Abstract 85P
Background
First-line chemo-immunotherapy has shown significant survival improvement in ES-SCLC, however, rapid drug resistance frequently occurs. Sitravatinib (Sitra), a selective tyrosine kinase inhibitor targeting TAM, VEGFR2 and KIT, can alter immune landscape to favor immunotherapy and overcome resistance. This single-arm, phase Ⅱ trial evaluated the efficacy and safety of tislelizumab (TIS, a PD-1 inhibitor) plus Sitra as maintenance therapy in ES-SCLC patients (pts) after induction therapy with TIS plus chemotherapy (chemo), aiming to postpones disease progression.
Methods
Eligible pts with untreated ES-SCLC received TIS (200 mg) plus platinum–based chemo Q3W for 4 cycles (induction), followed by maintenance TIS 200 mg Q3W and Sitra 70 mg daily. Maintenance analysis set (MAS) included pts who received ≥1 dose maintenance therapy. Efficacy outcomes in MAS were calculated from the start of maintenance TIS+Sitra. The primary endpoint was 1-year PFS rate per RECIST v1.1 in MAS.
Results
Between March 2022 and August 2022, 21 pts were enrolled and received induction therapy. Of these, 18 pts entered maintenance phase, with 27.8% having liver metastases, 27.8% bone metastases, 16.7% brain metastasis, and 94.4% ECOG PS 1. As of 21 Jul 2023, among the 18 pts in MAS, median PFS was 6.4 months and 1-year PFS rate was 27.8% from the start of maintenance therapy. Median OS was not reached. In MAS, 4 pts achieved further PR during maintenance therapy, yielding a confirmed ORR of 22.2%, and the DCR was 88.9%. In MAS, TRAEs and irAEs of grade 3-4 occurred in 10 (55.6%) and 2 (11.1%) pts, respectively. Serious TRAEs occurred in 4 (22.2%) pts. No TRAEs led to treatment discontinuation or death. Table: 85P
| Maintenance analysis set, N=18 | Induction analysis set∗, N=21 | |
| Efficacy | ||
| Confirmed ORR, % (95% CI) | 22.2 (6.4, 47.6) | 76.2 (52.8, 91.8) |
| DCR, % (95% CI) | 88.9 (65.3, 98.6) | 95.2 (76.2, 99.9) |
| Median DoR, months (95% CI) | 7.6 (5.3, NR) | 7.9 (6.0, 10.4) |
| Median PFS, months (95% CI) | 6.4 (4.5, 9.0) | 9.1 (7.3, 11.8) |
| 1-year PFS rate, % (95% CI) | 27.8 (10.1, 48.9) | 26.3 (9.6, 46.8) |
| 1-year OS rate, % (95% CI) | 59.4 (27.9, 80.9) | 65.3 (40.5, 81.8) |
| Safety | ||
| Grade 3-4 TRAEs, n (%) | 10 (55.6) | 18 (85.7) |
| Grade 3-4 irAEs, n (%) | 2 (11.1) | 2 (9.5) |
∗Defined as pts who received ≥1 dose of induction therapy; efficacy outcomes in induction analysis set were calculated from the start of induction therapy. NR=not reached
Conclusions
TIS plus Sitra showed promising efficacy with manageable toxicities as maintenance therapy in ES-SCLC pts after induction TIS+chemo. It provides a new treatment strategy to delay drug recurrence and prolong the survival for ES-SCLC pts.
Clinical trial identification
NCT05228496.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
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