150P A phase I study of TQ-B2450, a PD-L1 mAb, plus anlotinib in EGFR+ advanced NSCLC patients failed to prior EGFR TKI therapies

8072 Background: A phase I study ofnivolumab (a PD-1 receptor blocking Ab) demonstrated durable responses and a tolerable safety profile in NSCLC pts who failed ≥1 chemotherapy regimen. We report an interim analysis of a phase I study with nivolumab + PT-doublets in chemotherapy-naive advanced NSCLC pts. Methods: Stage IIIB/IV NSCLC pts were randomized by histology ≥9 wk prior to data lock (Dec 2012) to: A) nivolumab/gemcitabine/cisplatin; B) nivolumab/pemetrexed/cisplatin; or C) nivolumab/carboplatin/paclitaxel according to a phase I dose de-escalation design to assess the toxicities and incidence of DLTs in the first 6 wk of dosing. Nivolumab doses were started at 10 mg/kg IV Q3W and given until progression. PT-doublet was given for 4 cycles at standard dosing. At a tolerable dose, cohorts were expanded up to 20 pts. Results: 43 pts were treated with nivolumab + PT-doublet: Arm A, n=12 squamous (sq); Arm B, n=15 (non-sq); and Arm C, n=16 (3 sq + 13 non-sq). No DLTs were seen across arms. Gr 3-4 regimen-related AEs were 49% across arms, and 25%, 47%, and 69% for Arms A, B, and C, respectively. Select Gr 3-4 toxicities reported included: pneumonitis, rash, nephritis, and colitis (Table). 3 pts had Gr 3 pneumonitis and were addressed with management algorithms (dose discontinuation and immune-modulating therapies). 2 pts fully resolved, however 1 resolved pt subsequently died from Aspergillus pneumonia. 1 pt died of disease progression with unresolved pneumonitis (autopsy confirmed). Total/Confirmed ORRs (RECIST 1.1) were 43/33%, 40/33%, and 31/31% in Arms A, B, and C, respectively. Conclusions: No DLTs were seen with 10 mg/kg nivolumab combined with PT-doublets; maintenance treatment is ongoing. Similar to monotherapy, select nivolumab related toxicities can be addressed with management algorithms. Safety, durability, and confirmation of responses will be updated based on a 2013 data analysis, including a 5 mg/kg nivolumab dose cohort. Clinical trial information: NCT01454102. [Table: see text]

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A phase I study to evaluate safety, tolerability, pharmacokinetics and antineoplastic activity of BPI-7711 in patients with EGFR/T790M mutation advanced or recurrent NSCLC.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.9034 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 9034-9034 ◽

Cited By ~ 1

Author(s):

Yuankai Shi ◽

Jian Fang ◽

Yongqian Shu ◽

Donglin Wang ◽

Huiqing Yu ◽

...

Keyword(s):

Phase I ◽

Disease Progression ◽

Dose Escalation ◽

Phase I Study ◽

Daily Treatment ◽

Upper Respiratory Tract ◽

Phase Ii Trials ◽

T790m Mutation ◽

Nsclc Patients ◽

Egfr Tki

9034 Background: BPI-7711 is a 3rd generation irreversible EGFR-TKI that is selectively against EGFR TKI–sensitizing mutations and the T790M resistance mutations. We are conducting a phase I study to determine the safety and efficacy of BPI-7711 in patients with advanced or recurrent EGFRm+/T790M+ NSCLC. Methods: NSCLC patients who had documented disease progression after 1st/2nd generation EGFR-TKI treatment and with EGFRm+/T790M+ confirmed by central lab were enrolled in the multicenter trial (NCT03386955) into “3+3” dose escalation or expansion cohorts. BPI-7711 was orally administered at doses of 30~240 mg in capsules. Patients in dose-escalation cohorts firstly received a single dose of BPI-7711 followed by a 7-day pharmacokinetic (PK) evaluation period then received the same dose daily until disease progression or intolerable toxicity(ies) per CTCAE V4.03. Treatment efficacy per RECIST 1.1 was evaluated every 6 weeks since daily treatment commence. Once efficacy was observed in a dose, its expansion cohort was opened to enroll patients for daily treatment. Results: As of 23 December 2018, 82 patients (median age 55, 27 males, 55 females) were enrolled into 5 dose escalation cohorts (30/60/120/180/240 mg) and 4 dose expansion cohorts (30/60/120/180 mg). No DLT was observed and MTD was not reached. For all safety-evaluable patients, most common treatment emergent adverse events (TEAEs) (≥10%) were white blood cell count decreased (21.3%), neutrophil count decreased (17.3%), upper respiratory tract infection (17.3%), vomiting (12.0%) and diarrhea (10.7%), and all were Grade 1 or 2. Grade 3~4 TEAEs were occurred in 8.0% patients and 4.0% of them were treatment-related per investigators’ judgement. SAEs were reported in 4.0% of patients, and 1.3% were treatment-related. For all efficacy-evaluable patients, the overall ORR of all doses was 54.5% (30/55) including 1.8% CR and 52.7% PR. The disease control rate (DCR) was 96.4%. For patients in 120/180 mg cohorts, the ORR was 64.1% (25/39) and DCR was 97.4%. PK analyses showed BPI-7711 exposure increased in a dose-proportional manner from 30 to 180 mg after single and multiple doses. Conclusions: BPI-7711 was well tolerated and highly effective in acquired T790M+ NSCLC patients. Phase II trials are under preparation. Clinical trial information: NCT03386955.

