Spots Global Cancer Trial Database for Naptumomab Estafenatox in Combination With Pembrolizumab Preceded by Obinutuzumab in Patients With Urothelial Cancers

Study Description

Brief Summary: The main purpose of this study is to test the safety and tolerability of naptumomab estafenatox (NAP), the planned experimental (investigational) drug, in combination with pembrolizumab following a single pretreatment with Obinutuzumab (Obi), and determine its side effects and effects on urothelial cancer. It is hypothesized that adding NAP will make pembrolizumab more effective. Participants will receive 2 infusions of Obi prior to the treatment of NAP in combination with pembrolizumab. This treatment is given in 21-day cycles for 6 cycles with NAP administered daily for 4 consecutive days, Days 1-4, + pembrolizumab given on day 2 of each cycle. After these six cycles of therapy, participants will continue to receive pembrolizumab every 3 weeks, without NAP, for a total number of up to 34 pembrolizumab administrations since cycle 1. After the treatment of Obi is completed, participants will start NAP in combination with pembrolizumab and continue that treatment in a 28 day cycle period. NAP will be given for a total of 6 cycles and pembrolizumab will be given every 21 days for a total of up to 2 years. After stopping treatment, participants have follow-up visits or phone calls about every 12 weeks until the study is closed.

Detailed Description: This is a Phase 1, open-label, prospective, dose-finding and cohort expansion study to assess the safety, tolerability, pharmacodynamics and preliminary antitumor activity of the combination of NAP/pembrolizumab following pretreatment with Obi in patients with urothelial cancers who are candidates for pembrolizumab treatment. and will not be used to determine eligibility for enrollment. The study will test two doses of NAP 5 µg/kg/day (Dose Level 1) and 10 µg/kg/day (Dose Level 2), in combination with a fixed dose of pembrolizumab (200mg every 3 weeks). It is expected that full dose of both drugs can be safely combined. The purpose of this study is to define the recommended dose for phase 2 trials of the combination of NAP/pembrolizumab by employing a BOIN design for phase 1 trials. The BOIN design will find the highest dose for which the probability of a dose-limiting toxicity is less than 0.25. No dose level will have more than 12 patients. An initial cohort of 3 patients will be enrolled on Dose Level 1. After these patients have been observed for a DLT, the decision to escalate, de-escalate or remain at the current dose will be made according to the table in the statistical section of the protocol. The maximum tolerated dose (MTD) will be selected using isotonic regression that pools the information across doses. No intra-patient dose escalation is permitted. Patients who discontinue the study during the 21-day dose-limiting toxicity (DLT) observation period for reasons other than a DLT, or who do not receive a full cycle of NAP/pembrolizumab, will be replaced. Each patient will participate in 3 stages of the trial: a 21-day screening stage, followed by a treatment stage that may continue until evidence of progressive neoplastic disease, intolerance to treatment of fulfillment of any of the other criteria for treatment discontinuation as listed in Section 8.1 of the protocol, and a follow-up phase to determine the effect of protocol treatment on cancer progression. All patients will be seen at the end of treatment (EOT) visit 30 (+ 7) days after the last dose of protocol therapy.

Keywords

Eligibility

Minimum Age: 18 Years

Eligible Ages: ADULT, OLDER_ADULT

Sex: ALL

Healthy Volunteers: No

Locations

Contact Details

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