Continued Sabatolimab Treatment for Cancer

Not currently recruiting at 41 trial locations

Overseen By Novartis Pharmaceuticals

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Novartis Pharmaceuticals

Must be taking: Sabatolimab

Disqualifiers: Pregnancy, Nursing, Unresolved toxicities, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety of long-term use of sabatolimab, a cancer treatment, by collecting data from participants who continue to benefit from it. The study tests different combinations of sabatolimab with other medications to identify the best approach. It suits individuals who participated in a previous sabatolimab trial, continue to benefit, and have adhered to the treatment plan. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

The protocol does not specify whether you need to stop taking your current medications. However, since this trial is for participants already on sabatolimab, it seems likely that you can continue your current medications unless otherwise advised by the study team.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It seems focused on participants already taking sabatolimab, so you may continue with it if you are benefiting from the treatment.

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

A previous study tested sabatolimab alone and with other drugs like spartalizumab in patients with advanced solid tumors. The results showed that sabatolimab was generally well-tolerated, with most people not experiencing severe side effects. Common mild side effects included tiredness and changes in blood cell counts.

For the combination of sabatolimab and azacitidine, studies have shown that the safety profile was similar to azacitidine alone, which is already used for certain blood conditions. This suggests that adding sabatolimab does not significantly increase side effects.

When combined with decitabine, sabatolimab showed safety results similar to using decitabine alone, indicating a comparable level of safety for patients.

In treatments combining sabatolimab with venetoclax and azacitidine, early studies aimed to ensure no severe toxicities occurred. These studies found the combination manageable for patients, with side effects in line with those expected from the individual drugs.

Overall, research suggests sabatolimab and its combinations are generally safe and well-tolerated, with side effects similar to those of the individual drugs commonly used in cancer care. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because sabatolimab offers a novel way to tackle cancer. Unlike traditional chemotherapy, which attacks rapidly dividing cells, sabatolimab targets TIM-3, a protein on immune cells that can suppress the immune response against cancer. By inhibiting TIM-3, sabatolimab aims to boost the body's natural ability to fight cancer. Additionally, combining sabatolimab with other agents like azacitidine, decitabine, spartalizumab, and venetoclax may enhance its effectiveness by attacking cancer on multiple fronts, offering new hope for improved outcomes.

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

Research shows that sabatolimab alone hasn't been very effective for cancer patients. In this trial, participants may receive sabatolimab combined with other treatments. When paired with azacitidine, sabatolimab has shown promising results, especially for patients with more serious forms of myelodysplastic syndromes, a type of blood disorder. Studies indicate that using sabatolimab with drugs like azacitidine or decitabine can lead to lasting positive effects, particularly in high-risk cases. Another treatment arm in this trial combines sabatolimab with spartalizumab and decitabine, which has shown some improvement in patients with solid tumors. Additionally, the combination of sabatolimab with venetoclax and azacitidine is under study in this trial and is known to improve outcomes in certain blood cancers. ^{1 2 3 4 6}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for patients with Chronic Myelomonocytic Leukemia or Myelodysplastic Syndrome who have completed a prior Novartis-sponsored study and are still benefiting from Sabatolimab. They must be compliant with the previous study's protocol, not pregnant, willing to follow contraception guidelines, and without unresolved toxicities from Sabatolimab.

Inclusion Criteria

I am currently in a Novartis study for sabatolimab and meet all its requirements.

Participant is currently benefiting from the treatment with sabatolimab as determined by guidelines of the parent protocol and investigator's judgment

Written informed consent obtained prior to enrolling in the roll-over study

Exclusion Criteria

I was taken off sabatolimab in a previous study due to side effects or other reasons.

I am unwilling or unable to follow the study's birth control requirements.

I had side effects from sabatolimab that stopped my treatment, but they're resolved now.

Timeline for a Trial Participant

Eligibility Evaluation

Participants are evaluated for eligibility to transition from the parent protocol to the roll-over protocol

Not specified

Treatment

Participants continue treatment with sabatolimab and combination agents as applicable, according to the schedule in the parent study

5 years

Continuous monitoring at each visit

Safety Monitoring

Adverse events (AEs) and serious adverse events (SAEs) are collected continuously throughout the study

5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Not specified

What Are the Treatments Tested in This Trial?

