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Jay M. Lee
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MA03 - New and Revisited Prognostic Factors in Early Stage Lung Cancer (ID 119)
- Event: WCLC 2020
- Type: Mini Oral
- Track: Early Stage/Localized Disease
- Presentations: 1
- Moderators:
- Coordinates: 1/29/2021, 15:30 - 16:30, Scientific Program Auditorium
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MA03.12 - Discussant (ID 4185)
15:30 - 16:30 | Presenting Author(s): Jay M. Lee
- Abstract
- Presentation
Abstract not provided
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OA06 - Updates on EGFR Targeted Perioperative Therapy and Precision Adjuvant Chemotherapy (ID 118)
- Event: WCLC 2020
- Type: Oral
- Track: Early Stage/Localized Disease
- Presentations: 1
- Moderators:
- Coordinates: 1/29/2021, 16:45 - 17:45, Scientific Program Auditorium
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OA06.06 - Clinical/Biomarker Data for Neoadjuvant Atezolizumab in Resectable Stage IB-IIIB NSCLC: Primary Analysis in the LCMC3 Study (ID 3256)
16:45 - 17:45 | Author(s): Jay M. Lee
- Abstract
- Presentation
Introduction
Neoadjuvant immune checkpoint inhibitor therapies are well tolerated and may be of benefit in early-stage non-small cell lung cancer (NSCLC). Here we report clinical and biomarker data from the Phase II LCMC3 (NCT02927301) study evaluating pre-operative treatment with atezolizumab (anti-PD-L1) in patients with untreated stage IB to IIIB resectable NSCLC.
Methods
Patients had clinical stage IB-IIIB resectable NSCLC and ECOG 0/1. Patients received neoadjuvant atezolizumab 1200 mg intravenously every 3 weeks for ≤2 cycles followed by surgical resection (day 40±10). Those with clinical benefit could continue adjuvant atezolizumab for ≤12 months. The primary endpoint was major pathological response (MPR; ≤10% viable tumor cells) at surgery in patients without known EGFR/ALK mutations. Secondary endpoints included MPR by PD-L1 status, tumor mutation burden (TMB), and adverse events (AEs), including treatment-related (TRAE) and immune-related (irAE). Biomarker analyses included multiplex immunofluorescence (mIF) image analysis, whole exome sequencing, RNA sequencing and multi-parameter flow cytometry.
Results
The study included 181 NSCLC patients, of whom 159 had surgery (Table). In patients without known EGFR/ALK alterations, 30/147 (20.4% [95% CI: 14%-28%]) achieved MPR and 10/147 (6.8% [95% CI: 3%-12%]) achieved pathological complete response. The pre-surgery ORR (RECISTv1.1) was 7% (11/159), all partial responses. 143 (90%) patients had stable disease and 4 (3%) had progressive disease (missing RECIST assessment, n=1). AEs occurred in 178/181 (98%) patients, including AEs leading to discontinuation of treatment in 15/181 (8%), TRAEs in 122/181 (67%) and irAEs in 75/181 (41%). MPR was associated with PD-L1 status (clone 22C3), with 16% MPR in TPS<1% and 29% in TPS≥1% (P=0.117); MPR was 14% in TPS<50% and 37% in TPS≥50% (P=0.009). mIF showed that treatment increased the ratio of CD3+/CD8+ and GZMB+/CD8+ T-cells to CD3+/FOXP3+ cells in both tumor (n=45) and stromal (n=44) compartments, suggesting a shift toward T-cell activation. MPR was not observed in patients with known EGFR mutations (n=7; 1 additional patient did not have surgery) or ALK fusions (n=5). Median TMB was 7.2 mutations/Mb (range, 0.8-43.5) (n=53), and patients with higher TMB trended toward better pathological response. STK11/LKB1 and KEAP1 mutations were more frequent in non-MPR patients (Table). Biomarker analyses are ongoing.
Conclusion
The trial met its primary endpoint of 20% MPR with neoadjuvant atezolizumab in patients with resectable stage IB-IIIB NSCLC. Data suggest MPR was positively associated with PD-L1 expression and negatively associated with EGFR/ALK alterations. Ongoing comprehensive analyses of biomarker data will provide insights into mechanisms of immunotherapy in lung cancers.
