Abstract 1803P
Background
Some studies have demonstrated a synergistic antitumor effect with chemotherapy, PARP inhibitors and immune checkpoint inhibitors (ICIs). Novel combinations may overcome resistance in patients (pts) with solid tumors after failure on standard therapy.
Methods
A phase Ib study was designed to evaluate safety and efficacy of Cis combined with Sin and Nir in previously treated advanced solid tumors including lung squamous cell carcinoma (LUSC), esophageal squamous cell carcinoma (ESC), cervical squamous cell carcinoma (CSCC), small cell lung cancer (SCLC), ovarian cancer (OC). The study consisted of a dose escalation phase (part1) and a dose expansion phase (part 2). Dose escalation followed a 3 + 3 design to determine dose-limiting toxicities (DLT), maximum tolerated dose (MTD) and the recommended part 2 dose. Eligible pts will receive Sin and Cis on day 1, plus Nir daily, of a 21-day cycle for up to 4 cycles, following Sin and Nir until disease progression or intolerable toxicity (Table). DDR mutations were tested by NGS with a 733-gene panel. Primary endpoints are DLT and MTD. Secondary endpoints are ORR and safety Table: 1803P
Dose escalation
| Dose level | Dose regimen | N |
| Level 1 | Cis 40mg/m2 + Sin 200mg + Nir 100mg | 3 |
| Level 2 | Cis 60mg/m2+ Sin 200mg + Nir 100mg | 3 |
| Level 3 | Cis 60mg/m2+ Sin 200mg + Nir 200mg | 3 |
Dosing: Sin: 200 mg IV Q3W; Cis: 40 or 60 mg/m2 IV Q3W; Nir: 100 or 200 mg PO QD
.Results
From Jul to Dec 2019, 9 pts were enrolled in part 1, including 6 SCLC, 2 LUSC and 1 OC after 1 or 2L treatment failure. During the first cycle, no grade ≥3 hematological toxicities were reported except for a grade 3 leukopenia of the third pt in level 3. No grade ≥3 non-hematological toxicities occurred. 2 partial responses (PR) (2 SCLC, including 1 pt who had received nivolumab combined with ipilimumab as 2L treatment) and 3 stable disease (2 LUSC, 1 OC) were reported.
Conclusions
No DLTs observed in part one. The recommend expansion phase dose of Cis and Nir were 60 mg/m2 and 200 mg, respectively when combined with Sin 200 mg. Preliminary efficacy data show responses in SCLC pts. Part 2 of the study is ongoing.
Clinical trial identification
ChiCTR1900024488.
Editorial acknowledgement
Legal entity responsible for the study
Chinese PLA Genernal Hosiptal.
Funding
Zai Lab limited (Shanghai) co., LTD; Innovent Biologics (Suzhou) Co., Ltd.
Disclosure
All authors have declared no conflicts of interest.