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Jian Fang
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OA04 - New Data from Rare EGFR Alterations (ID 223)
- Event: WCLC 2020
- Type: Oral
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/29/2021, 11:45 - 12:45, Scientific Program Auditorium
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OA04.03 - Mobocertinib in NSCLC With EGFR Exon 20 Insertions: Results From EXCLAIM and Pooled Platinum-Pretreated Patient Populations (ID 3186)
11:45 - 12:45 | Author(s): Jian Fang
- Abstract
- Presentation
Introduction
Mobocertinib is a potent first-in-class tyrosine kinase inhibitor (TKI) designed to target EGFR exon 20 insertion (EGFRex20ins) mutations. We report first results from the EXCLAIM extension cohort of a phase 1/2 study (NCT02716116) and results in patients with EGFRex20ins-mutant NSCLC who received prior platinum-based therapy from the dose-escalation/expansion parts of the study and the EXCLAIM extension cohort.
Methods
This 3-part, open-label, multicenter study included dose-escalation/expansion cohorts and the EXCLAIM extension cohort. Data are presented for all patients treated in EXCLAIM (N=96) and for platinum-pretreated patients from the dose-escalation/expansion cohorts (n=28) and from EXCLAIM (n=86); all received mobocertinib 160 mg orally QD. Enrolled patients had locally advanced/metastatic EGFRex20ins NSCLC, ECOG performance status 0–1, and ≥1 prior line of therapy for locally advanced/metastatic disease. The primary endpoint is confirmed ORR assessed by IRC per RECIST v1.1.
Results
In EXCLAIM, 96 patients were enrolled and treated; median age, 59 years [range: 27–80]; female, 65%; Asian, 69%; ≥2 prior systemic anticancer lines, 49% (range: 1–4). Median time on treatment was 6.5 months (range: 0–14). Confirmed ORR was 23% (22/96; 95% CI: 15%–33%) per IRC and 32% (95% CI: 23%–43%) per investigator; median DoR (Kaplan-Meier estimates) was not mature; median PFS was 7.3 months. See Table. In the analysis of platinum-pretreated patients (n=114), median age, 60 years [range: 27–84]; female, 66%; Asian, 60%; ≥2 prior systemic anticancer lines, 59% (range: 1–7). Median time on treatment was 7 months (range: 0–31); 38 patients (33%) remained on treatment as of 29-May-2020. Confirmed ORR was 26% (30/114; 95% CI: 19%–35%) per IRC and 35% (40/114; 26%–45%) per investigator. Median PFS was 7.3 months: 12-month PFS rate was 33% (95% CI: 21%–47%). Responses were observed among all prespecified subgroups, including Asian/non-Asian patients and those with/without baseline stable brain metastases. The most common treatment-related adverse events (TRAEs; ≥30%): diarrhea (90%), rash (45%), paronychia (34%), nausea (32%), decreased appetite (32%), dry skin (30%), and vomiting (30%); grade ≥3 TRAEs (≥5%): diarrhea (22%), anemia (5%), and dyspnea (5%). Nineteen patients (17%) discontinued due to AEs, most commonly diarrhea (4%) and nausea (4%). The safety profile observed in EXCLAIM was largely consistent with that observed in the platinum-pretreated population.
Conclusion
Mobocertinib demonstrated clinically meaningful benefit in previously treated patients with NSCLC and EGFRex20ins mutations, with a manageable safety profile.
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P09 - Health Services Research/Health Economics - Real World Outcomes (ID 121)
- Event: WCLC 2020
- Type: Posters
- Track: Health Services Research/Health Economics
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P09.29 - Immune-Related Adverse Events and their Association with Effectiveness of PD-1/PD-L1 Inhibitors in NSCLC: A Real-World Study from China (ID 2086)
00:00 - 00:00 | Author(s): Jian Fang
- Abstract
Introduction
Programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors are increasingly used in China, but no real-world data are available about the immune-related adverse events (irAEs). This real-world retrospective study aimed to assess the safety and effectiveness of PD-1/PD-L1 inhibitors in patients with non-small cell lung cancer (NSCLC) and to analyze the association between irAEs and effectiveness.
Methods
This was a retrospective study of the clinical information of patients with non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors from August 2016 to November 2019 at the Thoracic Medicine of Beijing Cancer Hospital.The patients were divided into irAE or non-irAE groups. Overall adverse events, impact of irAE on tumor response, and association of irAEs with effectiveness were evaluated.