Baseline characteristics
Underwent surgery
No surgery
(N = 22)Enrolled and dosed NSCLC patients
(N = 181)Achieved MPR
(N = 30)No MPR or MPR not determined
(N = 129)Median age (range), y
67 (39-83)
65 (37-82)
68 (46-81)
65 (37-83)
Female, n (%)
23 (77)
56 (43)
14 (64)
93 (51)
Race, n (%)
White
24 (80)
105 (83)
16 (73)
145 (81)
Black or African American
3 (10)
7 (6)
3 (14)
13 (7)
Asian
1 (3)
7 (6)
1 (5)
9 (5)
Unknown
2 (7)
8 (6)
2 (9)
12 (7)
Squamous histology, n (%)
14 (47)
45 (35)
10 (46)
69 (38)
Clinical stage, n (%)
IB
3 (10)
12 (9)
1 (5)
16 (9)
IIA
3 (10)
16 (12)
1 (5)
20 (11)
IIB
9 (30)
43 (33)
8 (36)
60 (33)
IIIA
12 (40)
49 (38)
10 (46)
72 (39)
IIIB
3 (10)
9 (7)
2 (9)
14 (8)
Tobacco use, n (%)
Current
12 (40)
16 (12)
7 (32)
35 (19)
Former
16 (53)
99 (77)
13 (59)
128 (71)
Never
2 (7)
14 (11)
2 (9)
18 (10)
TPS at screening, n (%)
≥ 50
13 (43)
25 (19)
2 (9)
40 (22)
≥ 1 to < 50
1 (3)
16 (12)
1 (5)
18 (10)
< 1
7 (23)
43 (33)
8 (36)
58 (32)
Unknowna
9 (30)
45 (35)
11 (50)
65 (36)
STK11/LKB1 mutation, n (%)b
No
17 (57)
54 (41)
3 (14)
74 (41)
Yes
1 (3)
8 (6)
0 (0)
9 (5)
Unknowna
12 (40)
67 (52)
19 (86)
98 (54)
KEAP1 mutation, n (%)b
No
16 (53)
55 (43)
3 (14)
74 (41)
Yes
2 (7)
7 (5)
0 (0)
9 (5)
Unknowna
12 (40)
67 (52)
19 (86)
98 (54)
Safety
All
Grade 3-4
Grade 5
Any AE, n (%)
178 (98)
75 (41)
6 (3)
AE leading to treatment discontinuation, n (%)
15 (8)
10 (6)
1 (1)
TRAE, n (%)
122 (67)
29 (16)
1 (1)
irAE, n (%)
75 (41)
16 (9)
1 (1)
TPS, tumor proportion score; measured with PD-L1 immunohistochemical 22C3 assay.
a Analysis ongoing at time of abstract preparation. b In these groups, 3 patients had dual STK11/LKB1 and KEAP1 mutations. None achieved MPR.
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P03 - Early Stage/Localized Disease - Clinical Trials in Progress (ID 112)
- Event: WCLC 2020
- Type: Posters
- Track: Early Stage/Localized Disease
- Presentations: 2
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P03.04 - Phase II Study of TKIs as Neo(adjuvant) Therapy in Stage II–III Resectable NSCLC with ALK, ROS1, NTRK or BRAFV600 Alterations (ID 1802)
00:00 - 00:00 | Presenting Author(s): Jay M. Lee
- Abstract
Introduction
Despite complete surgical resection, cure rates remain unacceptable in early-stage NSCLC. Trials of neoadjuvant and adjuvant chemotherapy have demonstrated a 5-year overall survival benefit of 5% for patients with resectable disease. Developing new treatment strategies to increase cures following resection is critical in this patient population. There are numerous immunotherapy trials ongoing in the neoadjuvant and adjuvant setting for patients with early-stage NSCLC. While there are a few targeted therapy trials in the adjuvant setting for patients with genetic alterations, neoadjuvant targeted therapies have remained incompletely explored in patients with potentially resectable NSCLC. Neoadjuvant trials allow for early trial read outs and in vivo efficacy assessment, which can guide adjuvant therapy options. The use of targeted therapies in patients with early-stage lung cancers with driver mutations has the potential to improve outcomes and provide an alternative treatment modality beyond immunotherapy and chemotherapy. Tyrosine kinase inhibitors (TKIs) are hypothesized to provide greater clinical benefit with a more favorable safety profile than the current standard of care platinum-based chemotherapy in the neoadjuvant setting. This ongoing Phase II umbrella study (ML41591) is designed to determine the efficacy and safety of targeted therapies for patients with stage II–III NSCLC with ALK, ROS1, NTRK or BRAFV600 alterations.
