scholarly journals Efficacy and Safety of Sintilimab Plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC: a Randomized, Double-Blind, Phase 3 Study (Oncology pRogram by InnovENT anti-PD-1-11)

2020 ◽  
Vol 15 (10) ◽  
pp. 1636-1646 ◽  
Author(s):  
Yunpeng Yang ◽  
Zhehai Wang ◽  
Jian Fang ◽  
Qitao Yu ◽  
Baohui Han ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Line Treatment ◽  
Efficacy And Safety ◽  
First Line ◽  
Phase 3 ◽  
Double Blind ◽  
Nonsquamous Nsclc ◽  
First Line Treatment

Efficacy and safety of IBI305 compared with bevacizumab in advanced non-squamous NSCLC patients as first-line treatment in a randomized, double-blind, phase III study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9095-9095
Author(s):  
Li Zhang ◽  
Bin Wu ◽  
Linian Huang ◽  
Meiqi Shi ◽  
Yunpeng Liu ◽  
...  
Keyword(s):  
Comparative Study ◽  
Maintenance Treatment ◽  
Line Treatment ◽  
Efficacy And Safety ◽  
First Line ◽  
Phase 3 ◽  
Double Blind ◽  
Nsclc Patients ◽  
Equivalence Margin ◽  
First Line Treatment

9095 Background: IBI305 is a recombinant humanized anti-VEGF monoclonal antibody, a biosimilar candidate to bevacizumab in analytical and functional comparisons. Pharmacokinetic similarity has been demonstrated in healthy males. Here we present primary efficacy and safety results from a phase 3 comparative study in non-small cell lung cancer (NSCLC). Methods: In this double-blind, active-controlled study, subjects with advanced non-squamous NSCLC on first-line treatment with carboplatin and paclitaxel were randomized (1:1) to IBI305 or bevacizumab (15 mg/kg IV Q3W). After six cycles, patients were on maintenance treatment with IBI305 or bevacizumab (7.5 mg/kg IV Q3W) till progression. Clinical equivalence of the primary endpoint, confirmed objective response rate (ORR) was evaluated by comparing the 2-sided 90% confidence interval (CI) of the risk ratio (RR) between study arms with the prespecified margin (0.75, 1.33). Results: A total of 450 subjects were randomized (IBI305: n = 224; bevacizumab: n = 226). Baseline characteristics were well balanced between treatment arms. ORR evaluated by Independent Radiological Review Committee (IRRC) in full analysis set (FAS) was 44.3% (98/221) for IBI305 and 46.4% (102/220) for bevacizumab; the RR for ORR was 0.95 (90% CI: 0.803, 1.135). Sensitive analysis result on RRs of ORR in Intention to Treat (ITT) population (IBI305: n = 224; bevacizumab: n = 226) and other analysis set were consistent and all within the prespecified equivalence margin. The medium PFS were 8.4 months for IBI305 and 8.3 months for bevacizumab and duration of response (DOR) was also similar in both arms. Treatment-emergent adverse events (TEAEs) were well balanced between treatment arms and consistent with the known adverse event profile of bevacizumab. Patients developing binding antibodies were 0.5% in the IBI305 arm vs 0% in the bevacizumab arm; no subject tested positive for neutralizing antibodies. Conclusions: This is the first released phase 3 clinical study with maintenance treatment for bevacizumab biosimilar in NSCLC patients till now. The comparative study met its predefined primary endpoint that the RR for confirmed ORR was within the prespecified equivalence margin. There was no significant difference between the two arms in safety profile and immunogenicity. Clinical trial information: NCT02954172.

Masitinib plus gemcitabine as first-line treatment of pancreatic cancer with pain: Results from phase 3 study AB12005.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4018-4018
Author(s):  
Joel Ezenfis ◽  
Olivier Hermine ◽  
Keyword(s):  
Pancreatic Cancer ◽  
Statistical Significance ◽  
Locally Advanced ◽  
Disease Stage ◽  
Study Cohort ◽  
Line Treatment ◽  
First Line ◽  
Phase 3 ◽  
Risk Of Death ◽  
First Line Treatment