Results
One hundred and ninety-one patients were included in this study, including 70 (36.6%) patients in IrAE Group and 121 (63.4%) patients in Non-irAE Group. AE, grade 3-5 AEs, and IrAE were occurred in 107 (56.0%), 24 (12.6%) and 70 (36.6%) of 191 patients respectively. The objective response rate (ORR) and disease control rate (DCR) were higher in irAE Group compared with Non-irAE Group (42.0% vs. 25.8%, P=0.038; 91.9% vs. 70.8%, P=0.002). Multivariable analyses identified irAE associated with progression-free survival (HR=0.62, 95%CI: 0.43-0.91; P=0.015), but not with overall survival (HR=0.76, 95%CI: 0.44-1.28; P=0.299).
Conclusion
In NSCLC treated with PD-1/PD-L1 inhibitors, patients with irAEs showed improved effectiveness over patients without irAEs. Future studies of anti-PD-1/PD-L1 immunotherapy should address this association to explore the underlying biological mechanisms of efficacy.
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P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P76.65 - CNS Efficacy of AST2818 in Patients with T790M-Positive Advanced NSCLC: Data from a Phase I-II Dose-Expansion Study (ID 3286)
00:00 - 00:00 | Author(s): Jian Fang
- Abstract
Introduction
Furmonertinib (AST2818, former name: alflutinib) is a new third-generation EGFR-tyrosine kinase inhibitor that selectively inhibits EGFR-sensitizing and EGFR T790M mutation. We have reported promising clinical activity and well-characterized tolerability of AST2818 in EGFR T790M-positive locally advanced or metastatic non-small-cell lung cancer (NSCLC) patients including its preliminary efficacy in patients with central nervous system (CNS) metastases (Shi Y et al JTO 2020;15(6):1015-1026). Herein, we report the result of recent subgroup analysis from phase I-II dose-expansion study (NCT03127449) where the CNS efficacy of different AST2818 doses was evaluated.
Methods
Patients aged ≥18 years with centrally confirmed EGFR T790M-positive locally advanced or metastatic NSCLC received AST2818 ranging from 40-240 mg doses once daily until disease progression. Patients with asymptomatic, stable CNS metastases not requiring steroids for at least 4 weeks before the first dose of AST2818 were enrolled. A subgroup analysis was conducted in patients with ≥1 measurable CNS lesion (per RECIST 1.1) at baseline brain imaging (CNS evaluable-for-response set, cEFR) and patients with ≥1 measurable and/or non-measurable CNS lesion at baseline brain imaging (CNS full analysis set, cFAS) by blinded independent central review (BICR). CNS efficacy was evaluated in terms of CNS objective response rate (ORR), CNS disease control rate (DCR), CNS progression-free survival (PFS), and CNS duration of response (DoR) (assessed by BICR).
Results
At data cutoff (29 January 2020), 116 patients were enrolled, of which 45 patients (38.8%) were included in cFAS and 23 patients (19.8%) were included in cEFR. Confirmed CNS ORR was 65.2% (15/23) while CNS DCR was 91.3% (21/23) in cEFR. The CNS ORR in the 40-, 80-, 160-, and 240-mg groups was 0 (no response of 1), 60% (3/5 partial response [PR]), 84.6% (1/13 complete response [CR] and 10/13 PR), and 25% (1/4 PR), respectively. In the cFAS, median CNS PFS was not reached (95% confidence interval [CI], 8.3 months to not reached), while median CNS PFS in 40-, 80-, 160-, and 240-mg groups were 2.8, 9.7, 19.3 months, and not reached, respectively. Median CNS DoR (19% maturity) in cFAS was not reached (range, 2.8 months to not reached). At 12 months, 50%, 81.8%, and 100% of patients were estimated to remain in response in 80-, 160-, and 240-mg groups, respectively.
Conclusion
AST2818 demonstrated clinically meaningful efficacy against CNS metastases. 160 mg provided relevant benefit with a high CNS ORR and PFS. Further studies are required to confirm these findings.
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P77 - Immunotherapy (Phase II/III Trials) - Combining Different Immunotherapeutic Approaches (ID 254)
- Event: WCLC 2020
- Type: Posters
- Track: Immunotherapy (Phase II/III Trials)
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P77.03 - A Phase II Study of KN046 (Bispecific Anti-PD-L1/CTLA-4) in Patients (pts) with Metastatic Non-Small Cell Lung Cancer (NSCLC) (ID 1665)
00:00 - 00:00 | Author(s): Jian Fang
- Abstract
Introduction
KN046 is a novel bispecific antibody that blocks PD-L1 interaction with PD1 and CTLA-4 interaction with CD80/CD86. This multiple-cohort, single-arm phase II study evaluates preliminary safety and efficacy of KN046 in subjects with metastatic non-small cell lung cancer (NSCLC).