Methods
ML41591 is a Phase II, multicenter, non-randomized, open-label, umbrella study in patients with resectable stage II, IIIA, or selected IIIB NSCLC tumors that harbor fusions in ALK, ROS1, NTRK or BRAFV600 missense mutation. The study is designed to determine the efficacy and safety of targeted therapies, and to investigate potential surrogate biomarkers of response. Patients will be enrolled and assigned to treatment within the appropriate cohort:
- ALK cohort: ALK gene rearrangements - alectinib
- ROS1 cohort: ROS1 gene rearrangements - entrectinib
- NTRK cohort: NTRK1/2/3 gene rearrangements - entrectinib
- BRAF cohort: BRAFV600 mutation - vemurafenib plus cobimetinib.
Each cohort will enroll approximately 25 patients. The study will be conducted in two parts: pre-surgery neoadjuvant treatment will evaluate pathologic response to neoadjuvant TKIs in each cohort. Patients who undergo surgery and whose tumors lack radiographic progression will enter the post-surgery surveillance phase, which includes adjuvant treatment and follow-up for survival. This portion of the trial is exploratory. Patients will receive 4 cycles of chemotherapy followed by TKIs as adjuvant therapy for up to 24 months. The primary efficacy objective for this study is to evaluate the major pathological response rate for each treatment, defined as ≤10% residual viable tumor cells in the surgical resection specimens. Secondary efficacy objectives include investigator-assessed radiographic response, pathologic complete response, disease-free survival, event-free survival, overall survival and circulating-tumor DNA clearance rate. This trial will also evaluate exploratory biomarkers pre- and post-treatment in tissue and blood and their correlation with clinical outcomes. -
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P03.05 - CANOPY-N: Neoadjuvant Canakinumab and Pembrolizumab in Patients With Surgically Resectable Non-Small Cell Lung Cancer (ID 2981)
00:00 - 00:00 | Presenting Author(s): Jay M. Lee
- Abstract
Introduction
Complete surgical resection is the standard treatment for patients with stage I-IIIA non-small cell lung cancer (NSCLC). 5-year survival rates range from 19-50%, with most patients dying from distant recurrence. Neoadjuvant or adjuvant chemotherapy improves overall survival by only 5% in patients with NSCLC, and new treatment options are needed. Preliminary data with PD-1 or PD-L1 inhibitors as neoadjuvant therapy has shown major pathologic responses (MPR) or pathologic complete responses (pCR) in patients with early stage NSCLC. CANTOS study demonstrated reduced incidence of NSCLC and decreased lung cancer-related mortality with canakinumab (an IL-1β inhibitor) versus placebo, in dose-dependent manner for patients with atherosclerosis. In preclinical NSCLC humanized models, treatment with canakinumab with or without an anti PD-1 inhibitor demonstrated anti-tumor activity. Combination of canakinumab and pembrolizumab is expected to enhance efficacy of PD-1 inhibition by inhibiting dysregulated inflammation in tumor microenvironment. Based on available evidence, CANOPY-N study was designed to evaluate effect of canakinumab and pembrolizumab as monotherapy or in combination as neoadjuvant treatment for patients with resectable NSCLC.
Methods
CANOPY-N (NCT03968419) is a phase II, randomized, open-label study evaluating effect of canakinumab or pembrolizumab monotherapy or in combination as neoadjuvant treatment in resectable NSCLC patients. Patients will be randomized (stratified by histology [squamous/non-squamous]) to receive a total of 2 doses of canakinumab alone or in combination with pembrolizumab or pembrolizumab with safety follow-up up to 130 days from last study drug dose (Figure 1). Patient eligibility criteria is listed in Table 1. Primary endpoint is to determine MPR rate (≤10% of residual viable tumor cells at time of surgery). Secondary endpoints include determination of overall response rate, MPR rate based on local review, surgical feasibility rates, anti-drug antibodies incidence and pharmacokinetic parameters. Surgery-related safety is one of the exploratory endpoints.