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A Phase I Study of AZD9291 in Patients with Egfr-Tki-Resistant Advanced Nsclc – Updated Progression Free Survival and Duration of Response Data

Annals of Oncology ◽

10.1093/annonc/mdv128.05 ◽

2015 ◽

Vol 26 ◽

pp. i57 ◽

Cited By ~ 13

Author(s):

P.A. Jänne ◽

M.-J. Ahn ◽

D.-W. Kim ◽

S.-W. Kim ◽

D. Planchard ◽

...

Keyword(s):

Phase I ◽

Phase I Study ◽

Advanced Nsclc ◽

Progression Free Survival ◽

Free Survival ◽

Response Data ◽

Duration Of Response ◽

Egfr Tki

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Anlotinib Hydrochloride Combined With EGFR-Tyrosine Kinase Inhibitor (TKI) in Treating Advanced NSCLC Patients With Acquired Resistance to EGFR-TKI

Case Medical Research ◽

10.31525/ct1-nct04007835 ◽

2019 ◽

Author(s):

Keyword(s):

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitor ◽

Advanced Nsclc ◽

Kinase Inhibitor ◽

Acquired Resistance ◽

Egfr Tyrosine Kinase Inhibitor ◽

Egfr Tyrosine Kinase ◽

Nsclc Patients ◽

Egfr Tki

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P19.01 Local Ablative Radiotherapy on Oligo-Progression while Continued on EGFR-TKI in Advanced NSCLC Patients: A Longer Cohort

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2021.01.562 ◽

2021 ◽

Vol 16 (3) ◽

pp. S355

Author(s):

F.S.T. Mok ◽

M. Tong ◽

H. Loong ◽

T. Mok

Keyword(s):

Advanced Nsclc ◽

Nsclc Patients ◽

Egfr Tki

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SELECT-3: a phase I study of selumetinib in combination with platinum-doublet chemotherapy for advanced NSCLC in the first-line setting

British Journal of Cancer ◽

10.1038/bjc.2017.271 ◽

2017 ◽

Vol 117 (7) ◽

pp. 938-946 ◽

Cited By ~ 7

Author(s):

Alastair Greystoke ◽

Nicola Steele ◽

Hendrik-Tobias Arkenau ◽

Fiona Blackhall ◽

Noor Md Haris ◽

...

Keyword(s):

Phase I ◽

Phase I Study ◽

Advanced Nsclc ◽

First Line ◽

Line Setting ◽

Doublet Chemotherapy ◽

Platinum Doublet

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Efficacy and Acquired Resistance of EGFR-TKI Combined with Chemotherapy as First-Line Treatment for Chinese Patients with Advanced Non-Small Cell Lung Cancer in a Real-world Setting

10.21203/rs.3.rs-121107/v1 ◽

2020 ◽

Author(s):

Qianqian Wang ◽

Wen Gao ◽

Fangyan Gao ◽

Shidai Jin ◽

Tianyu Qu ◽

...

Keyword(s):

Egfr Mutation ◽

Advanced Nsclc ◽

Acquired Resistance ◽

Small Cell ◽

Combination Group ◽

Monotherapy Group ◽

Small Cell Lung ◽

T790m Mutation ◽

Nsclc Patients ◽

Egfr Tki

Abstract Background To compare the benefits and explore the cause of acquired resistance of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and its combination with chemotherapy in advanced non-small-cell lung cancer (NSCLC) patients harboring EGFR mutation in a real-life setting.Methods This retrospective analysis included 117 advanced NSCLC patients with EGFR mutation who underwent next-generation sequencing (NGS) prior to treatment. The combination group included 50 patients who received the regimen of EGFR-TKI combined with chemotherapy, while the EGFR-TKI monotherapy group included 67 patients treated with TKI only. The primary endpoint of this study was progression-free survival (PFS); the secondary endpoints were overall survival (OS), response rate, and toxicity.Results The median PFS was significantly longer in the combination group than in the EGFR-TKI monotherapy group (19.00 months [95% CI, 14.674-23.326] vs. 11.70 months [95% CI, 10.807-12.593], p = 0.000). Subgroup analysis showed a similar trend of results. The median OS was not reached in the combination group and was 38.50 (95% CI, 35.300-41.700) months in the EGFR-TKI monotherapy group (p = 0.586). Patients in the combination group were more likely to experience adverse events, most of which showed the severity of grade 1 or 2. T790M mutation remains the main reason for acquired resistance, and the frequency of T790M mutation was similar between the two groups (p = 0.898). Conclusions Compared with EGFR-TKI monotherapy, EGFR-TKI combined with chemotherapy significantly improved PFS in advanced NSCLC patients with EGFR mutation, with acceptable toxicity.

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