IRB Study Number 24-187
Status Recruiting
Institute Taussig Cancer Institute
Description
Primary Objectives
Evaluate the safety and tolerability of SGR-2921 as monotherapy
Identify the recommended Phase 2 dose (RP2D) including estimation of the maximum-tolerated dose (MTD)
Secondary Objectives
Evaluate the pharmacokinetics (PK) of SGR-2921
Investigate SGR-2921 preliminary antitumor activity
Inclusion Criteria
Subject must be 18 years of age or older at the time of signing the informed consent form (ICF).
Subject must understand and sign an ICF prior to any study-related assessments or procedures being conducted.
Subject must be able and willing to comply with the study protocol and adhere to the study visit schedule.
Subject must have an expected life expectancy ≥8 weeks.
Subject must have the ability to swallow and retain oral medication.
Subjects with a histologically confirmed diagnosis of either:
a. Relapsed or refractory (r/r) AML, defined as subjects who have relapsed after transplantation; subjects in second or later relapse; subjects who are refractory to initial induction or reinduction treatment; subjects who relapse after initial treatment; or subjects who are otherwise considered relapsed or refractory in the opinion of the Investigator
i. Subjects with prior autologous or allogeneic stem cell transplant are eligible but should have no clear evidence of Graft Versus Host Disease requiring treatment
ii. Subjects with AML must have failed treatment with available therapies known to be active or refused standard therapy
iii. Hydroxyurea is not considered a prior treatment regimen
b. High risk (HR) and very high risk (VHR) MDS per IPSS-R (Greenberg 2012) and/or IPSS-M (Bernard E, et al 2022). Note: online calculator can be found at https://mds-risk-model.com/
i. Subjects with HR and VHR MDS must have previously failed treatment with at least 4 cycles of a hypomethylating agent (HMA), or other available standard therapy.
ii. Hydroxyurea is not considered a prior treatment regimen.
Subject must be willing to allow bone marrow and peripheral blood sample collection for confirmation of diagnosis and exploratory analyses according to the SoA.
Subject must have Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤2 (See Appendix 2 for more details).
Subjects must have the following liver, and renal function laboratory values:
• ALT and AST ≤2.5 × ULN or ≤5.0 × ULN for subjects diagnosed with Gilbert’s syndrome.
• Serum total bilirubin ≤1.5 × ULN, or ≤2.5 × ULN for subjects diagnosed with Gilbert’s syndrome.
• Calculated creatinine clearance glomerular filtration rate (GFR) ≥60mL/min, based on Cockcroft-Gault formula, or local equivalent method.
Subjects with a known history of hepatitis B virus (HBV) infection must have a negative serologic or polymerase chain reaction (PCR) test result for HBV. Subjects with active HBV disease must be on suppressive antiviral therapy prior to initiation of study drug.
Subjects with a known history of hepatitis C virus (HCV) must have a negative test result for HCV antibody or HCV RNA. Subjects with a history of HCV infection may be enrolled if the subject has completed curative antiviral treatment and has an HCV load below the limit of quantification.
Subjects with known human immunodeficiency virus (HIV) that can be enrolled if the CD4+ T-cell (CD4+) counts are >350 cells/μL and are on active treatment for HIV and have no evidence of active viral infection, by PCR testing.
Subjects must refrain from gamete donation from the first dose of SGR-2921, throughout the study, and for 3 months after treatment discontinuation.
Males and females of childbearing potential (FCBP)† must agree to utilize a highly effective method of contraception‡ for the duration of the study and up to 90 days after administration of the last dose of study treatment.
Females of childbearing potential must have a negative serum pregnancy test within 14 days of the first dose of study treatment (during screening), a negative serum or urine pregnancy test within 72 hours prior to the first dose of study treatment, and must agree to ongoing pregnancy testing throughout the study and up to 90 days after administration of the last dose of study treatment. A FCBP must also agree to utilize a highly effective method of contraception‡ for the duration of the study and up to 90 days after administration of the last dose of study treatment. The following methods of contraception are permitted during the study:
• Combined estrogen and progestogen hormonal contraception associated with inhibition of ovulation
− oral
− intravaginal
− transdermal
• Progestogen-only hormonal contraception associated with inhibition of ovulation:
− oral
− injectable
− implantable
• Intrauterine device (IUD)
• Intrauterine hormone-releasing system (IUS)
• Bilateral tubal occlusion
• Male partner who has undergone a vasectomy or vas-occlusive contraception at least 90 days prior to screening
• Female prophylactic sheath (i.e., condom)
• Occlusive cap with spermicidal foam, gel, cream, or suppository
Male subjects must agree to utilize a highly effective method of contraception‡ for the duration of the study and up to 90 days after administration of the last dose of study treatment. The following methods of contraception are permitted for male subjects during the study:
• Vasectomy or vas-occlusive contraception at least 90 days prior to screening
• Prophylactic sheath (i.e., condom) with or without spermicidal foam or gel
Both male and female subjects may commit to true abstinence¶ in place of the contraception forms listed above.
Exclusion Criteria
Subjects with active malignancies within two years prior to the first dose, or requiring ongoing treatment, not related to AML or MDS, with the exception of non-invasive basal cell or squamous cell carcinoma, or in situ tumors with low likelihood of becoming invasive or metastasizing, or other local tumors considered cured.
Subjects with clinical evidence of central nervous system (CNS) or pulmonary leukostasis, ≥ Grade 3 disseminated intravascular coagulation, or active CNS leukemia.
Use of any other experimental drug or therapy within 14 days or 5 half-lives (whichever is shorter) of first dose of study drug treatment.
Subjects who have had anti-cancer therapies within 14 days or 5 half-lives (whichever is shorter) prior to first dose of study drug.
Subject with chronic medical conditions requiring prohibited medications described below and listed in the Concomitant Medications Section 7.
• Subjects receiving treatment with Strong CYP3A4 inhibitors in the form of antifungal therapy will be enrolled into a separate treatment arm as described in the Study Design Section 3.1.
Subjects with any GI surgery or GI medical condition that could impact upon the absorption of the study drug.
Subjects with clinically significant cardiac disease (NY Heart Association Class III or IV, Appendix 4).
Subjects with a known allergy to SGR-2921 or its components.
Subjects with QT interval corrected for heart rate per Fridericia’s formula (QTcF) ≥470 msec during screening electrocardiogram (ECG). Two additional ECGs may be obtained when a single screening ECG demonstrates a QTcF ≥ 470 msec. In this case, the QTcF can be determined based on the mean of the triplicate recordings. Alternatively, the patient may repeat the ECG on a subsequent date for eligibility. Subjects with an underlying bundle branch block may be eligible upon discussion with the Medical Monitor.
Females of child-bearing potential who are pregnant, breast-feeding or intending to become pregnant during study treatment or up to 90 days after the last dose of study treatment.
Subject has any other medical condition (metabolic dysfunction, physical examination finding, or clinical laboratory finding), significant infection (acute bacterial, viral, or fungal) or any other condition which would interfere with full participation in the study (including administration of study treatment, attending required study visits, or allowing procedures), that in the Investigator’s opinion, places the subject at unacceptable risk of participation in the study.
Subjects who have received strong non-azole CYP3A4 inhibitors within 14 days or 5 half-lives (whichever is shorter) prior to the first dose of study drug.