Table 1: Eligibility Criteria
Key Inclusion Criteria
Key Exclusion Criteria
Age ≥18 years
Histologically confirmed stage IB–IIIA NSCLC
Eastern Cooperative Oncology Group performance status 0 or 1
Eligible for surgery, with a planned surgical resection in ~4–6 weeks from the first dose of study treatment
Availability of archival (if obtained up to 5 months before 1 day of treatment) or new biopsy
Unresectable or metastatic disease, including brain metastases
History of severe hypersensitivity reactions to monoclonal antibodies
Patients who received prior systemic therapy in the past 3 years before screening
Clinically significant, uncontrolled cardiac disease and/or a recent cardiac event
Major surgery within 4 weeks prior to randomization
Figure 1: Study Design
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P15 - Immuno-biology and Novel Immunotherapeutics (Phase I and Translational) - Novel Immunotherapeutics (Phase I) (ID 154)
- Event: WCLC 2020
- Type: Posters
- Track: Immuno-biology and Novel Immunotherapeutics (Phase I and Translational)
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P15.08 - Phase I Trial of in situ Vaccination With Autologous CCL21-Modified Dendritic Cells (CCL21-DC) Combined With Pembrolizumab for Advanced NSCLC (ID 1648)
00:00 - 00:00 | Author(s): Jay M. Lee
- Abstract
Introduction
Effective immunotherapy options are lacking for patients with advanced non-small cell lung cancer (NSCLC) who progress on a programmed cell death-(ligand)1 [PD-(L)1] inhibitor and for those that are epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) rearrangement positive after progression on tyrosine kinase inhibitor (TKI) therapy. One potential approach to improve immune checkpoint efficacy in these patient populations is to promote cytolytic T cell infiltration into tumors. This can be accomplished via in situ vaccination with functional antigen presenting cells (APCs) which can take advantage of the full repertoire of tumor antigens and convert the tumor into a lymph node-like environment promoting both local and systemic T cell activation. The chemokine CCL21 promotes co-localization of naive T cells and antigen-experienced dendritic cells (DCs) to facilitate T cell activation. Our preclinical studies and phase I trial of intratumoral (IT) administration of DC genetically modified to overexpress CCL21 (CCL21-DC) revealed augmentation of tumor antigen presentation in situ, resulting in effective T cell responses and systemic antitumor immunity. However, increased PD-L1 expression was observed in a subset of patient tumors, suggesting that tumor-mediated impairment of T cell function may be forestalling a more robust CCL21-DC mediated antitumor response. Similarly, improved PD-(L)1 inhibitor efficacy may be possible with enhanced T cell infiltration and augmented APC function following IT CCL21-DC. Therefore, we are conducting a phase I trial, combining IT CCL21-DC with pembrolizumab in patients with advanced NSCLC that are either (1) EGFR/ALK wild-type after progression on a PD-(L)1 inhibitor or (2) EGFR/ALK mutant after progression on TKI therapy.
Methods
This is a phase I, single institution, non-randomized, dose-escalating, multi-cohort trial followed by dose expansion. A maximum of 24 patients (9-12 escalation + 12 expansion) with stage IV NSCLC will be evaluated who have tumors accessible for IT injection and are either (1) EGFR/ALK wild-type after progression on a PD-(L)1 inhibitor or (2) EGFR/ALK mutant after progression on TKI therapy. Three IT injections of autologous CCL21-DC (days 0, 21, 42) will be concurrently administered with pembrolizumab, followed by q3wk pembrolizumab up to 1 year. Primary objective of dose escalation is safety and determination of maximum tolerated dose (MTD) of IT CCL21-DC (5x106, 1x107, or 3x107) when combined with pembrolizumab. Primary objective of dose expansion is objective response rate (ORR) of CCL21-DC at MTD combined with pembrolizumab. Secondary objectives include adverse event profiling and determination of drug target activity by immune monitoring studies. This trial, NCT03546361, is currently open for enrollment.
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PS01 - Presidential Symposium (Japanese, Mandarin, Spanish Translation Available) (ID 143)
- Event: WCLC 2020
- Type: Plenary
- Track: N.A.
- Presentations: 1
- Moderators:
- Coordinates: 1/30/2021, 07:00 - 09:00, Scientific Program Auditorium
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PS01.05 - Surgical and Clinical Outcomes With Neoadjuvant Atezolizumab in Resectable Stage IB–IIIB NSCLC: LCMC3 Trial Primary Analysis (ID 3195)
07:00 - 09:00 | Presenting Author(s): Jay M. Lee
- Abstract
- Presentation
Introduction
Here we report surgical and clinical outcomes in the Phase II LCMC3 (NCT02927301) study evaluating pre-operative treatment with atezolizumab (anti-PD-L1) in untreated stage IB-IIIB resectable NSCLC.