Methods
Eligible patients (pts) were advanced NSCLC without EGFR mutation or ALK fusions, progressed on 1st line platinum-based chemotherapy but not treated with any PD-(L)1 immune checkpoint inhibitor. All pts were given KN046 3 mg/kg (Cohort A) or 5 mg/kg (Cohort B) Q2W IV up to disease progression, intolerable toxicity, etc. Efficacy evaluation was performed by investigators per RECIST 1.1 every 8 weeks and safety and tolerability assessed per NCI-CTCAE v5.0.
Results
As of the July 27, 2020, 30 pts enrolled in Cohort A and 33 in Cohort B. Median age 59 years, male/female 51/12, PS 0/1 9/54, squamous NSCLC/Non-squamous NSCLC 23/40. ≥ Grade 3 treatment related treatment emergent adverse events (TRAEs) were seen in 21 (33.3%) pts, treatment related severe adverse events (SAE) 16 (25.4%) pts, immune related adverse events (irAEs) 34 (54.0%) pts, ≥ Grade 3 irAEs 11 (17.5%) pts. Common (≥ 10%) TRAEs were infusion related reaction (16, 25.4%), anemia (14, 22.2%), rash (13, 20.6%), hyperglycemia (12, 19.0%), abnormal hepatic function (10, 15.9%), hypothyroidism (10, 15.9%), alanine aminotransferase increased (8, 12.7%), asthenia (8, 12.7%), aspartate aminotransferase increased (7, 11.1%) and pruritus (7, 11.1%). Safety profile was comparable between two cohorts.
As of cutoff date, 24 (37.5%) pts remained on the study treatment, and 39 (60.9%) pts discontinued treatment due to disease progression (n=27), AE (n=7), poor patient compliance (n=4) and one death. Median duration of drug exposure was 14 weeks (two to 56 weeks). ORR and DCR were 10.7% and 82.1%, 15.6% and 62.5% in cohort A and cohort B, respectively. Median PFS were 3.7 (2.9, 7.3), 3, 6 and 9-month PFS rate (95% CI) were 64.1% (49.4, 75.5), 36.6% (23.0, 50.4) and 34.2% (20.9, 47.9), 3, 6 and 9-month OS rate (95% CI) were 91.4% (80.5, 96.3), 86.9% (74.2, 93.6) and 81.0% (65.8, 89.9). In squamous NSCLC, median PFS was 7.3 (3.7, NE), 3, 6 and 9-month PFS rate (95% CI) was 80.0% (54.9, 92.0), 55.9% (27.0, 77.2) and 46.6% (19.0, 70.3), 3, 6 and 9-month OS rate (95% CI) were 100.0% (100.0,100.0), 88.2% (60.2, 96.9) and 88.2% (60.2, 96.9).
Conclusion
The bispecific antibody, KN046 was well tolerated and effective as 2nd line treatment of advanced NSCLC. KN046 showed promising PFS and OS benefit in squamous NSCLC.
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P79 - Immunotherapy (Phase II/III Trials) - Immunotherapy Plus Chemotherapy (ID 256)
- Event: WCLC 2020
- Type: Posters
- Track: Immunotherapy (Phase II/III Trials)
- Presentations: 2
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P79.02 - Updated OS and Time to Second Progression with First-Line Camrelizumab Plus Chemo vs Chemo for Advanced Non-Squamous NSCLC (ID 1732)
00:00 - 00:00 | Author(s): Jian Fang
- Abstract
Introduction
At the pre-specified interim analysis of the CameL phase 3 study, camrelizumab plus chemo (carboplatin + pemetrexed) as first-line therapy significantly improved the PFS compared with chemo alone and showed acceptable safety profile in patients with advanced non-squamous NSCLC without sensitizing EGFR and ALK alterations (2019 WCLC OA04.03). Herein, we provide an update on OS and PFS2 (time to second progression) based on long-term follow-up.
Methods
Eligible patients were randomized 1:1 to receive 4 to 6 cycles of chemo with (n=205) or without (n=207) camrelizumab, followed by pemetrexed with or without camrelizumab as maintenance therapy. Crossover to camrelizumab monotherapy was permitted for patients in the chemo alone group who had radiological disease progression. Data on post-study anticancer therapy and outcomes were collected. PFS2 was defined as time from randomization to disease progression after the first disease progression event or death, whichever occurred first. There was no multiplicity adjustment, and nominal one-sided P values are presented. ClinicalTrials.gov number: NCT03134872.
