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Edward B Garon
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MA04 - Novel Approaches with IO (ID 900)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Immunooncology
- Presentations: 2
- Moderators:
- Coordinates: 9/24/2018, 13:30 - 15:00, Room 107
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MA04.02 - Responses and Durability in NSCLC Treated With Pegilodecakin and Anti-PD-1 (ID 13986)
13:35 - 13:40 | Presenting Author(s): Edward B Garon
- Abstract
- Presentation
Background
Responses in NSCLC to agents targeting the PD-1/PD-L1 axis are correlated with PD-L1 expression by immunohistochemistry (IHC), tumor mutational burden (TMB), interferon-associated mRNA expression profile (GEP), and the absence of liver metastases. Anti-PD-1 impedes the inhibition of T cells while pegilodecakin (AM0010) stimulates the survival and expansion of intratumoral, antigen-activated CD8+ T cells (Mumm et al, 2010). This provides a rationale for combining anti-PD-1 agents with pegilodecakin.
a9ded1e5ce5d75814730bb4caaf49419 Method
Pretreated NSCLC subjects (N = 34) received pegilodecakin (10-20 µg/kg QD, SC) with pembrolizumab (2 mg/kg, Q3W, IV; n = 5) or nivolumab (3 mg/kg, Q2W, IV; n = 29). Median follow-up is 31.2 months (range, 28.3-33+ months) and 17.5 months (range, 8.3- 25.9+ months), respectively. Responses were assessed by irRC. Twenty subjects had sufficient tissue for PD-L1 testing with the 22C3 IHC assay (CLIA) and 10 subjects had sufficient tissue for TMB evaluation by whole exome sequencing (WES) and pretreatment GEP by NanoString.
4c3880bb027f159e801041b1021e88e8 Result
In 26 subjects evaluable for response, the ORR was 41% (11 PRs). Another 12 subjects (46%) had SD as best response. As investigators were asked to preferentially enroll PD-L1–negative patients, PD-L1 expression was <1% in 12 of 20 PD-L1–evaluable subjects with 4 achieving a PR. Ten subjects had sufficient tissue for TMB and GEP, including 6 PRs. Five of the 8 who tested low to intermediate for TMB (<243 mut) had a PR as did 2 of 6 GEP-negative subjects. In addition, 5 of 8 subjects with liver metastasis had a PR. The mPFS and mOS of the 5 NSCLC subjects (4/4 tested PD-L1 <1%) treated with pegilodecakin + pembrolizumab was 10.9 and 32.2 months, respectively. The mPFS and mOS for the pegilodecakin + nivolumab cohort (8/16 tested PD-L1 <1%) has not been reached.
8eea62084ca7e541d918e823422bd82e Conclusion
Pegilodecakin, when added to anti-PD-1 therapy in advanced NSCLC patients, was associated with response rates and durability of benefit greater than has been seen with anti-PD-1 alone. Responses were seen in settings in which anti-PD-1 therapy has demonstrated limited benefit, such as absent PD-L1 expression, low TMB, and/or the presence of liver metastasis. These preliminary findings support further studies of pegilodecakin with anti-PD-1 therapies.
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MA04.09 - Neoadjuvant Atezolizumab in Resectable Non-Small Cell Lung Cancer (NSCLC): Updated Results from a Multicenter Study (LCMC3) (ID 12941)
14:30 - 14:35 | Author(s): Edward B Garon
- Abstract
- Presentation
Background
Cisplatin-based chemotherapy, before or after surgery, provides only a 5% benefit in 5yr. OS in resectable NSCLC. A 20 patient study (NEJM April 2018) showed that preoperative immune checkpoint inhibitor therapy yielded a clinically meaningful major pathologic response rate (MPR ≤10% residual viable tumor cells) and did not delay or complicate surgery. This large multicenter trial measures MPR and biomarkers of benefit using neoadjuvant atezolizumab (atezo) [NCT02927301].
a9ded1e5ce5d75814730bb4caaf49419 Method
We planned 2 cycles of atezo (1200mg, days 1, 22) in patients with stages IB -selected IIIB resectable NSCLC prior to surgical resection (day 40 +/- 10). Chest CT, PET were planned pre-atezo and presurgery to assess response. Primary tumor +/- node biopsies and blood samples were obtained before atezo and presurgery for biomarker studies. The primary endpoint was MPR. Secondary endpoints included safety, response by PD-L1, OS, and DFS.
