1640TiP PECATI: A phase II trial to evaluate the efficacy and safety of lenvatinib in combination with pembrolizumab in pretreated advanced b3-thymoma (B3-T) and thymic carcinoma (TC)

The optimal treatment in patients (pts) with platinum refractory advanced B3-T and TC is not yet stablished. Both, sunitinib and lenvatinib (multi-tyrosine kinase inhibitors with antiangiogenic properties) have reported clinically meaningful results in this setting. Similarly, the immune checkpoint inhibitors have also demonstrated encouraging antitumor activity with durable response for pts with B3-T and TC. Lenvatinib (L) plus pembrolizumab (P) have reported synergistic activity in solid tumors such as renal cell carcinoma and endometrial cancer. We aim to assess the safety and efficacy of this combination in pts with advanced B3-T or TC who progressed on or after at least one previous line of platinum-based chemotherapy. PECATI (NCT04710628) is a multicentric, open-label, single-arm, phase 2 trial at 6 sites across Spain, France, and Italy. The study enrolls pts aged ≥ 18 years, ECOG performance status of 0–1, with advanced B3-T and TC and measurable lesions by RECIST v.1.1 criteria that progressed following at least one platinum-based chemotherapy, regardless of PD-L1 status. Previous treatment with immunotherapy or sunitinib is not allowed (previous bevacizumab is allowed). Pts receive L (20 mg orally daily) plus P (200 mg iv infusion once every 3 weeks) in 3-week cycles until disease progression, unacceptable toxicity, or patient refusal. Maximum duration of treatment is 35 cycles. In case of withdrawal of any of the agents due to toxicity, monotherapy is allowed as per investigator’s criteria. The primary endpoint is 5-month progression-free survival (PFS) rate. Secondary endpoints include PFS, objective response rate, disease control rate, duration of response, overall survival; and safety and toxicity profile as per NCI-CTCAE v.5.0. Exploratory endpoints include PD-L1 expression, blood tumor mutational burden, immune-related gene signatures, and genomic profiles at baseline and at the time of disease progression. The primary analysis estimates the 5-month PFS rate (H0 ≤ 50%; H1 ≥ 68.6%) based on the exponential maximum likelihood method. A sample size of 43 pts is needed to attain 80% power at a nominal one-sided α level of 5%. EudraCT 2020-00397-18. Medica Scientia Innovation Research (MedSIR). MSD Merck USA.