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jialin Qian
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JCSE01 - Joint IASLC-CSCO-CAALC Session (ID 63)
- Event: WCLC 2019
- Type: Joint IASLC-CSCO-CAALC Session
- Track:
- Presentations: 1
- Now Available
- Moderators:Chunxue Bai, Tony Mok, Yi-Long Wu, Qing Zhou, Nan Wu
- Coordinates: 9/07/2019, 07:00 - 11:15, Toronto (1985)
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JCSE01.11 - Efficacy and Safety of Sintilimab with Anlotinib as First-Line Therapy for Advanced Non-Small Cell Lung Cancer (NSCLC) (Now Available) (ID 3425)
07:00 - 11:15 | Author(s): jialin Qian
- Abstract
- Presentation
Abstract
Background
Given the synergy effect of immunotherapy and anti-angiogenic therapy in advanced NSCLC, FDA approved atezolizumab plus bevacizumab and chemotherapy as first-line treatment. However, chemo-free first-line strategy of PD-1/PD-L1 inhibitor combining angiogenesis modulator remains to be explored. This is the first trial evaluating sintilimab (anti-PD-1) plus anlotinib (multi-target TKI against tumor angiogenesis and proliferation) in treatment-naive advanced NSCLC patients and is one arm of Phase I anlotinib-based trial (NCT03628521).
Methods
Treatment-naive, stage IIIB/IV NSCLC patients aged 18-75 with ECOG PS 0-1 were eligible. Patients with EGFR, ALK or ROS1 mutations were excluded. Participants were given intravenous sintilimab (200mg q3w) and oral anlotinib (12mg/d 2 weeks on/1 week off) until progression or unacceptable toxicity. The primary endpoints were ORR and safety. The secondary endpoints included DCR, PFS and OS. AEs were graded according to CTCAE v4.0.
Results
From September-2018 to February-2019, 22 patients were enrolled. Most were male (95.5%), former/current smokers (63.6%) and squamous cell histology (54.5%). 4 had baseline brain metastases. All patients have received at least once tumor assessment as of Jul-3th-2019. Among all, 16 achieved confirmed PR, 6 achieved SD, ORR was 72.7% (49.8%, 89.3%) and DCR was 100% (84.6%, 100%). 6 month PFS rate is 93.8% (95%CI: 63.23%, 99.10%). Overall, sintilimab and anlotinib was well tolerated. 6 (27.3%) had grade 3 and above treatment related adverse event (TRAE). The most common TRAE included fecal occult blood, hyperuricemia, hyponatremia, foot-hand syndrome, etc. 21 patients had baseline PD-L1-evaluated and 18 patients got TMB status (details in table). Notably, 5 of 6 SD patients developed cavities inside, suggesting a synergetic anti-tumor effect from combination regimen.Conclusion
In this interim analysis, sintilimab plus anlotinib showed high ORR (72.7%) and DCR (100%) with tolerable safety profile, supporting worthy of further development from this convenient chemo-free regimen in first line setting.
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P1.04 - Immuno-oncology (ID 164)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.04-02 - Efficacy and Safety of Sintilimab with Anlotinib as First-Line Therapy for Advanced Non-Small Cell Lung Cancer (NSCLC) (ID 939)
09:45 - 18:00 | Author(s): jialin Qian
- Abstract
Background
Given the synergy effect of immunotherapy and anti-angiogenic therapy in advanced NSCLC, FDA approved atezolizumab plus bevacizumab and chemotherapy as first-line treatment. However, chemo-free first-line strategy of PD-1/PD-L1 inhibitor combining angiogenesis modulator remains to be explored. This is the first trial evaluating sintilimab (anti-PD-1) plus anlotinib (multi-target TKI against tumor angiogenesis and proliferation) in treatment-naive advanced NSCLC patients and is one arm of Phase I anlotinib-based trial (NCT03628521).
Method
Treatment-naive, stage IIIB/IV NSCLC patients aged 18-75 with ECOG PS 0-1 were eligible. Patients with EGFR, ALK or ROS1 mutations were excluded. Participants were given intravenous sintilimab (200mg q3w) and oral anlotinib (12mg/d 2 weeks on/1 week off) until progression or unacceptable toxicity. The primary endpoints were ORR and safety. The secondary endpoints included DCR, PFS and OS. AEs were graded according to CTCAE v4.0.
