Pamiparib in combination with tislelizumab in patients with advanced solid tumours: results from the dose-expansion stage of a multicentre, open-label, phase I trial

Abstract

Background: The aim of this study was to investigate the antitumour activity, safety, and tolerability of pamiparib plus tislelizumab in patients with previously treated advanced solid tumours.

Methods: In this study, patients were enrolled into eight arms by tumour type. All received pamiparib 40 mg orally twice daily plus tislelizumab 200 mg intravenously every 3 weeks. The primary endpoint was objective response rate (ORR), assessed by the investigator per Response Evaluation Criteria in Solid Tumours v1.1. Secondary endpoints included duration of response (DoR), safety, and tolerability.

Results: Overall, 180 patients were enrolled. In the overall population, the ORR was 20.0% (range: 0-47.4 across study arms), with median DoR of 17.1 months (95% confidence interval [CI]: 6.2, not estimable [NE]). The highest ORR was observed in the triple-negative breast cancer (TNBC) arm (patients with BRCA1/2 mutations and/or homologous recombination deficiency) (ORR: 47.4%; median DoR: 17.1 months [95% CI: 3.0, NE]). Treatment-emergent adverse events (TEAEs) of ≥Grade 3 occurred in 61.7% of patients. Serious TEAEs occurred in 50.0% of patients.

Conclusions: Pamiparib plus tislelizumab showed a variable level of antitumour activity in patients with advanced solid tumours, with the highest ORR in TNBC and was associated with a manageable safety profile.

Clinical trial registration: ClinicalTrial.gov: NCT02660034.

Fig. 1. Maximum reduction from baseline in target lesion diameter per study arm.

*BRCAmut by central testing; ^†BRCAwt by central testing; ^‡BRCA unknown by central testing; ^§HRD by central testing; ^|HRP by central testing; ^¶HRD unknown by central testing. ^#Patients with non-ovarian gynaecological cancers (endometrial cancer or cancer of the cervix) and patients with tumours known to be mismatch repair deficient or HRD that are not eligible for inclusion in any other arms of the trial but that may be expected to benefit from the PARP/PD-1 inhibitor combination (see Supplementary Table S1 for the full list of cancer types enrolled in this arm). Dotted lines at −30% and 20% indicate the boundaries for disease response and progression, respectively. Data are presented only for patients with an evaluable post-baseline assessment of target lesions. Data cutoff: 25 September 2020. BRCAmut breast cancer type 1/2 susceptibility gene mutation, BRCAwt breast cancer type 1/2 susceptibility gene wildtype, CR complete response, EOC epithelial ovarian cancer, G/GEJ gastric or gastroesophageal junction, HER2− HER2 negative, HRD homologous recombination deficiency, HRP homologous recombination proficiency, mCRPC metastatic castration-resistant prostate cancer, PD-1 programmed cell death protein 1, PD progressive disease, PR partial response, SCLC small cell lung cancer, SD stable disease, TNBC triple-negative breast cancer.

Fig. 2. Progression-free survival and overall survival.

a Progression-free survival. b Overall survival. *Patients with non-ovarian gynaecological cancers (endometrial cancer or cancer of the cervix) and patients with tumours known to be mismatch repair deficient or HRD that are not eligible for inclusion in any other arms of the trial but that may be expected to benefit from the PARP/PD-1 inhibitor combination (see Supplementary Table S1 for the full list of cancer types enrolled in this arm). Data cutoff: 25 September 2020. BRCAmut breast cancer type 1/2 susceptibility gene mutation, BRCAwt breast cancer type 1/2 susceptibility gene wildtype, EOC epithelial ovarian cancer, G/GEJ gastric or gastroesophageal junction, HER2− HER2 negative, HRD homologous recombination deficiency, HRP homologous recombination proficiency, mCRPC metastatic castration-resistant prostate cancer, OS overall survival, PD-1 programmed cell death protein 1, PFS progression-free survival, SCLC small cell lung cancer, TNBC triple-negative breast cancer.