4c3880bb027f159e801041b1021e88e8 Result
For this updated efficacy and safety analysis (Feb’18 datacut), we report first 54 of 180 planned pts: 29 males, median age 65 yr, all ECOG 0-1; 17 current, 33 former smokers; 35 non-squamous NSCLC; clinical stages Ib/IIa/IIb/IIIa/IIIb = 5/11/13/20/5. Two pts received one dose of atezo due to treatment related AE (Gr 1 pyrexia, Gr 2 dyspnea) but underwent uncomplicated resection with MPR assessment. There was 1 unrelated Gr 5 AE (sudden cardiac death post surgical resection), 16 Gr 3-4 AEs (3 treatment related). Surgery was delayed in 1 pt due to Gr3 pneumonitis. By RECIST, 3 pts had PR, and 49 had SD. 50 pts underwent surgery and 47 pts had MPR assessment: 2 pts discontinued study preop due to radiographic PD and 2 discontinued due to other reasons; 3 pts had unresectable disease. MPR rate was 10/50 (20%, 95% CI 10-34%) including 3 pts who had pCR (no viable tumor cells) in the primary tumor. Excluding 5 pts who had known driver mutations (4 EGFR+, 1 ALK+), MPR rate was 10/45 (22%, 95% CI 11-37%). PD-L1 status was evaluable in 44/54 pts; 8/10 pts with MPR had PD-L1+ status and 2 had unknown PD-L1 status; 8/28 PDL-1 (+) patients had MPR (29%).
8eea62084ca7e541d918e823422bd82e Conclusion
In a multicenter study, neoadjuvant atezo was well tolerated. MPR rate is encouraging. Clinical and pathological responses are often discordant. Correlative analyses on pre- and post atezo tissues are ongoing. Preliminary correlative analyses in blood samples are included in a separate abstract.
6f8b794f3246b0c1e1780bb4d4d5dc53Only 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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MS28 - IO Combinations in Advanced NSCLC (ID 806)
- Event: WCLC 2018
- Type: Mini Symposium
- Track: Immunooncology
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 13:30 - 15:00, Room 106
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MS28.01 - Understanding the Rationale for Combining IO Agents (ID 11520)
13:30 - 13:45 | Presenting Author(s): Edward B Garon
- Abstract
- Presentation
Abstract not provided
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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P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.01-104 - Updated Phase I Results of Carboplatin, Pemetrexed and Exemestane in Postmenopausal Women with Metastatic Non-Squamous NSCLC (ID 14158)
16:45 - 18:00 | Author(s): Edward B Garon
- Abstract
Background
Estrogen receptors (ERa, ERb) and aromatase (key enzyme for estrogen synthesis) are expressed in most human NSCLCs. High intratumoral estrogens and elevated aromatase expression in NSCLC predicts poor outcome. In vitro preclinical models show that estrogen stimulates NSCLC gene expression, induces proliferation, and diminishes apoptosis. Furthermore, preclinical NSCLC models demonstrate that antiestrogens or aromatase inhibitors prevent these processes and that the combination of cisplatin and aromatase inhibitors elicits dramatic growth inhibition (Marquez et al., Annals NY Acad Sci. 2009;1155:194). Additionally, depletion of autocrine/paracrine estrogen production hypersensitizes cells to DNA-damaging effects of platinum therapy, thereby providing support for this early phase trial.
a9ded1e5ce5d75814730bb4caaf49419 Method
The primary objective of this phase 1b, open-label, single-center study (NCT01664754) was to evaluate safety and tolerability of escalating doses of exemestane in combination with carboplatin and pemetrexed in postmenopausal women with stage IV non-squamous NSCLC. Key exclusion criteria included untreated CNS involvement, major surgery in prior 4-weeks to therapy, prior/concurrent investigational or standard therapy (with exception of TKI and/or immunotherapy in prior 4-weeks). Patients received escalating doses of exemestane (starting 1-week before chemotherapy) at 25 mg PO daily (Cohort 1) or 50 mg PO daily (Cohort 2) combined with carboplatin (AUC 6 mg x min/mL) and pemetrexed (500 mg/m2) IV q3 weeks for 4 cycles. After 4 cycles, patients were eligible for continued therapy with exemestane and/or pemetrexed. Area under the curve (AUC) was extrapolated using linear trapezoidal methods.
4c3880bb027f159e801041b1021e88e8 Result
Ten patients consented for therapy; 2 patients screen-failed. Three patients completed therapy in Cohort 1, and five patients were treated in Cohort 2. One patient in Cohort 2 exited the trial for alternative therapy after one treatment cycle. The median number of cycles given was 15 (range 1-54). The mean of the maximum serum concentration (Cmax) of exemestane for Cohort 1 was 12.98 ng/mL and for Cohort 2 was 41.38 ng/mL. The AUCinffor the two cohorts was 51.73 and 184.17 ng x h/mL, respectively. The established maximum tolerated dose (MTD) was exemestane 50 mg PO daily with pemetrexed (500 mg/m2 IV q3 weeks) and carboplatin (AUC 6 mg x min/mL IV q3 weeks). No patients were removed from the study for adverse events. Clinical outcome, biomarker and QOL correlates are being collected.
