A Phase 1, Open Label, Dose-Escalation and Expansion Study to Evaluate Safety, Pharmacokinetics and Initial Therapeutic Activity of AVA6103, a Novel FAP-activated Exatecan Administered Intravenously in Subjects With Locally Advanced or Metastatic Selected Solid Tumors
This is a first-in-human (FIH), Phase 1 open-label, multicenter dose escalation study investigating AVA6103 monotherapy administered intravenously in patients with locally advanced (unresectable) or metastatic solid tumors that are likely to be FAP positive. The study consists of an initial Phase 1a dose escalation portion and a subsequent Phase 1b dose expansion portion upon completion of the dose escalation portion.
• The subject is fully informed about the study and is willing and able to sign the informed consent form (ICF).
• Male or female subjects, ≥18 years of age.
• Subjects with the following tumors reported to be FAP positive, with histological or cytological confirmation of a locally advanced (unresectable) and/or metastatic progressing disease that have received all standard-of-care or Food and Drug Administration (FDA) approved treatments, or are ineligible for those treatments, or decline those treatments
∙ Cervical/vulvar cancer
‣ SCLC
‣ Gastric/GEJ cancer
‣ PDAC
‣ CRC
‣ HR+ breast cancer
• Has a life expectancy of ≥3 months, in the opinion of the investigator.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Has recovered from all acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedure (must have resolved to CTCAE Grade ≤1 or returned to baseline, whichever is greater. Exceptions include alopecia and peripheral neuropathy, which can be up to CTCAE Grade 2).
• Has adequate hematological function (applies only to subjects not receiving therapeutic anticoagulation; subjects receiving therapeutic anticoagulation should be on a stable dose):
∙ Absolute neutrophil count of ≥1.5 × 109 cells/L. Subjects with documented benign ethnic neutropenia may be enrolled with an absolute neutrophil count of ≥1.0 × 109 cells/L
‣ Hemoglobin ≥9.0 g/dL.
‣ Platelet count of ≥100,000/µL.
‣ International normalized ratio and activated partial thromboplastin time ≤1.5 times the ULN, except for subjects on direct acting anticoagulation.
• Has adequate liver function:
∙ Total bilirubin 1.5 × ULN (except for subjects with documented Gilbert's Syndrome or liver metastases who must have a total bilirubin \<3 × ULN).
‣ AST and ALT ≤2.5 × ULN (in subjects with liver metastases, \<5 × ULN is allowed).
• Has adequate renal function as defined by creatinine clearance ≥ 60 mL/min by the Cockcroft-Gault equation.
⁃ Women of childbearing potential and women who have ≤2 years amenorrhea after start of menopause, must have a negative serum or urine pregnancy test within 7 days prior to Cycle 1 Day 1.
⁃ Contraception requirements:
• Female subjects of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use a highly effective contraceptive method (Pearl Index failure rate \< 1% per year) during the treatment period and for at least 6 months after the last dose of study drug.
∙ Male subjects with female partners of childbearing potential must agree to using 2 acceptable methods of contraception (Pearl Index failure rate \<1% per year), including a barrier method (with or without spermicide) during the treatment period and for at least 6 months after the last dose of study drug.
∙ Male subjects must agree to refrain from sperm donation during the treatment period and for at least 6 months after the last dose of study drug.
⁃ The subject is willing and able to comply with the protocol, including any PK blood sampling and tumor biopsy requirements and agrees to return to clinic for follow-up visits and examinations.
• For subjects in Phase 1a or 1b, on treatment tumor biopsy is optional. -