Methods
Patients with stage IB-IIIB resectable NSCLC and ECOG PS 0/1 were eligible. Patients received neoadjuvant atezolizumab 1200 mg intravenously q3w for ≤2 cycles (days 1 and 22) followed by resection (day 40±10). Patients deemed to have benefit continued on adjuvant atezolizumab for ≤12 months. The primary endpoint was major pathological response (MPR; ≤10% viable tumor cells at surgery) in patients without EGFR/ALK+ mutations. Pre- and post-treatment positron emission tomography/computed tomography scans, pulmonary function tests and biospecimens were obtained. For safety analyses, adverse events (AEs) were classified as treatment-related (TRAE) or immune-related (irAE) and as pre-operative or post-operative (AE onset on or after date of surgery).
Results
Follow-up data from post-surgery visit were analyzed for all enrolled and dosed patients with NSCLC (N=181). Baseline characteristics were: mean age, 65.1 years; female, 93/181 (51%); current smoker, 35/181 (19%); nonsquamous histology, 112/181 (62%); and clinical stages IB (n=16), IIA (n=20), IIB (n=60), IIIA (n=71) and IIIB (n=14). In patients without EGFR/ALK mutations who underwent surgery, the MPR rate was 20% (30/147; 95% CI: 14%-28%) and the pathological complete response rate was 7% (10/147; 95% CI: 3%-12%) (see Carbone, WCLC 2020). Surgical and clinical outcomes and perioperative AEs are in the Table. Following atezolizumab, unresectability was detected pre-operatively in 22/181 (12%) and intra-operatively in 7/159 (4%). The majority of patients (151/159; 95%) had anatomic resections; only 15/101 (15%) converted to thoracotomy. Pathologic downstaging was seen in 57/181 (31%). Only 19/159 (12%) had surgery outside of protocol window. Intraoperative complications were rare (5/159; 3%). 145/159 (91%) had complete (R0) resection. Postoperative TRAEs and irAEs correlated with fewer viable tumor cells in the resected specimen (both P<0.05; Table). 30- and 30-to-90-day mortality were each 1/159 (0.6%). DFS and OS at 1 year and 18 months will be presented.
Conclusion
Neoadjuvant atezolizumab in resectable stage IB-IIIB NSCLC was well tolerated, with no safety concerns. The 20% MPR rate successfully met the primary study objective and was comparable to that with neoadjuvant cisplatin-based therapy. Following neoadjuvant atezolizumab, resection was performed (1) safely with low perioperative morbidity and mortality, (2) infrequently outside of the protocol window and (3) with high complete resection rates.
Enrolled and Dosed Patients With NSCLC
(N = 181)Clinical vs pathological staging
Pre-treatment
cStagePost-treatment pStage
ypT0N0M0
0
8 (4)
IA1
0
6 (3)
IA2
0
7 (4)
IA3
0
8 (4)
IB
16 (9)
15 (8)
IIA
20 (11)
11 (6)
IIB
60 (33)
42 (23)
IIIA
71 (39)
48 (27)
IIIB
14 (8)
8 (4)
IVA
0
2 (1)
Missing
–
4 (2)
No surgery
–
22 (12)
Patients downstaged following atezolizumab, n (%)
57 (31)
Timing of treatment and surgery
Median time from screening to first dose (range), days
15 (0-82)
Median time from enrolment to first dose (range), days
12 (1-82)
Median time from last cycle to surgical resection (range), days (n = 159)
21 (10-73)
Surgery
Stage
Pre-operative unresectable
Underwent surgery
Intra-operative unresectable
All, n (%)
22 (12)
159 (88)
7 (4)
IA, n
1
19
0
IB, n
1
15
0
IIB, n
8
52
1
IIIA, n
10
61
3
IIIB, n
2
12
3
Patients with disease progression per RECIST while on therapy and had surgery, n (%)
4 (2)
Patients with disease progression per RECIST while on therapy and did not have surgery, n (%)
9 (5)
Patients with surgery outside 10-day window, n (%)
19 (12)
Stage IA, n
2
Stage IB, n
1
Stage IIB, n
9
Stage IIIA, n
5
Stage IIIB, n
2
Median time outside window (range), days
8 (1-45)
Extent of resection
(n = 159)n (%)
Pneumonectomy
14 (9)
Bilobectomy
10 (6)
Lobectomy
125 (79)
Segmentectomy
2 (1)
Wedge
3 (2)
Other
5 (3)
Mortality
Deaths before planned surgery, n (%)a
0
Deaths ≤ 30 days after surgery, n (%)
1b (0.6)
Deaths between > 30 and ≤ 90 days after surgery, n (%)
1c (0.6)
Hospitalization
Median length of hospitalization (range), days (n = 48)
7.5 (2-68)
Intra-operative events (post hoc descriptive analysis)