4018 Background: Masitinib (MAS) is a small molecule drug targeting mast cell and macrophage activity, innate immune cells that are critical components of the tumor microenvironment. Proof of concept that MAS in combination with gemcitabine (GEM) improved overall survival (OS) in pancreatic cancer (PC) patients (pts) with pain, was previously shown [doi 10.1093/annonc/mdv133]. The presence of pain in PC is thought to identify pts whose disease is driven in part by a pro-tumoral immune response. Methods: AB12005 was a prospective, placebo (PBO) controlled, double blind, randomized (2:1 MAS:PBO, stratified by disease stage, ECOG and geographic region) phase 3 trial, evaluating oral MAS (6.0 mg/kg/d) in combination with GEM (1000 mg/m²) against PBO plus GEM for the treatment of unresectable locally advanced PC (LAPC) and/or metastatic PC (mPC) pts with pain criteria; i.e. baseline visual analog scale of pain intensity (VAS) > 20 and/or pt treated with an opioid analgesics dose ≥1 mg/kg/d at baseline. Eligible pts were chemo-naïve with histologically or cytologically confirmed inoperable LAPC or mPC and an ECOG status ≤2. The estimated sample size was ̃330 pts to detect an OS hazard ratio (HR) of 0.68 (80% power, 2-sided α = 0.025) after 310 deaths. The study was successful if improvement in median OS (primary endpoint) relative to control reached a 2.5% level of statistical significance for either a targeted subgroup of LAPC with pain criteria, or the overall study cohort. Results: A total of 384 pts were enrolled (safety population n = 383; mITT n = 379; target subgroup n = 92). In the predefined subgroup of unresectable LAPC with pain, MAS-GEM (n = 62) showed significant benefit over PBO-GEM (n = 30) with median OS of 13.0 months (97.5% CI [11.0;18.0]) vs 11.2 months (97.5% CI [7.4;13.0]); p = 0.007. The HR was 0.46 (97.5% CI [0.2;0.9], p = 0.0047), corresponding to a significant 54% reduction in risk of death for MAS-GEM pts relative to control. Secondary analyses in the same subgroup were convergent with this primary outcome. Median PFS showed a 1.8 month between group difference in favor of MAS-GEM (p = 0.039), with a HR of 0.47 (97.5% CI [0.3;0.9], p = 0.014). The 12-month and 18-month OS rates showed a 1.3 fold and 3.4 fold improvement, respectively, in favor of MAS-GEM (53.2% and 33.9% for MAS-GEM vs 40.0% and 10% for PBO-GEM, respectively). In the overall population, comprising LAPC and mPC pts with pain, no survival benefit was observed; median OS for MAS-GEM (n = 244) was 6.9 months vs 8.0 months for PBO-GEM (n = 135); p = 0.461. The MAS-GEM combination was well tolerated with no sign of add-on toxicity. The proportion of patients presenting at least one adverse event (AE) or serious AE was respectively, 96.3% and 19.1% for MAS-GEM (n = 246) vs 99.3% and 21.3% for PBO-GEM (n = 136). Conclusions: The combination MAS (6.0 mg/kg/d) plus GEM may provide a new first line treatment option for unresectable LAPC pts with associated pain. Clinical trial information: NCT03766295.

JUPITER-02: Randomized, double-blind, phase III study of toripalimab or placebo plus gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (NPC).

2021 ◽  
Vol 39 (18_suppl) ◽  
pp. LBA2-LBA2
Author(s):  
Rui-hua Xu ◽  
Hai-Qiang Mai ◽  
Qiu-Yan Chen ◽  
Dongping Chen ◽  
Chaosu Hu ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Double Blind ◽  
Grade 3 ◽  
First Line Treatment

LBA2 Background: Gemcitabine-cisplatin (GP) chemotherapy is the standard 1st line treatment for locally advanced, recurrent or metastatic (r/m) NPC. Toripalimab, a humanized IgG4K monoclonal antibody specific for PD-1, provided durable responses in patients (pts) with r/m NPC as monotherapy in the ≥2nd line setting (POLARIS-02 study). The results of JUPITER-02, a randomized, placebo-controlled, double-blinded Phase III trial of toripalimab in combination with GP chemotherapy as first-line treatment for r/m NPC are summarized. Methods: Pts with advanced NPC with no prior chemotherapy in the r/m setting were randomized (1:1) to receive toripalimab 240 mg or placebo d1 in combination with gemcitabine 1000 mg/m2 d1, d8 and cisplatin 80 mg/m2 d1 every 3 weeks (Q3W) for up to 6 cycles, followed by monotherapy with toripalimab or placebo Q3W until disease progression, intolerable toxicity, or completion of 2 years of treatment. Stratification factors were ECOG PS (0 vs. 1) and extent of disease (recurrent vs. primary metastatic) at enrollment. Progression-free survival (PFS) and response were assessed by independent review committee (IRC) per RECIST v1.1. The primary endpoint was PFS by IRC in the ITT population. Secondary end points included ORR, DOR and OS. There was one prespecified interim analysis of PFS at 130 PFS events with a planned final analysis at 200 PFS events. Results: 289 pts were randomized: 146 to the toripalimab arm and 143 to the placebo arm. By May 30, 2020 as the interim analysis cutoff date, the median treatment duration was 39 weeks in the toripalimab arm and 36 weeks in the placebo arm. A significant improvement in PFS was detected for the toripalimab arm compared to the placebo arm (HR = 0.52 [95% CI: 0.36-0.74] two-sided p = 0.0003), with median PFS of 11.7 vs. 8.0 months. The 1-year PFS rates were 49% and 28% respectively. An improvement in PFS was observed across relevant subgroups, including all PD-L1 subgroups. The ORR was 77.4% vs. 66.4% (P = 0.033) and the median DOR was 10.0 vs. 5.7 months (HR = 0.50 [95% CI: 0.33-0.78]). As of Jan 15, 2021, OS was not mature, with 25 deaths in the toripalimab arm and 35 in the placebo arm (HR = 0.68 [95% CI: 0.41-1.14], P = 0.14). The incidence of Grade ≥3 adverse events (AEs) (89.0% vs 89.5%); AEs leading to discontinuation of toripalimab/placebo (7.5% vs 4.9%); and fatal AEs (2.7% vs 2.8%) were similar between two arms; however, immune-related (irAEs) (39.7% vs. 18.9%) and Grade ≥3 irAEs (7.5% vs. 0.7%) were more frequent in the toripalimab arm. Conclusions: The addition of toripalimab to GP chemotherapy as 1st-line treatment for pts with advanced NPC provided superior PFS and ORR and longer DOR than GP alone with a manageable safety profile. These results support the use of toripalimab with GP chemotherapy as the new standard care for this population. Clinical trial information: NCT03581786.

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