Interventions

• Sabatolimab
• Spartalizumab

Trial Overview The trial continues treatment with drugs like decitabine, Spartalizumab, Sabatolimab, Azacitidine, Venetoclax, and oral decitabine (INQOVI) for those previously responding well. It aims to collect long-term safety data on these treatments to identify any rare adverse events.

How Is the Trial Designed?

Group I: sabatolimab + venetoclax + azacitidine Experimental Treatment 3 Interventions

Patients will take sabatolimab 200 mg i.v./q2w and venetoclax 400 mg p.o. d1-14/q4wk and azacitidine 75 mg/m2/d d1-7/q4w.

Group II: sabatolimab + spartalizumab + decitabine Experimental Treatment 3 Interventions

Patients will take sabatolimab 400 mg i.v./q2w and decitabine 20 mg/m2/d d1-5 i.v. and spartalizumab 100 mg i.v/q2w.

Group III: sabatolimab + decitabine Experimental Treatment 2 Interventions

Patients will take Sabatolimab 400 mg i.v/q2w and decitabine 20 mg/m2/d d1-5 i.v.

Group IV: sabatolimab + azacitidine Experimental Treatment 2 Interventions

Patients will take sabatolimab 800 mg i.v and azacitidine 75 mg/m2/d d1-7 s.c. or i.v./q4w or sabatolimab 400 mg i.v/q2w and azacitidine 75 mg/m2/d d1-7 s.c. or i.v./q4w.

Group V: sabatolimab + HMA Experimental Treatment 2 Interventions

Patients will take sabatolimab 800 mg and azacitidine 75 mg/m2/d d1-7 or decitabine 20 mg/m2/d d1-5/ all q4w HMA means hypomethylating agents. Hypomethylating agents are azacitidine and decitabine.

Group VI: sabatolimab Experimental Treatment 1 Intervention

Patients will take sabatolimab 800 mg i.v q4w.

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

Sabatolimab is a novel immunotherapy targeting TIM-3, designed to reactivate the immune system and directly attack TIM-3+ leukemic cells, which could improve outcomes for patients with higher-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML).

The phase III STIMULUS-MDS2 trial is investigating the combination of sabatolimab and azacitidine to assess its effectiveness in enhancing survival rates for patients who are unfit for hematopoietic stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

STIMULUS-MDS2 design and rationale: a phase III trial with the anti-TIM-3 sabatolimab (MBG453) + azacitidine in higher risk MDS and CMML-2. Zeidan, AM., Giagounidis, A., Sekeres, MA., et al.[2023]

Sabatolimab, a humanized anti-TIM-3 monoclonal antibody, is being developed for treating myeloproliferative disorders like acute myeloid leukemia, showcasing its potential as a novel immunotherapy.

This therapy works through multiple mechanisms, including blocking TIM-3 and its ligands, modulating leukemic cell self-renewal, and promoting antibody-dependent phagocytosis of TIM-3-expressing leukemic cells, which may enhance the overall antitumor immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TIM-3: a tumor-associated antigen beyond checkpoint inhibition? Barth, S., Naran, K.[2023]

In a phase 2 trial involving 127 patients with higher-risk myelodysplastic syndromes, the addition of sabatolimab to hypomethylating agents did not significantly improve complete response rates or progression-free survival compared to placebo.

Despite the lack of significant efficacy, sabatolimab was generally well-tolerated, with manageable safety profiles, although there was one treatment-related death due to pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sabatolimab plus hypomethylating agents in previously untreated patients with higher-risk myelodysplastic syndromes (STIMULUS-MDS1): a randomised, double-blind, placebo-controlled, phase 2 trial. Zeidan, AM., Ando, K., Rauzy, O., et al.[2023]

In a phase I/II study involving 219 patients with advanced solid tumors, the combination of sabatolimab and spartalizumab was well tolerated, with fatigue being the most common treatment-related side effect.

