle cell lymphoma (MCL), lenalidomide showed a 35% overall response rate, with a median duration of response lasting 16.3 months for those who responded.

The treatment was associated with manageable side effects, primarily neutropenia (46%), thrombocytopenia (30%), and anemia (13%), indicating that lenalidomide can be an effective option for patients with advanced MCL who have undergone multiple prior therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of lenalidomide in relapsed/refractory mantle cell lymphoma: subset analysis of the NHL-003 study. Zinzani, PL., Vose, JM., Czuczman, MS., et al.[2021]

Mantle cell lymphoma (MCL) has historically had poorer treatment outcomes compared to other non-Hodgkin's lymphoma subtypes, with many patients being ineligible for intensive therapies due to age and health conditions.

Current research is focusing on developing targeted therapies, such as the mTOR inhibitor temsirolimus and combination regimens with bortezomib, to improve treatment efficacy while minimizing side effects for patients with relapsed MCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status of targeted therapies for mantle cell lymphoma. Chang, JE., Kahl, BS.[2021]

In a case study of three patients with relapsed/refractory extranodal natural killer/T-cell lymphoma (ENKTL), a combination treatment of toripalimab (a PD-1 antibody), chidamide, etoposide, and thalidomide led to significant responses, with two patients achieving complete remission and one showing partial remission.

The treatment was associated with manageable side effects, primarily grade 2-3 leukocytopenia and anemia, suggesting that the PCET regimen could be a promising and tolerable option for improving outcomes in patients with R/R ENKTL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective Treatment with PD-1 Antibody, Chidamide, Etoposide, and Thalidomide (PCET) for Relapsed/Refractory Natural Killer/T-Cell Lymphoma: A Report of Three Cases. Du, L., Zhang, L., Li, L., et al.[2020]

Brexucabtagene autoleucel (KTE-X19) CAR T-cell therapy showed a remarkable 91% objective response rate and 68% complete response rate in 68 patients with relapsed/refractory mantle cell lymphoma after a median follow-up of 35.6 months, indicating its efficacy in this challenging patient population.

The therapy demonstrated durable long-term responses with manageable safety, as late-onset toxicities were infrequent, occurring in only 3% of patients, suggesting that KTE-X19 is a safe and effective treatment option even for those with high-risk characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-Year Follow-Up of KTE-X19 in Patients With Relapsed/Refractory Mantle Cell Lymphoma, Including High-Risk Subgroups, in the ZUMA-2 Study. Wang, M., Munoz, J., Goy, A., et al.[2023]

In a study of 107 patients with newly diagnosed extranodal NK/T-cell lymphoma (ENKTL), first-line treatment with anti-PD-1 antibody combined with asparaginase-based chemotherapy showed a higher overall response rate (86.11%) and complete remission rate (72.22%) compared to anti-PD-1 antibody alone (62.86% and 52.29%, respectively).

The pretreatment CD4/CD8 ratio greater than 0.83 was associated with better treatment response and longer progression-free survival (PFS), suggesting it could be a useful biomarker for predicting which patients will respond well to anti-PD-1 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line immunotherapy with anti-PD-1 antibody for extranodal NK/T-cell lymphoma: A retrospective study. Wang, X., Wen, L., Liao, J., et al.[2023]

Citations

1. ir.markertherapeutics.com ir.markertherapeutics.com/news-releases/news-release-details/marker-therapeutics-provides-update-phase-1-apollo-study

Press Releases Ongoing Phase 1 APOLLO study investigating MT-601 in patients with relapsed B cell lymphoma showed 66% of Non-Hodgkin Lymphoma (NHL) ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05798897

NCT05798897 | Safety and Preliminary Efficacy of MT-601 ... This study is a Phase 1, multicenter, open-label study designed to evaluate the safety and efficacy of MT-601 in participants with relapsed or refractory ...

3. firstwordpharma.com firstwordpharma.com/story/6515427

Marker Therapeutics Announces Upcoming Presentations ... Ongoing Phase 1 APOLLO study investigating MT-601 in patients with relapsed B cell lymphomas showed encouraging preliminary efficacy data.

4. onclive.com onclive.com/view/lymphodepletion-enhances-mar-t-cell-expansion-and-persistence-in-r-r-lymphoma

Lymphodepletion Enhances MAR T-Cell Expansion and ... Lymphodepletion was associated with enhanced MAR T-cell response and antitumor activity with MT-601 in patients with relapsed/refractory lymphoma.

5. sec.gov sec.gov/Archives/edgar/data/1094038/000110465925082783/tm2524197d1_ex99-1.htm

Marker Therapeutics Provides Update on Phase 1 APOLLO ... A total of 24 B-cell lymphoma patients have been treated with MT-601 across 7 U.S. clinical sites, including 15 patients with Non-Hodgkin Lymphoma (NHL) and 9 ...

6. ir.markertherapeutics.com ir.markertherapeutics.com/news-releases/news-release-details/marker-therapeutics-announces-upcoming-presentations-mt-601

Press Releases ... MT-601 in patients with relapsed B cell lymphomas showed encouraging preliminary efficacy data. MT-601 demonstrated robust safety profile with no dose ...

7. reporter.nih.gov reporter.nih.gov/search/WHuqaVPUHUyxNHbFsaLkrg/project-details/10922163

A Phase 1 Study of Patient-Derived Multi-Tumor ... - NIH RePORTER In a phase 1 trial of lymphoma patients using multiTAA-specific T cells targeting 5 TAAs, patients had durable responses for much longer than those typically ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05798897?term=NCT05798897&rank=1

Safety and Preliminary Efficacy of MT-601 in Patients With ... The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure.

9. nasdaq.com nasdaq.com/press-release/marker-therapeutics-announces-upcoming-presentations-mt-601-relapsed-non-hodgkin-and

Marker Therapeutics Announces Upcoming Presentations ... ... MT-601 in patients with relapsed B cell lymphomas showed encouraging preliminary efficacy data. MT-601 demonstrated robust safety profile ...