Result
From September-2018 to February-2019, 22 patients were enrolled. Most were male (95.5%), former/current smokers (63.6%) and squamous cell histology (54.5%). 4 had baseline brain metastases. All patients have received at least once tumor assessment as of Jul-3th-2019. Among all, 16 achieved confirmed PR, 6 achieved SD, ORR was 72.7% (49.8%, 89.3%) and DCR was 100% (84.6%, 100%). 6 month PFS rate is 93.8% (95%CI: 63.23%, 99.10%). Overall, sintilimab and anlotinib was well tolerated. 6 (27.3%) had grade 3 and above treatment related adverse event (TRAE). The most common TRAE included fecal occult blood, hyperuricemia, hyponatremia, foot-hand syndrome, etc. 21 patients had baseline PD-L1-evaluated and 18 patients got TMB status (details in table). Notably, 5 of 6 SD patients developed cavities inside, suggesting a synergetic anti-tumor effect from combination regimen.
Conclusion
In this interim analysis, sintilimab plus anlotinib showed high ORR (72.7%) and DCR (100%) with tolerable safety profile, supporting worthy of further development from this convenient chemo-free regimen in first line setting.
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P2.01 - Advanced NSCLC (ID 159)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.01-31 - Preliminary Results of Second Generation ALK Inhibitor PLB1003: A Phase La Study (Now Available) (ID 1741)
10:15 - 18:15 | Author(s): jialin Qian
- Abstract
Background
ALK rearrangements have been described in approximately 4-5% of patients with non-squamous non-small cell lung cancer (NSCLC). Crizotinib is initially effective in the treatment of ALK-rearranged NSCLC, but the disease eventually progresses. PLB1003, a high-efficiency second generation ALK inhibitor, was developed due to the increased resistance of EML4-ALK fusion genes. Preclinical data show that PLB1003 is safe and effective in cell-based assays and Crizotinib-resistant animal models. This is the ongoing phase Ia study of PLB1003.
Method
An open-label, multicenter phase I clinical trial was conducted in patients with locally advanced or metastatic NSCLC who had previously failed or were intolerable to Crizotinib or chemotherapy. It consisted of dose-escalation cohorts and dose-expansion cohorts. In the dose-escalation cohorts, patients were orally given 50-500mg/d of PLB1003 at 6 dose levels . In each cohort, patients' plasma were collected for pharmacokinetic evaluation. The safety, tolerability, pharmacokinetics, maximum tolerated dose (MTD), dose limiting toxicities (DLT) and recommended phase 2 dose (RP2D) of PLB1003 were determined.
Result
A total of 21 patients were enrolled in dose-escalation cohorts as of 31 August 2018. The dose-escalation cohort is ongoing at the dose of 200 and 250 mg BID. A lipase elevation of DLT event was observed at 250 mg BID. MTD has not been reached in this study. Additionally, the most common treatment-emergent adverse events (TEAEs) (>10%) were grade1/2, including: (1) gastrointestinal toxicities: diarrhea (24%), vomiting (14%); (2) hepatotoxicity: increased GGT (g-glutamyltransferase) (48%), increased ALP (33%), elevated ALT (43%) and AST (33%); (3) others: increased blood glucose level (43%), hyperuricemia (24%), increased creatinine (19%), anemia (19%), hypercholesterolemia (14%). All the treatment-related adverse events (TRAEs) were reversible. TRAEs of grade 3, increasing of GGT (-glutamyl transferase) (33%), alkaline phosphatase (10%) and lipase (10%) , mostly appeared during 7-13 weeks of initial study. Patients all recovered from TRAEs of grade 3 with symptomatic treatments. Among the 14 evaluable patients in ≥200mg/d cohorts, 10 patients had PR (71%), 2 patients had SD (14%), and the disease control rate (DCR) was 86%. Among the 7 patients who progressed with previous treatment of Crizotinib, 5 patients had PR (71%), 1 patient had SD (14%), and the DCR was 86%.
Conclusion
PLB1003 is safe, tolerable and has potential clinical benefit to locally advanced or metastatic NSCLC patients with ALK rearrangement mutation and had disease progression or were intolerable to previously treatment of Crizotinib or chemtherapy. (ClinicalTrials.gov number, NCT03130881)
