IRB Study Number 23-1226
Status Recruiting
Institute Taussig Cancer Institute
Description
Primary Objective
• To characterize the safety and tolerability of AB521 monotherapy in participants with advanced solid tumor malignancies and clear cell renal cell carcinoma (ccRCC)
Secondary Objectives
• To assess the clinical activity of AB521 monotherapy
• To characterize the pharmacokinetics (PK) of AB521
Inclusion Criteria
Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
Male or female participants ≥ 18 years of age (or at least the age that is regionally approved age of consent for participation in investigational clinical studies) at the time of signing the ICF.
Disease-specific criteria for dose escalation:
a. Participants may have any pathologically confirmed solid tumor type where no other treatment options are available, and
b. Creatinine clearance ≥ 40 mL/min as determined by Cockcroft-Gault equation (Cockcroft and Gault 1976) or other acceptable method.
- Disease-specific criteria for dose-expansion:
a. Histologically confirmed ccRCC and,
a. Must have received prior treatment in the metastatic setting (either individually or in combination) with an anti-PD-1/PD-L1 therapy and a TKI, and
b. No prior treatment with an HIF-2α-targeting therapy;
c. Creatinine clearance ≥ 40 mL/min as determined by Cockcroft-Gault equation (Cockcroft and Gault 1976) or other acceptable method.
Must have at least 1 measurable lesion per RECIST guidance (Version 1.1; see Appendix 5 in Section 10.5).
Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 1 (see Appendix 4 in Section 10.4).
Negative tests for hepatitis B surface antigen and hepatitis C virus antibody (or hepatitis C qualitative RNA [qualitative]) at screening. COVID-19 negative test as required by regional policy or site standard operating procedures (SOPs). Note: Participants with treated hepatitis B and/or C with no evidence of active infection may be enrolled.
Adequate organ and marrow function including:
a. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
b. Platelet count ≥ 100 × 109/L
c. Hemoglobin ≥ 10.0 g/dL (or 6.2 mmol/L)
d. Aspartate transaminase (AST) ≤ 2.5 × ULN without hepatic metastasis and ≤ 5 × ULN with hepatic metastasis
e. Alanine aminotransferase (ALT) ≤ 2.5 × ULN without hepatic metastasis and ≤ 5 × ULN with hepatic metastasis
f. Bilirubin ≤ 1.5 × ULN (except participants with Gilbert syndrome who must have total bilirubin < 3.0 mg/dL).
Screening ambulatory oxygen saturation (SpO2) ≥ 92%.
No radiological evidence of pneumonitis at screening.
No medical history of severe chronic obstructive pulmonary disease (COPD).
No evidence of clinically significant pericardial effusion in screening echocardiogram or multigated acquisition scan (MUGA).
Sex and Contraceptive/Barrier Requirements
- Contraceptive use by males and females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
a. Male participants must use effective contraceptive methods during treatment and for 90 days post last dose and refrain from donating sperm during treatment and for 90 days post last dose (see Section 10.2 for additional information).
b. Given the potential effect on some hormonal contraceptives, females of childbearing potential who are using hormonal contraceptives must be willing to use a second effective non-hormonal method of contraception (eg, male condom, diaphragm with spermicide).
- A female participant is eligible to participate if she is not pregnant (Section 10.2), not breastfeeding, not planning to become pregnant, and at least one of the following conditions applies:
a. Not a woman of childbearing potential (WOCBP) as defined in Appendix 2 (Section 10.2) OR
b. A WOCBP who agrees to follow the contraceptive guidance in Appendix 2 (Section 10.2) during the treatment period and for 90 days post last dose and agrees to not donate ova during the treatment period and for 90 days post last dose.
Other Inclusions
- Willing and able to comply with the requirements and restrictions in this protocol.
Exclusion Criteria
Use of any live vaccines against infectious diseases (eg, influenza, varicella) within 4 weeks (28 days) of initiation of investigational product.
Underlying medical conditions that, in the investigator’s judgment, will make the administration of investigational product hazardous (eg, interstitial lung disease, active infections requiring antibiotics, recent hospitalizations with unresolved symptoms) or obscure the interpretation of toxicity determination or AEs.
History of trauma or major surgery within 28 days prior to the first dose of investigational product. (Note that placement of central venous access catheter [eg, port or similar] is not considered a major surgical procedure).
For monotherapy dose expansion: prior treatment with an HIF-2α inhibitor.
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
Positive serum pregnancy test at screening and prior to dosing on Cycle 1 Day 1 (WOCBP only).
Is pregnant or breastfeeding or trying to conceive or father children within the projected duration of the study, starting with the pre-screening or screening visit through 90 days after the last dose of study treatment.
Other prior malignancy active within the previous year except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix, breast, or prostate cancer. Also, indolent malignancies, including but not limited to early-stage chronic lymphocytic leukemia and follicular lymphoma, that don’t require anti-cancer treatment, could be allowed after discussion with the medical monitor.
Prior chemotherapy targeted small-molecule therapy, immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer), or biologic agents, or use of other investigational drugs (drugs not marketed for any indication) within 28 days or 5 half-lives (whichever is shorter) before investigational product administration.
QTc ≥480 msec using Fredericia’s correction (QTcF) (based on an average of triplicate recordings).
Known hypersensitivity to any excipient contained in the IP formulations.
Inability to swallow study treatment.
Malabsorption condition that would alter the absorption of orally administered medications.
