ICRA Trial Finds Synergy Between Paclitaxel, Tremelimumab for mUC

At the European Society for Medical Oncology Congress 2023, Dr. Sarah Einerhand presented new data on the ICRA trial to determine the efficacy of a paclitaxel combination treatment for metastatic urothelial carcinoma (mUC).

As the prognosis for patients with mUC after treatment with platinum-based chemotherapy and anti-PD-L1 regimens is poor, taxane-based treatments have been investigated due to their ability to inhibit the tumor microenvironment and provide disease control.

The clinical activity of anti-CTLA4 drugs such as tremelimumab has previously been reported, leading investigators to study the use of paclitaxel plus tremelimumab with or without durvalumab to determine if the combination could induce response in therapy-refractory patients with mUC.

Dr. Einerhand and fellow researchers from the Netherlands Cancer Institute utilized several phases during the ICRA trial, beginning with a safety run-in phase comprising 15 patients. Patients were given 1 of 2 treatments: weekly administrations of paclitaxel 70 mg/m² on days 1, 8, and 15 for 6 cycles plus tremelimumab 25 mg, 225 mg, or 750 mg administered for 2 to 8 cycles every 4 weeks, or paclitaxel plus durvalumab for 2 to 12 cycles every 4 weeks plus either tremelimumab 75 mg for 2 to 5 cycles every 4 weeks or a single 300-mg dose.

An expansion phase comprised 3 treatment arms, each with 12 patients. In arm A, patients received paclitaxel for 1 to 6 cycles plus tremelimumab 750 mg for 2 to 8 cycles. In arm B, patients were administered paclitaxel for 1 to 6 cycles plus tremelimumab in a single 300-mg dose on cycle 2, along with durvalumab 1500 mg on cycles 2 to 12. In arm C, patients were administered tremelimumab 750 mg on cycles 1 to 7.

Based on 2 responses, arm A was extended to 20 patients. The primary end point was objective response rate (ORR) with a target of 30% and an aim to exclude 10%. Safety was assessed using version 5 of the Common Terminology Criteria for Adverse Events.

The primary end point was met, with an ORR of 26% (88% CI, 14%-37%; 5/19 evaluable patients) in arm A. In arms B and C, the ORR was 8%. The median OS (95% CI) was 16 months (range, 4.4-27.5 months) in arm A, 13.9 months (range, 9.5-18.3 months) in arm B, and 6.6 months (range, 0.0-14.8 months) in arm C (P=0.68). The median progression-free survival was 5.7 months in arm A (range, 4.0-7.3 months), 6.5 months in arm B (range, 3.7-9.4 months), and 2.8 months in arm C (range, 0.0-5.7 months; P=.27).

The ICRA trial found that in heavily pretreated patients with mUC, paclitaxel administered with tremelimumab 750 mg provided encouraging antitumor activity with a manageable safety profile, suggesting synergy between taxanes and high-dose anti-CTLA4 drugs.