Results
At data cutoff on February 25, 2020, the median follow-up duration was 19.3 months (IQR 9.8−23.7). 35 (17.1%) patients in the camrelizumab plus chemo group and 18 (8.7%) in the chemo alone group were still receiving the assigned first-line study treatment. Camrelizumab plus chemo prolonged median overall survival, as compared with chemo alone (27.9 months [95% CI 21.9−not reached] vs 20.5 months [95% CI 15.9−24.4]; HR 0.73 [95% CI 0.55−0.96]; P=0.0117). Second-line or later therapy was received by 98 (47.8%) patients in the camrelizumab plus chemo group and 135 (65.2%) patients in the chemo alone group. Median PFS2 was 18.9 months (95% CI 15.7−21.2) vs 12.5 months (95% CI 10.6−15.6) in patients who received vs did not receive first-line camrelizumab (HR 0.66 [95% CI 0.52−0.84]; P=0.0004). Benefits in OS and PFS2 with camrelizumab plus chemo were also found in patients with PD-L1 TPS ≥1% (Table). The safety profile was consistent with the previous report at interim analysis.
Table.
ConclusionOS
PFS2
No. events/No. patients
HR (95% CI)
P value
No. events/No. patients
HR (95% CI)
P value
Camrelizumab plus chemo
Chemo alone
Camrelizumab plus chemo
Chemo alone
All patients (n=412)
44.9%
54.6%
0.73 (0.55−0.96)
0.0117
60.0%
71.5%
0.66 (0.52−0.84)
0.0004
Patients with PD-L1 TPS ≥1% (n=255)
38.4%
49.6%
0.70 (0.48−1.02)
0.0318
53.6%
67.5%
0.64 (0.46−0.88)
0.0027
Camrelizumab plus carboplatin and pemetrexed as first-line therapy showed long-term benefit in OS and PFS2 compared with chemo alone in Chinese patients with advanced non-squamous NSCLC without EGFR and ALK alterations, despite 48.3% of patients in the chemo alone group receiving subsequent immunotherapy. No new safety signal was observed. This combination represents a potential standard first-line therapy for these patients.
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P79.08 - Sintilimab ± IBI305 Plus Chemotherapy for Patients With EGFR-Mutant Non-Squamous NSCLC Failed to EGFR-TKI Treatment (ID 1304)
00:00 - 00:00 | Author(s): Jian Fang
- Abstract
Introduction
The standard treatment for advanced non-squamous non-small cell lung cancer (nsqNSCLC) patients with EGFR-mutation is osimertinib or other recommended tyrosine kinase inhibitors (TKIs). For those who failed to TKI treatment, the choice of systemic treatment is limited, including platinum-based chemotherapy, and new therapy regimens are needed to improve the efficacy. T-cell mediated cancer cell killing of anti-PD-1 antibody may be enhanced through reversal of vascular endothelial growth factor (VEGF)-mediated immunosuppression. Sintilimab is a humanized, monoclonal antibody that blocks the interaction between PD-1 and its ligands. IBI305 is a biosimilar candidate for bevacizumab which is a monoclonal antibody against VEGF. ORIENT-31 study is a randomized, double-blind, multi-center, phase 3 study to compare the efficacy and safety of sintilimab with or without IBI305 plus pemetrexed and cisplatin versus placebo plus pemetrexed and cisplatin. (NCT03802240).
Methods
Patients, who have failed to epidermal growth factor receptor (EGFR)-TKI treatment, with histologically/cytologically confirmed Stage IIIB-IV nsqNSCLC with EGFR mutations will be enrolled in this two-stage study. The total planned sample size is 600, with 480 patients in the common enrollment stage and 120 patients in the extension enrollment stage. In the common enrollment stage, 480 patients will be enrolled and randomized (1:1:1) into Group A (sintilimab + IBI305 + pemetrexed + cisplatin), Group B (sintilimab + placebo 2 + pemetrexed + cisplatin) and Group C (placebo 1 + placebo 2 + pemetrexed + cisplatin). In the extension enrollment stage, 120 patients will be enrolled and randomized (1:1) into Group A and Group B. Stratification factors include gender (male or female) and brain metastasis (with or without). Sintilimab 200 mg with or without IBI305 15 mg/kg will be administrated every 3 weeks (Q3W) until disease progression, unacceptable toxicity or voluntary patient withdrawal for up to 24 months. The pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 will be administrated Q3W for up to 4 cycles. The primary efficacy endpoint is progression-free survival per RECIST V 1.1 by Independent Radiographic Review Committee. The secondary efficacy endpoints include overall survival, objective response rate, disease control rate, time to response and duration of response per RECIST V1.1. By March 9, 2020, 112 patients have been enrolled in this study.
