T-regulatory Cell Depletion with E7777 Combined with Pembrolizumab in Recurrent or Metastatic Solid Tumors
Trial Parameters
Brief Summary
Epithelial ovarian cancer (OC) is the most lethal gynecologic cancer: nearly 22,000 women are diagnosed with OC in the US annually and 63% are expected to die from their disease. The 5-year overall survival rate is unacceptably low at 20-30%, with \> 50% of patients experiencing recurrence of their disease. Recurrent, platinum-resistant OC is characterized by a low response to chemotherapy (\<10-15%) and poor prognosis, with overall survival estimated to be \<12 months. Thus, there is an urgent need to identify novel therapies to improve outcomes for patients with recurrent, platinum resistant OC. The primary focus in this trial is targeting tumor associated immunosuppressive T-regs with E7777 combined with PD-1 inhibitor, pembrolizumab. This trial will enroll patients with solid tumors in the dose escalation portion and specified cohorts in the dose expansion portion. In the Phase I portion, 18-30 patients will be enrolled. In the dose expansion portion, approximately 40 patients (20 in each cohort) will be enrolled. Given the relatively poor prognosis and limited treatment options for these patients, this population is considered appropriate for trials of novel therapeutic candidates.
Eligibility Criteria
Inclusion Criteria: * Ability to comply with the study protocol, in the investigator's judgment * Histologically or cytologically confirmed solid tumors (cutaneous melanoma, non-small cell lung cancer, renal cell carcinoma, endometrial cancer, ovarian cancer, MSI-H solid tumors (deficient mismatch repair system or other solid tumors) that have progressed on or refractory to standard of care therapies for their disease * Phase I dose escalation phase * Advanced metastatic or recurrent solid tumors (where pembrolizumab is approved and/or have shown efficacy) that have progressed on or refractory to standard of care therapies for their disease * Prior anti-PD1 or PDL1 therapy is allowed * Prior anti-CTLA4 therapy is allowed if had anti-CTLA4 free interval of 6 months or more * At least one prior line of therapy in the dose escalation phase * Phase Ib dose expansion cohorts * Platinum-resistant recurrent ovarian cancer (recurred within 6 months or less of prior platinum therapy) or post-PD