Bronchial complications, n (%)
1 (1)
Vascular complications, n (%)
4 (3)
Lymphadenopathy, n (%)
46 (29)
Peripheral adhesions, n (%)
43 (27)
Peri-hilar/lobar adhesions, n (%)
42 (26)
Pathology
Completeness of resection, n (%)
R0
145 (91)
R1
7 (4)
R2
7 (4)
TRAE
Pre-operative
(n = 181)Post-operative
(n = 159)Any TRAE, n (%)
101 (56)
57 (36)
Grade 3-4
9 (5)
20 (13)
Grade 5
0
1 (1)
irAE
Pre-operative
(n = 181)Post-operative
(n = 159)Any irAE, n (%)
44 (24.3)
43 (27.0)
Grade 3-4
4 (2.2)
12 (8)
Grade 5
0
1 (0.6)
cStage, clinical stage; pStage, pathological stage; VAT, video-assisted thoracic surgery.
a Planned to occur on Day 40 ± 10 of the study. b Due to sudden death, not otherwise specified.
c Due to pneumonitis, deemed related to atezolizumab.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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PS02 - Presidential Symposium (Re-Broadcast) (Japanese, Mandarin, Spanish Translation Available) (ID 275)
- Event: WCLC 2020
- Type: Plenary
- Track: N.A.
- Presentations: 1
- Moderators:
- Coordinates: 1/30/2021, 18:00 - 20:00, Scientific Program Auditorium
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PS02.05 - Surgical and Clinical Outcomes With Neoadjuvant Atezolizumab in Resectable Stage IB–IIIB NSCLC: LCMC3 Trial Primary Analysis (ID 4286)
18:00 - 20:00 | Presenting Author(s): Jay M. Lee
- Abstract
Introduction
Here we report surgical and clinical outcomes in the Phase II LCMC3 (NCT02927301) study evaluating pre-operative treatment with atezolizumab (anti-PD-L1) in untreated stage IB-IIIB resectable NSCLC. Methods
Patients with stage IB-IIIB resectable NSCLC and ECOG PS 0/1 were eligible. Patients received neoadjuvant atezolizumab 1200 mg intravenously q3w for ≤2 cycles (days 1 and 22) followed by resection (day 40±10). Patients deemed to have benefit continued on adjuvant atezolizumab for ≤12 months. The primary endpoint was major pathological response (MPR; ≤10% viable tumor cells at surgery) in patients without EGFR/ALK+ mutations. Pre- and post-treatment positron emission tomography/computed tomography scans, pulmonary function tests and biospecimens were obtained. For safety analyses, adverse events (AEs) were classified as treatment-related (TRAE) or immune-related (irAE) and as pre-operative or post-operative (AE onset on or after date of surgery). Results
Follow-up data from post-surgery visit were analyzed for all enrolled and dosed patients with NSCLC (N=181). Baseline characteristics were: mean age, 65.1 years; female, 93/181 (51%); current smoker, 35/181 (19%); nonsquamous histology, 112/181 (62%); and clinical stages IB (n=16), IIA (n=20), IIB (n=60), IIIA (n=71) and IIIB (n=14). In patients without EGFR/ALK mutations who underwent surgery, the MPR rate was 20% (30/147; 95% CI: 14%-28%) and the pathological complete response rate was 7% (10/147; 95% CI: 3%-12%) (see Carbone, WCLC 2020). Surgical and clinical outcomes and perioperative AEs are in the Table. Following atezolizumab, unresectability was detected pre-operatively in 22/181 (12%) and intra-operatively in 7/159 (4%). The majority of patients (151/159; 95%) had anatomic resections; only 15/101 (15%) converted to thoracotomy. Pathologic downstaging was seen in 57/181 (31%). Only 19/159 (12%) had surgery outside of protocol window. Intraoperative complications were rare (5/159; 3%). 145/159 (91%) had complete (R0) resection. Postoperative TRAEs and irAEs correlated with fewer viable tumor cells in the resected specimen (both P<0.05; Table). 30- and 30-to-90-day mortality were each 1/159 (0.6%). DFS and OS at 1 year and 18 months will be presented. Conclusion
Neoadjuvant atezolizumab in resectable stage IB-IIIB NSCLC was well tolerated, with no safety concerns. The 20% MPR rate successfully met the primary study objective and was comparable to that with neoadjuvant cisplatin-based therapy. Following neoadjuvant atezolizumab, resection was performed (1) safely with low perioperative morbidity and mortality, (2) infrequently outside of the protocol window and (3) with high complete resection rates.
