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Antineoplastic Agents

Azacitidine

Decitabine

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MBG453 + HMA (azacitidine, decitabine, or INQOVI (oral decitabine))

MBG453

Solution for subcutaneous injection or intravenous infusion

INQOVI (oral decitabine)

Main objective of this study is to describe and evaluate safety and efficacy of MBG453 (sabatolimab) in combination with FDA approved HMAs of investigator's choice (IV Decitabine or Azacitidine /SC Azacitidine /Oral Decitabine (cedazuridine combination (INQOVI))

This is a single-arm, non- randomized, open label, phase II multi-center study of intravenous MBG453 (sabatolimab) added to FDA approved Hypomethylating agents of investigator's choice (IV/SC/ Oral) in adult participants with intermediate, high or very high risk myelodysplastic syndrome (MDS) as per IPSS-R criteria.

There are three separate periods of this study:

1. Screening period (signing of written informed consent through Day 1);
2. Core phase for 12 months;
3. Extension phase for efficacy and/or survival status (up to 12 months after core phase)
4. Post treatment safety follow-up monitoring for adverse events (AEs) for 30 days following the last dose of azacitidine or decitabine or INQOVI (oral decitabine), or 150 days following the last dose of MBG453 (sabatolimab), whichever is later).

STIMULUS MDS-US : Sabatolimab Added to HMA in Higher Risk MDS

Single-arm, Open Label, Phase II Study of MBG453 (Sabatolimab) Added to FDA Approved Hypomethylating Agents of Investigator's Choice (IV/SC/Oral) for Patients With Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS) as Per IPSS-R Criteria (US Multi-center) (STIMULUS MDS-US)

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.

Adverse events will be assessed at each visit. Any clinically significant laboratory value or vital sign determined by the investigator to meet the definition of an adverse event will be reported.

Complete remission with MBG453 (sabatolimab) in combination with HMAs (IV/SC/Oral) in participants with intermediate, high, or very high risk MDS by 12 months

Defined as time from enrollment to disease progression (including transformation to leukemia per WHO 2016 classification), relapse from CR according to IWG-MDS or death due to any cause, whichever occurs first, as per investigator assessment by 12 months post LPFT

Time from enrollment to death due to any cause

Time from enrollment to \> 20% blasts in bone marrow/peripheral blood (per WHO 2016 classification) or death due to any cause

Percentage of complete response, marrow complete response, and/or partial response according to IWG-MDS response criteria as per investigator assessment

Time from the date of the first documented CR to the date of first documented relapse from CR or death due to any cause, whichever occurs first

Time from first treatment to the first documented complete remission

Transfusion independence is defined as less than 3 units of transfusion within any 8 consecutive weeks on study

Novartis Pharmaceuticals

Recurrence

Head and Neck Neoplasms

Durvalumab

Antineoplastic Agents, Immunological

Oral decitabine (ASTX 727) will be administered alone in Cycle 1 and the combination of oral decitabine and durvalumab therapy will be given in Cycles 2-12.

Oral Decitabine

Sara Pai, MD, PhD

This is a non-randomized, open-label, Phase IbI study to assess the safety and efficacy of oral decitabine (ASTX727) and durvalumab (MEDI4736) combination therapy in the treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) who have progressed during or after treatment with anti-PD-1, anti-PD-L1, or anti-CTLA-4 monotherapy for recurrent and/or metastatic disease. The clinical trial is studying drugs that can boost the participant's immune system against the cancer cells as a possible treatment for head and neck cancer.

The study interventions involved in this study are:

* Oral Decitabine (ASTX 727)
* Durvalumab (MEDI4736)

This research study is a Phase I clinical trial, which tests the safety of an investigational drug and also tries to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the drugs are still being studied.

The FDA (the U.S. Food and Drug Administration) has not approved durvalumab (MEDI4736) or tremelimumab as a treatment for any disease.

The FDA (the U.S. Food and Drug Administration) has not approved oral decitabine (ASTX 7272) for the participant's specific disease but it has been approved for other uses.

This is a first in human study evaluating the safety of combining these different drugs. Durvalumab (MEDI4736) is part of a family of proteins that make up the immune system. The body generates these proteins, or antibodies, in response to foreign substances (particles not typically found in the body such as bacteria and viruses) and these antibodies can protect against infection. Durvalumab (MEDI4736) is an antibody that is being studied in several other clinical trials to see if it has an effect in helping the immune system to recognize and eliminate abnormal cells in the body.

Investigators hope that decitabine may increase the chance of the immune system to recognize the cancer cells.

In this research study, the investigators are looking for the highest effective dose of decitabine in combination with durvalumab (MEDI4736) to improve the natural ability of the immune system to recognize and target head and neck cancer cells.

Oral Decitabine (ASTX727) and Durvalumab in Recurrent and/or Metastatic Head and Neck Cancer Patients

A Phase IB Rescue Study With Oral Decitabine (AStX727) and Durvalumab (MEDI4736) Combination Therapy in Recurrent and/or Metastatic Head and Neck Cancer Patients Who Have Progressed on Anti-PD-1, Anti-PD-L1, or Anti-CTLA-4 Monotherapy

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
STIMULUS MDS-US : Sabatolimab Added to HMA in Higher Risk MDS	NCT04878432	Myelodysplastic...	MBG453 Azacitidine Decitabine INQOVI (oral de...	18 Years - 99 Years	Novartis
Oral Decitabine (ASTX727) and Durvalumab in Recurrent and/or Metastatic Head and Neck Cancer Patients	NCT03019003	Head and Neck C...	Oral Decitabine Durvalumab	18 Years -	Massachusetts General Hospital

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