While no responses were observed with sabatolimab alone, the combination treatment showed preliminary antitumor activity, with 5 patients achieving partial responses in various cancers, suggesting potential efficacy in specific populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/Ib Clinical Trial of Sabatolimab, an Anti-TIM-3 Antibody, Alone and in Combination with Spartalizumab, an Anti-PD-1 Antibody, in Advanced Solid Tumors. Curigliano, G., Gelderblom, H., Mach, N., et al.[2023]

In a phase 1 study involving 115 patients with advanced solid tumors, the combination of vibostolimab and pembrolizumab was well tolerated, with no dose-limiting toxicities reported and manageable treatment-related adverse events (TRAEs) occurring in 62% of patients receiving the combination therapy.

The combination therapy showed a confirmed objective response rate (ORR) of 26% in anti-PD-1/PD-L1-naive non-small-cell lung cancer (NSCLC) patients, indicating potential antitumor activity, while monotherapy had a low ORR of 0-3% in both naive and refractory NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-human phase 1 study of the anti-TIGIT antibody vibostolimab as monotherapy or with pembrolizumab for advanced solid tumors, including non-small-cell lung cancer☆. Niu, J., Maurice-Dror, C., Lee, DH., et al.[2022]

Immunostimulatory monoclonal antibodies (mAbs) like ipilimumab and nivolumab work by activating the immune system to fight cancer, specifically by targeting receptors that inhibit immune responses, such as CTLA4 and PD-1.

Ipilimumab has been FDA-approved for treating advanced melanoma, and ongoing clinical trials are exploring the efficacy and safety of other mAbs targeting CTLA4, PD-1, and co-stimulatory receptors like OX40 and GITR in various solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trial Watch: Immunostimulatory monoclonal antibodies in cancer therapy. Aranda, F., Vacchelli, E., Eggermont, A., et al.[2021]

Sabatolimab, a humanized monoclonal antibody targeting TIM-3, enhances T-cell killing and boosts inflammatory cytokine production by dendritic cells, indicating its potential to improve immune responses against cancer.

The antibody also facilitates the phagocytosis of TIM-3-expressing target cells and blocks TIM-3 interactions with its ligands, suggesting it has both direct anti-leukemic effects and immune-modulating properties, making it a promising candidate for treating myeloid cell neoplasms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of sabatolimab, a novel immunotherapy with immuno-myeloid activity directed against TIM-3 receptor. Schwartz, S., Patel, N., Longmire, T., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33883177/

Phase I/Ib Clinical Trial of Sabatolimab, an Anti-TIM ... - PubMed This phase I/II study evaluated the safety and efficacy of sabatolimab, with or without spartalizumab, in patients with advanced solid tumors.

2. aacrjournals.org aacrjournals.org/clincancerres/article/27/13/3620/671520/Phase-I-Ib-Clinical-Trial-of-Sabatolimab-an-Anti

Phase I/Ib Clinical Trial of Sabatolimab, an Anti–TIM-3 ... Median follow-up for efficacy was 5.7 months (0.2–39.6 months). Per RECIST v1.1, no responses were observed in patients receiving single-agent sabatolimab; SD ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37994196/

Phase Ib study of sabatolimab (MBG453), a novel ... Sabatolimab + HMA had a safety profile similar to that reported for HMA alone and demonstrated durable clinical responses in patients with HR/vHR-MDS. These ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02608268

NCT02608268 | Phase I-Ib/II Study of MBG453 as Single ... The purpose of this first-in-human study of MBG453 was to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumor activity ...

5. aacrjournals.org aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-20-4746/672142/am/Phase-I-Ib-clinical-trial-of-Sabatolimab-an-Anti

Phase I/Ib clinical trial of Sabatolimab, an Anti-TIM-3 Antibody ... No responses were seen with sabatolimab. Five patients receiving combination treatment had partial responses (6%; lasting 12-27 months), in colorectal cancer (n ...

6. ascpt.onlinelibrary.wiley.com ascpt.onlinelibrary.wiley.com/doi/10.1002/psp4.12962

Sabatolimab (MBG453) model‐informed drug development for ... Sabatolimab binding to TIM-3 on immune cells may reactivate the immune system, boosting its ability to eliminate LSCs and blasts. Sabatolimab ...