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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
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
- Moderators:
- Coordinates: 1/28/2021, 07:00 - 09:00, Scientific Program Auditorium
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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
- Presentation
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
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
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.