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Ke Wang



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    FP14 - Targeted Therapy - Clinically Focused (ID 252)

    • Event: WCLC 2020
    • Type: Posters (Featured)
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      FP14.17 - Efficacy and Safety of Pralsetinib in Chinese Patients with Advanced RET Fusion+ Non-Small Cell Lung Cancer after Platinum-Based Chemotherapy (ID 2954)

      00:00 - 00:00  |  Author(s): Ke Wang

      • Abstract
      • Slides

      Introduction

      RET fusions have been reported as oncogenic drivers in 1% to 2% of non-small cell lung cancer (NSCLC) patients. Pralsetinib is a highly potent and selective RET kinase inhibitor targeting oncogenic RET alterations. A global phase I/II ARROW study (NCT03037385) has demonstrated broad and durable antitumor activity of pralsetinib in a variety of advanced RET-altered solid tumors. Here we present the efficacy and safety results from the phase II NSCLC extension group that enrolled patients from China sites.

      Methods

      RET fusion+ Chinese NSCLC patients previously treated with platinum-based chemotherapy were enrolled and dosed with pralsetinib 400 mg QD. The primary objectives were to assess the objective response rate (ORR) by blinded independent central review (BICR) per RECIST v1.1 and safety profile in Chinese patients.

      Results

      From Aug to Dec 2019, a total of 37 patients were enrolled; most (94.6%) of the patients had ECOG PS of 1 and about half (48.6%) had received ≥3 prior systemic regimens. As of the data cut-off (22 May 2020), 28 patients remained on study treatment and 9 discontinued from pralsetinib (4 due to disease progression and 3 due to adverse events). The median treatment duration was 6.1 (range: 0.9-9.4) months. In 32 evaluable patients who had measurable disease at baseline per BICR, the ORR was 56.3% (95% CI: 37.7, 73.6) (1 complete response [CR] and 17 partial responses [PR]); in addition, 2 patients achieved PR pending confirmation. Clinical benefit rate (defined as the rate of confirmed CR or PR, or stable disease lasting ≥ 16 weeks from the first dose) was 81.3% (95% CI: 63.6, 92.8). Disease control rate was 96.9% (95% CI: 83.8, 99.9), and tumor regression was observed in all 13 patients with stable disease. The median time to response was 1.9 (range: 1.7-5.5) months. Median duration of response (DOR) was not reached; 6-month DOR rate was 83.1% (95% CI: 61.5, 100). All 37 patients experienced at least one treatment emergent adverse event (TEAE). The most frequently reported TEAEs were aspartate aminotransferase increased (83.8%), neutrophil count decreased (70.3%), anaemia (67.6%), white blood cell count decreased (56.8%), and hypertension (51.4%). Grade ≥ 3 TEAEs occurred in 25 (67.6%) patients, with the most common being neutrophil count decreased (24.3%), anaemia (24.3%), hypertension (16.2%), hypophosphataemia (13.5%), platelet count decreased (10.8%) and hypokalaemia (10.8%). There were no pralsetinib related AEs leading to death.

      Conclusion

      This is the first pivotal study to show that pralsetinib has deep and durable antitumor activity, and is well-tolerated in a cohort of Chinese patients with RET fusion+ NSCLC previously treated with platinum-based chemotherapy. The data are consistent with previously reported data from the global population in the ARROW trial. Overall, pralsetinib demonstrated a favorable benefit-risk profile, potentially offering a transformative medicine to Chinese RET-fusion driven advanced NSCLC patients.

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    JICC01 - Joint IASLC-CAALC-CSCO Session: The Truth and Myth of Oral Anti-VEGFR Inhibitors for Advance NSCLC (ID 276)

    • Event: WCLC 2020
    • Type: Workshop
    • Track: N.A.
    • Presentations: 1
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      JICC01.14 - Efficacy and Safety of Pralsetinib in Chinese Patients with Advanced RET Fusion+ Non-Small Cell Lung Cancer after Platinum-Based Chemotherapy (ID 4273)

      07:00 - 09:00  |  Author(s): Ke Wang

      • Abstract

      Introduction
      RET fusions have been reported as oncogenic drivers in 1% to 2% of non-small cell lung cancer (NSCLC) patients. Pralsetinib is a highly potent and selective RET kinase inhibitor targeting oncogenic RET alterations. A global phase I/II ARROW study (NCT03037385) has demonstrated broad and durable antitumor activity of pralsetinib in a variety of advanced RET-altered solid tumors. Here we present the efficacy and safety results from the phase II NSCLC extension group that enrolled patients from China sites. Methods
      RET fusion+ Chinese NSCLC patients previously treated with platinum-based chemotherapy were enrolled and dosed with pralsetinib 400 mg QD. The primary objectives were to assess the objective response rate (ORR) by blinded independent central review (BICR) per RECIST v1.1 and safety profile in Chinese patients. Results

