Continued Sabatolimab Treatment for Cancer

Recruiting at 30 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

33 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is intended to collect safety data from participants who completed the parent protocols but are still benefiting from study treatment. The study population consists of participants who tolerate study treatment of the parent studies. Collecting safety information from long-term exposure might offer the unique opportunity to detect rare Adverse Events.

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.

What data supports the idea that Continued Sabatolimab Treatment for Cancer is an effective treatment?

The available research shows that Sabatolimab, when used with other treatments, has shown promise in treating certain types of cancer. For example, in a study involving patients with higher-risk myelodysplastic syndromes, Sabatolimab combined with another drug improved outcomes compared to a placebo. This suggests that Sabatolimab can be effective in enhancing the body's immune response to fight cancer. Additionally, it has been tested in combination with another antibody in patients with advanced solid tumors, indicating its potential in treating various cancer types. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Sabatolimab for cancer treatment?

Research shows that Sabatolimab, when used with other drugs like spartalizumab, can help treat advanced solid tumors by targeting specific proteins on cancer and immune cells. It has also shown promise in improving survival in patients with certain blood cancers by reactivating the immune system and directly attacking cancer cells. ^{1 2 3 4 5}

What safety data is available for sabatolimab treatment?

Sabatolimab has been evaluated in several clinical trials for its safety and efficacy. A Phase I/Ib trial assessed sabatolimab alone and in combination with spartalizumab in patients with advanced solid tumors, focusing on safety and efficacy. Additionally, a Phase 2 trial (STIMULUS-MDS1) investigated the safety of sabatolimab combined with hypomethylating agents in patients with higher-risk myelodysplastic syndromes. These studies provide initial safety data for sabatolimab in different cancer types. ^{1 2 3 4 6}

Is sabatolimab generally safe for humans?

Sabatolimab has been studied in clinical trials for various cancers, including advanced solid tumors and myelodysplastic syndromes. These studies evaluated its safety, often in combination with other treatments, and are part of ongoing research to ensure it is safe for human use. ^{1 2 3 4 6}

Is the drug Sabatolimab a promising treatment for cancer?

Yes, Sabatolimab is a promising drug for cancer treatment. It is an immunotherapy that targets the TIM-3 receptor, which is involved in regulating immune responses. By blocking this receptor, Sabatolimab can enhance the body's ability to fight cancer. It has shown potential in treating advanced solid tumors and blood-related cancers like acute myeloid leukemia and myelodysplastic syndromes. This drug works by boosting the immune system's attack on cancer cells, making it a valuable addition to cancer therapies. ^{1 2 3 4 7}

What makes the drug Sabatolimab unique for cancer treatment?

Sabatolimab is unique because it targets the TIM-3 receptor, which is found on both immune cells and cancer cells, allowing it to enhance the body's immune response against cancer in multiple ways. This includes blocking interactions that suppress the immune system and promoting the destruction of cancer cells, making it different from other treatments that typically target only one aspect of the immune response. ^{1 2 3 4 7}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

References

1. United States 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. [2023]

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

Characterization of sabatolimab, a novel immunotherapy with immuno-myeloid activity directed against TIM-3 receptor. [2023]

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

TIM-3: a tumor-associated antigen beyond checkpoint inhibition? [2023]

4. England 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. [2023]

5. England 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. [2023]

6. England 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☆. [2022]

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

Trial Watch: Immunostimulatory monoclonal antibodies in cancer therapy. [2021]