Enrolled and Dosed Patients With NSCLC
(N = 181)Clinical vs pathological staging
Pre-treatment
cStagePost-treatment pStage
ypT0N0M0
0
8 (4)
IA1
0
6 (3)
IA2
0
7 (4)
IA3
0
8 (4)
IB
16 (9)
15 (8)
IIA
20 (11)
11 (6)
IIB
60 (33)
42 (23)
IIIA
71 (39)
48 (27)
IIIB
14 (8)
8 (4)
IVA
0
2 (1)
Missing
–
4 (2)
No surgery
–
22 (12)
Patients downstaged following atezolizumab, n (%)
57 (31)
Timing of treatment and surgery
Median time from screening to first dose (range), days
15 (0-82)
Median time from enrolment to first dose (range), days
12 (1-82)
Median time from last cycle to surgical resection (range), days (n = 159)
21 (10-73)
Surgery
Stage
Pre-operative unresectable
Underwent surgery
Intra-operative unresectable
All, n (%)
22 (12)
159 (88)
7 (4)
IA, n
1
19
0
IB, n
1
15
0
IIB, n
8
52
1
IIIA, n
10
61
3
IIIB, n
2
12
3
Patients with disease progression per RECIST while on therapy and had surgery, n (%)
4 (2)
Patients with disease progression per RECIST while on therapy and did not have surgery, n (%)
9 (5)
Patients with surgery outside 10-day window, n (%)
19 (12)
Stage IA, n
2
Stage IB, n
1
Stage IIB, n
9
Stage IIIA, n
5
Stage IIIB, n
2
Median time outside window (range), days
8 (1-45)
Extent of resection
(n = 159)n (%)
Pneumonectomy
14 (9)
Bilobectomy
10 (6)
Lobectomy
125 (79)
Segmentectomy
2 (1)
Wedge
3 (2)
Other
5 (3)
Mortality
Deaths before planned surgery, n (%)a
0
Deaths ≤ 30 days after surgery, n (%)
1b (0.6)
Deaths between > 30 and ≤ 90 days after surgery, n (%)
1c (0.6)
Hospitalization
Median length of hospitalization (range), days (n = 48)
7.5 (2-68)
Intra-operative events (post hoc descriptive analysis)
Bronchial complications, n (%)
1 (1)
Vascular complications, n (%)
4 (3)
Lymphadenopathy, n (%)
46 (29)
Peripheral adhesions, n (%)
43 (27)
Peri-hilar/lobar adhesions, n (%)
42 (26)
Pathology
Completeness of resection, n (%)
R0
145 (91)
R1
7 (4)
R2
7 (4)
TRAE
Pre-operative
(n = 181)Post-operative
(n = 159)Any TRAE, n (%)
101 (56)
57 (36)
Grade 3-4
9 (5)
20 (13)
Grade 5
0
1 (1)
irAE
Pre-operative
(n = 181)Post-operative
(n = 159)Any irAE, n (%)
44 (24.3)
43 (27.0)
Grade 3-4
4 (2.2)
12 (8)
Grade 5
0
1 (0.6)
cStage, clinical stage; pStage, pathological stage; VAT, video-assisted thoracic surgery.
a Planned to occur on Day 40 ± 10 of the study. b Due to sudden death, not otherwise specified.
c Due to pneumonitis, deemed related to atezolizumab.