      From Aug to Dec 2019, a total of 37 patients were enrolled; most (94.6%) of the patients had ECOG PS of 1 and about half (48.6%) had received ≥3 prior systemic regimens. As of the data cut-off (22 May 2020), 28 patients remained on study treatment and 9 discontinued from pralsetinib (4 due to disease progression and 3 due to adverse events). The median treatment duration was 6.1 (range: 0.9-9.4) months. In 32 evaluable patients who had measurable disease at baseline per BICR, the ORR was 56.3% (95% CI: 37.7, 73.6) (1 complete response [CR] and 17 partial responses [PR]); in addition, 2 patients achieved PR pending confirmation. Clinical benefit rate (defined as the rate of confirmed CR or PR, or stable disease lasting ≥ 16 weeks from the first dose) was 81.3% (95% CI: 63.6, 92.8). Disease control rate was 96.9% (95% CI: 83.8, 99.9), and tumor regression was observed in all 13 patients with stable disease. The median time to response was 1.9 (range: 1.7-5.5) months. Median duration of response (DOR) was not reached; 6-month DOR rate was 83.1% (95% CI: 61.5, 100). All 37 patients experienced at least one treatment emergent adverse event (TEAE). The most frequently reported TEAEs were aspartate aminotransferase increased (83.8%), neutrophil count decreased (70.3%), anaemia (67.6%), white blood cell count decreased (56.8%), and hypertension (51.4%). Grade ≥ 3 TEAEs occurred in 25 (67.6%) patients, with the most common being neutrophil count decreased (24.3%), anaemia (24.3%), hypertension (16.2%), hypophosphataemia (13.5%), platelet count decreased (10.8%) and hypokalaemia (10.8%). There were no pralsetinib related AEs leading to death.

      Conclusion

      This is the first pivotal study to show that pralsetinib has deep and durable antitumor activity, and is well-tolerated in a cohort of Chinese patients with RET fusion+ NSCLC previously treated with platinum-based chemotherapy. The data are consistent with previously reported data from the global population in the ARROW trial. Overall, pralsetinib demonstrated a favorable benefit-risk profile, potentially offering a transformative medicine to Chinese RET-fusion driven advanced NSCLC patients.

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    P84 - Targeted Therapy - Clinically Focused - ALK (ID 261)

    • 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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      P84.07 - Distribution and Therapeutic Outcomes of Intergenic Sequence-ALK Fusion and Coexisting ALK Fusions in Lung Adenocarcinoma Patients (ID 1066)

      00:00 - 00:00  |  Author(s): Ke Wang

      • Abstract
      • Slides

      Introduction

      ALK-rearranged NSCLC patients show survival benefits from ALK inhibitor. Studies about outcome were mostly focused on EML4–ALK fusion. Here, we performed next-generation sequencing (NGS) of baseline specimens from ALK-positive patients to examine the rearrangement distribution and possible correlation to therapeutic benefit.

      Methods

      ALK-positive NSCLC patient(determined by immunohistochemistry) were screened at the West China Hospital, and NGS was performed on baseline samples. Clinical information and therapeutic outcomes were collected and retrospectively analyzed.

      Results

      Among the 89 patients with 22 ALK rearrangements partners, fusions of intergenic sequences with ALK were found in 15 (16.85%). Non-EML4–ALK fusions were present in 18 patients (20.22%), while EML4–ALK fusions in 71 (79.76%). Coexisting rearrangements were present in 16 patients (17.98%). Intergenic–ALK and non EML4–ALK fusions occurred at higher rates in patients with coexisting fusions (62.5% versus 6.85%, and 62.5% versus 10.96%). First-line crizotinib was administered in 41 patients, and the median progression-free survival (mPFS) was 9.7 months. No significant difference in mPFS was found between patients with or without intergenic ALK fusion (12 versus 9.6 months, p = 0.989). In the seven patients who had at least two fusions each, the mPFS was 11.9 months, compared with 9 months among the 24 patients with single (p = 0.336). No significant difference in mPFS was observed between patients with and without EML4–ALK fusions (9.6 versus 12 months, p = 0.924). The hazard ratio(HR) of gender, age and three rearrangements (EML4-, non EML4-, intergenic-ALK) were 0.47, 1.18, 1.09, 1.31, 0.96, respectively.

      Table 1 Characteristics of enrolled patients.

