Myelodysplastic SyndromePhase 1NCT06616636
A Phase Ib Study of Rezatapopt in Combination With Azacitidine in Patients With TP53Y220C Mutant Myeloid Malignancies (Acute Myeloid Leukemia or Myelodysplastic Syndrome)
A Phase 1 study testing Azacitidine and Rezatapopt in people with Myelodysplastic Syndrome and Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 2 sites in United States.
Trial summary
A non-randomized phase Ib study of PC14586 (PMV therapeutics) in patients diagnosed with TP53Y220C-mutant myeloid malignancies, including AML and MDS. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndrome, Acute Myeloid Leukemia
- What is being tested?
- Azacitidine and Rezatapopt
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 2 sitesUnited States
- Study dates
- 30 Jan 2025to 27 Aug 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient is ≥ 18 years of age at the time of signing the informed consent form (ICF).
- Patient is willing and able to adhere to the study visit schedule and other protocol requirements.
- Patient has relapsed or primary refractory AML or MDS
- Any other comorbidity that per the investigator renders a patient inappropriate for intensive chemotherapy.
- Patients with MDS must be classified as MDS-IB1 or IB2 as per WHO 2022 criteria32
- TP53Y220C mutation confirmed by CLIA-approved local testing with a variant allele frequency \>2%.
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- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2
- Patient has adequate organ function defined as:
- Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 3 x ULN, unless considered due to leukemic organ involvement.
- Serum total bilirubin ≤ 1.5 x ULN. Higher levels are acceptable if these can be attributed to ineffective erythropoiesis, leukemia organ involvement or Gilbert\'s syndrome.
- Serum creatinine \< 2 x ULN or creatinine clearance \> 40 mL/min based on validated glomerular filtration rate (GFR) estimation (Cockcroft-Gault, CKD-epi, or MDRD equations).
- Females of childbearing potential may participate provided they have a negative serum or urine pregnancy test at screening and a negative serum OR urine pregnancy test within 72 hours of starting on treatment. They also must agree to either abstain from sexual intercourse or use two forms of a highly effective method of contraception while on study and up to 3 months after the last dose of the study drug.
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) 14 days prior to study entry and for the duration of study participation. This includes all female patients between the onset of menses and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following:
- Postmenopausal (no menses in greater than or equal to 12 consecutive months). History of hysterectomy or bilateral salpingo-oophorectomy. Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).
- History of bilateral tubal ligation or another surgical sterilization procedure.
- Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
- Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after completion of investigational agent administration.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Patient has received prior chemotherapy, targeted therapy, immunotherapy, or treatment with an investigational anticancer agent within 14 days or 5 half-lives (if half-life is known), whichever is shorter, before receiving their first dose of study drug.
- Patient has received radiotherapy within 14 days.
- Patients with acute promyelocytic leukemia
- Subject has immediate life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation.
- Patients with active, uncontrolled leukemia involvement of the CNS
- Subject has known active viral infection with human immunodeficiency virus (HIV), or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
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- Subject is known to have dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally.
- Subject has active uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment).
- Patient has any unresolved toxicities from prior anti-cancer therapy greater than Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2 prior chemotherapy induced neuropathy.
- Patient has had major surgery within 2 weeks prior to the planned start of study treatment.
- Female subject who is pregnant or lactating.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to azacitidine, rezetapopt or other agents used in study.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Courtney DiNardo, MD, 713-794-1141, cdinardo@mdanderson.org
Courtney DiNardo, MD
- Recruiting
Moffitt Cancer Center
Tampa, Florida, 33612
David Sallman, MD, 813-745-5639, David.sallman@moffitt.org
David Sallman, MD
About this study
A non-randomized phase Ib study of PC14586 (PMV therapeutics) in patients diagnosed with TP53Y220C-mutant myeloid malignancies, including AML and MDS.
Read the detailed description
Primary Objective:
To assess the safety and tolerability of rezatapopt in TP53Y220C -mutant myeloid malignancies (AML, MDS)
Secondary Objectives:
- To determine the clinical efficacy of rezatapopt in R/R and newly diagnosed patients with TP53Y220C -mutant myeloid malignancies
- To assess event free survival (EFS) and overall survival (OS) in patients receiving rezatapopt in combination with AZA +/- VEN
- To assess duration of response in patients receiving rezatapopt in combination with AZA
- Characterize the pharmacokinetics of rezatapopt in combination with AZA
Exploratory Objectives:
- To assess changes in the variant allele frequencies of TP53Y220C mutations via next-generation sequencing.
- To describe mutational profiles of patients on study at screening, response and at relapse and correlate to clinical parameters.
- To assess changes in clonal architecture based on bone marrow aspirate samples using single cell sequencing.
- To evaluate for p53 activation and changes in the immunologic profile of patients of TP53Y220C mutations.
