A Phase Ib/II Single Arm Study of Cabozantinib Plus Dostarlimab in Women With Recurrent Gynecologic Carcinosarcoma
Immunotherapy has gained a significant amount of attention recently, but its efficacy as a single agent in gynecological cancers has been disappointing. Pre-clinical evidence supports the combination of using Vascular Endothelial Growth Factors (VEGF) inhibitors with immunotherapy. VEGF inhibitors suppress the activation of tumor-associated macrophages (TAMs) and VEGF has been shown to affect the functional maturation of dendritic cells; therefore, VEGF inhibitors could improve the function of antigen presentation. In this study, Cabozantinib (VEGF inhibitor) and Dostarlimab (immunotherapeutic drug) will be admnistered as a combination to patients with recurrent gynecologic carcinosarcoma.
• Histologically confirmed diagnosis of carcinosarcoma (independent of organ of gynecologic origin)
• Received at least one prior chemotherapy regimen for their cancer
• Must have measurable or evaluable lesion defined by iRECIST
• Recovery to baseline or ≤ Grade 1 CTCAE v5.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy
• ECOG Performance Status of 0-2
• Age ≥ 18 years
• Adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 14 days before first dose of study treatment:
∙ Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥ 1.5 GI/L) without granulocyte colony-stimulating factor support.
‣ White blood cell count ≥ 2500/mm3 (≥ 2.5 GI/L).
‣ Platelets ≥ 100,000/mm3 (≥ 100 GI/L) without transfusion.
‣ Hemoglobin ≥ 9 g/dL (≥ 90 g/L).
‣ Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 3 x upper limit of normal (ULN). ALP ≤ 5 x ULN with documented bone metastases.
‣ Total bilirubin ≤ 1.5 x ULN (for patients with Gilbert's disease ≤ 3 x ULN).
‣ Serum albumin ≥ 2.8 g/dl.
‣ Serum creatinine ≤ 2.0 x ULN or calculated creatinine clearance ≥ 30 mL/min (≥ 0.5 mL/sec) using the Cockcroft-Gault equation:
• \[(140 - age) x weight (kg)/(serum creatinine \[mg/dL\] × 72)\] × 0.85 i. Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol).
• Capable of understanding and complying with the protocol requirements and must have signed the informed consent document.
• Women of childbearing potential (WOCBP) ie. sexually active fertile patients and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 5 months after the last dose of study treatment.
⁃ Females should not breastfeed while receiving treatment on trial.
⁃ Female patients of childbearing potential must not be pregnant at screening. Females of childbearing potential are defined as premenopausal females capable of becoming pregnant (i.e., females who have had any evidence of menses in the past 12 months, with the exception of those who had a prior hysterectomy). However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, low body weight, ovarian suppression, or other reasons.