      Characteristic

      Total

      (n = 90)

      Treatment

      P value

      Surgery

      (n = 46)

      Systemic therapy

      (n = 44)

      Age (median [range], years)

      51 (29-78)

      52.5 (30-78)

      49 (29-70)

      0.396

      Gender (cases, %)

      0.404

      Male

      47 (52.2)

      26 (56.5)

      21 (47.7)

      Female

      43 (47.8)

      20 (43.5)

      23 (52.3)

      Smoking status (cases, %)

      0.185

      Smoker

      6 (6.7)

      1 (2.2)

      5 (11.4)

      Non-smoker

      84 (93.3)

      45 (97.8)

      39 (88.6)

      Histology (cases, %)

      /

      Adenocarcinoma

      90 (100)

      46 (100)

      44 (100)

      Non-adenocarcinoma

      0 (0)

      0 (0)

      0 (0)

      ECOG performance status (cases, %)

      0.689

      0-1

      79 (87.8)

      41 (89.1)

      38(86.4)

      2-4

      11 (12.2)

      5 (10.9)

      6 (13.6)

      Stage (cases, %)

      <0.001

      I-III

      49 (54.4)

      46 (100)

      3 (6.8)

      IV

      41 (45.6)

      0 (0)

      41 (93.2)

      Metastasis (cases, %)

      <0.001

      Absent

      49 (54.4)

      46 (100)

      3 (6.8)

      Present

      41 (45.6)

      0 (0)

      41 (93.2)

      Brain metastasis

      13 (14.4)

      0 (0)

      13 (29.5)

      Bone metastasis

      24 (26.7)

      0 (0)

      24 (54.5)

      Multi-organ metastases

      20 (22.2)

      0 (0)

      20 (45.5)

      ALK aberrations (cases, %)

      0.489

      Rearrangement free Uncertain aberration

      1 (1.1)

      0 (0)

      1 (2.3)

      ALK rearrangement

      89 (98.9)

      46 (100)

      43 (97.7)

      Distribution of rearrangements (cases, %)

      Intergenic sequence-ALK fusion

      15 (16.9)

      9 (19.6)

      6 (14.0)

      0.480

      Non-EML4-ALK fusion

      18 (20.2)

      10 (21.7)

      8 (18.6)

      0.713

      EML4-ALK fusion

      Variant 1

      26 (29.2)

      12 (26.1)

      14 (32.6)

      0.502

      Variant 2

      4 (4.5)

      3 (6.5)

      1 (2.3)

      0.658

      Variant 3

      30 (33.7)

      14 (30.4)

      16 (37.2)

      0.499

      Other variants

      11 (12.4)

      8 (17.4)

      3 (7.0)

      0.136

      Status of coexisting ALK fusions (cases, %)

      Absent

      73 (82.0)

      37 (80.4)

      36 (83.7)

      0.687

      Intergenic sequence-ALK fusion alone

      5 (5.6)

      2 (4.3)

      3 (7.0)

      0.938

      Non-EML4-ALK fusion alone

      8 (9.0)

      5 (10.9)

      3 (7.0)

      0.787

      EML4-ALK fusion alone

      60 (67.4)

      30 (65.2)

      30 (69.8)

      0.647

      Present

      16 (18.0)

      9 (19.6)

      7 (16.3)

      0.687

      Intergenic sequence-ALK fusion + EML4-ALK fusion

      6 (6.7)

      4 (8.7)

      2 (4.7)

      0.736

      Intergenic sequence-ALK fusion + non-EML4-ALK fusion

      1 (1.1)

      1 (2.2)

      0 (0)

      1.000

      EML4-ALK fusion + non-EML4-ALK fusion

      3 (3.4)

      1 (2.2)

      2 (4.7)

      0.953

      Intergenic-ALK fusion + EML4-ALK fusion+ non-EML4-ALK fusion

      2 (2.2)

      2 (4.3)

      0 (0)

      0.495

      Intergenic-ALK fusion + intragenic-ALK fusion + non-EML4-ALK fusion

      1 (1.1)

      0 (0)

      1 (2.3)

      0.483

      non-EML4-ALK fusion + non-EML4-ALK fusion

      3 (3.4)

      1 (2.2)

      2 (4.7)

      0.953

      Table 2 Multivariate Cox Analysis

      111.png

      Conclusion

      This is the first to report the occurrence rates and distribution of intergenic–ALK and coexisting of ALK fusions. Intergenic–ALK and non-EML4–ALK were more likely to coexist with other fusions. Neither the type nor number of rearrangements had a significant effect on the therapeutic benefit of treatment with crizotinib.

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