- Conditions
- Myelodysplastic Syndrome, Acute Myeloid Leukemia
- Being tested
- Azacitidine, Rezatapopt
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzacitidineDrug
Given by IV
RezatapoptDrug
Given orally with food
| Study group | Role | What they receive |
|---|---|---|
| Rezatapopt + Azacitidine | Experimental | Participants will receive treatment on an inpatient or outpatient basis. Every cycle participants will take rezatapopt daily and receive azacitidine by IV for 7 days. Receives: Drug: Azacitidine; Drug: Rezatapopt |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and adverse events (AEs)
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Measured: Through study completion; an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2024
- Study start30 Jan 2025
- Primary completion27 Aug 2027 (estimated)
- Study completion27 Aug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myelodysplastic SyndromeStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Memorial Sloan Kettering Cancer Center, PMV Pharmaceuticals, Inc
- Responsible party
- Sponsor
- Investigators
- Courtney DiNardo, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06616636
- Sponsor's protocol ID
- 2024-0371
- Other IDs
- NCI-2024-08191
- Status last verified
- Oct 2026
- First submitted
- 25 Sep 2024
- Last updated
- 9 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Carter BZ, Mak PY, Ayoub E, Wu X, Ke B, Nishida Y, Futreal A, Ostermann LB, Bedoy AD, Boettcher S, DiNardo CD, Puzio-Kuter A, Poyurovsky MV, Levine A, Andreeff M. Restoring p53 wild-type conformation in TP53-Y220C-mutant acute myeloid leukemia. Blood. 2025 Nov 20;146(21):2574-2588. doi: 10.1182/blood.2025028935.
PubMed 40608889
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib Study of Rezatapopt in Combination With Azacitidine in Patients With TP53Y220C Mutant Myeloid Malignancies (Acute Myeloid Leukemia or Myelodysplastic Syndrome)
- ClinicalTrials.gov ID
- NCT06616636
- Acronym / sponsor ID
- 2024-0371
- Conditions
- Myelodysplastic Syndrome, Acute Myeloid Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Memorial Sloan Kettering Cancer Center, PMV Pharmaceuticals, Inc
- Study start
- 30 Jan 2025 (actual)
- Primary completion
- 27 Aug 2027 (estimated)
- Study completion
- 27 Aug 2029 (estimated)
- First posted
- 27 Sep 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A non-randomized phase Ib study of PC14586 (PMV therapeutics) in patients diagnosed with TP53Y220C-mutant myeloid malignancies, including AML and MDS.
Detailed description
Primary Objective:
To assess the safety and tolerability of rezatapopt in TP53Y220C -mutant myeloid malignancies (AML, MDS)
Secondary Objectives:
- To determine the clinical efficacy of rezatapopt in R/R and newly diagnosed patients with TP53Y220C -mutant myeloid malignancies
- To assess event free survival (EFS) and overall survival (OS) in patients receiving rezatapopt in combination with AZA +/- VEN
- To assess duration of response in patients receiving rezatapopt in combination with AZA
- Characterize the pharmacokinetics of rezatapopt in combination with AZA
Exploratory Objectives:
- To assess changes in the variant allele frequencies of TP53Y220C mutations via next-generation sequencing.
- To describe mutational profiles of patients on study at screening, response and at relapse and correlate to clinical parameters.
- To assess changes in clonal architecture based on bone marrow aspirate samples using single cell sequencing.
- To evaluate for p53 activation and changes in the immunologic profile of patients of TP53Y220C mutations.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Rezatapopt + Azacitidine | Experimental | Drug: Azacitidine, Drug: RezatapoptParticipants will receive treatment on an inpatient or outpatient basis. Every cycle participants will take rezatapopt daily and receive azacitidine by IV for 7 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Patient is ≥ 18 years of age at the time of signing the informed consent form (ICF).
- Patient is willing and able to adhere to the study visit schedule and other protocol requirements.
- Patient has relapsed or primary refractory AML or MDS
- Any other comorbidity that per the investigator renders a patient inappropriate for intensive chemotherapy.
- Patients with MDS must be classified as MDS-IB1 or IB2 as per WHO 2022 criteria32
Key exclusion criteria (12 listed)
- Patient has received prior chemotherapy, targeted therapy, immunotherapy, or treatment with an investigational anticancer agent within 14 days or 5 half-lives (if half-life is known), whichever is shorter, before receiving their first dose of study drug.
- Patient has received radiotherapy within 14 days.
- Patients with acute promyelocytic leukemia
- Subject has immediate life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation.
- Patients with active, uncontrolled leukemia involvement of the CNS
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AzacitidineGiven by IV | Drug | Rezatapopt + Azacitidine |
| RezatapoptGiven orally with food | Drug | Rezatapopt + Azacitidine |
Primary outcome
Safety and adverse events (AEs)
Time frame: Through study completion; an average of 1 year
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2026.
- Derived from this study: PubMed 40608889Carter BZ, Mak PY, Ayoub E, Wu X, Ke B, Nishida Y, Futreal A, Ostermann LB, Bedoy AD, Boettcher S, DiNardo CD, Puzio-Kuter A, Poyurovsky MV, Levine A, Andreeff M. Restoring p53 wild-type conformation in TP53-Y220C-mutant acute myeloid leukemia. Blood. 2025 Nov 20;146(21):2574-2588. doi: 10.1182/blood.2025028935.
- MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Courtney DiNardo, MD principal investigator
M.D. Anderson Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Azacitidine and Rezatapopt in people with Myelodysplastic Syndrome and Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Courtney DiNardo, MD ((713) 794-1141, cdinardo@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and adverse events (AEs) (time frame: Through study completion; an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06616636, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2026.