8eea62084ca7e541d918e823422bd82e Conclusion
The combination of carboplatin, pemetrexed and exemestane in post-menopausal women with metastatic non-squamous, NSCLC is safe and well-tolerated. This data supports future clinical trials to establish efficacy with this combination therapy.
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P1.04 - Immunooncology (Not CME Accredited Session) (ID 936)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.04-14 - HLA B44 Supertype Associated with Less Favorable Neoantigen Binding in Non-Small Cell Lung Cancer Treated with Immunotherapy (ID 12285)
16:45 - 18:00 | Author(s): Edward B Garon
- Abstract
Background
Human leukocyte antigen (HLA) supertypes may influence immunotherapy efficacy, particularly HLA class 1 B44 supertype (B44), which is found in 35-55% of the population irrespective of race (Sidney, BMC Immunol). In melanoma patients treated with immune checkpoint inhibitors, presence of B44 correlated with improved survival (Chowell, Science), but in a cohort of 58 non-small cell lung cancer (NSCLC) patients treated with single-agent pembrolizumab, B44 was associated with poorer outcomes (Lu, ASCO 2018). Given B44’s small electropositive binding pocket, it was hypothesized that the transversions that predominate in NSCLC result in more positive tumor variant amino acids (vAAs) and that these neoantigens would have decreased binding affinity and/or HLA B44:peptide stability.
a9ded1e5ce5d75814730bb4caaf49419 Method
58 advanced NSCLC patients treated with pembrolizumab had germline and tumor multiplexed paired-end Illumina WES performed. HLA typing used BWA-ALN and Athlates software; supertype was determined by 2008 criteria (Sidney, BMC Immunol). Six subjects with at least one strong HLA B44 supertype allele had nonsynonymous coding mutations identified with Genome Toolkit Analysis (GATK) best practices utilizing the Hg38 genome reference. PvacSeq software used NetMHC algorithms to identify tumor neoantigens 9 base pairs in length matched to their corresponding HLA B44 allele (B44-specific neoantigens, BSNs). Missense BSNs were classified by transition (Ti) transversion (Tv) ratios and vAA charge change. TiTv was compared with matched pairs analysis. Predicted NetMHC IC50 binding affinities were compared with student’s t-tests. All statistical analyses were performed with SAS JMP, Version 13.0 (Cary, NC).
4c3880bb027f159e801041b1021e88e8 Result
Among the 6 subjects, 3073 BSNs were identified; 1090 were unique. There were no common BSNs among subjects. Subject tumor TiTv median was 1.58 (95% CI 1.09-1.94), mean difference compared to germline was -0.62 (95% CI -1.11 to -0.12, p=0.02). BSNs with vAAs that changed charge represented 13.5% of all BSNs. Positive vAA charge changes were as expected based on theoretical distribution (12.5% Tv vs 6.3% Ti, p=0.02). In aggregate, there were 205 BSNs with negative charge change (-BSN) and 204 with positive charge change (+BSN). The anticipated HLA B44 binding affinity was lower for +BSN, with median NetMHC IC50 binding 176.2 (95% CI 178.0-217.9) vs 258.6 (95% CI 216.9-257.7) for -BSN, p<0.01.
8eea62084ca7e541d918e823422bd82e Conclusion
A potential mechanism for decreased survival in B44 NSCLC subjects treated with immunotherapy is unfavorable neoantigen binding related to increased transversions leading to tumor vAAs with positive charge changes and poorer HLA B44 binding. All subjects from this cohort will be evaluated for BSNs 8-12 base-pairs long to confirm these findings.
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P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.13-30 - Neutrophil-to-Lymphocyte Ratio as a Prognostic Factor and its Relationship to NSCLC Patient Outcomes in the REVEL Trial (ID 13126)
16:45 - 18:00 | Author(s): Edward B Garon
- Abstract
Background
Neutrophil-to-lymphocyte ratio (NLR) reflects underlying levels of systemic inflammation and has prognostic importance in solid tumors. Higher baseline NLR is an independent negative prognostic factor in advanced non–small cell lung cancer (NSCLC) and may indicate more aggressive disease. An exploratory analysis from REVEL demonstrated benefits of ramucirumab(RAM)/docetaxel(DOC) in NSCLC patients with rapidly progressing and refractory disease. We investigated the relationship between pretreatment NLR, prognosis and response to RAM/DOC.
a9ded1e5ce5d75814730bb4caaf49419 Method
Pretreatment NLR was analyzed by dividing absolute neutrophil count by absolute lymphocyte count from peripheral blood. Multiple NLR cutoffs ≥4 were evaluated for prognostic significance by analyzing overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Kaplan-Meier analysis and Cox proportional hazards regression model were used for analyzing OS and PFS, and Cochran-Mantel-Haenszel test for ORR.
4c3880bb027f159e801041b1021e88e8 Result
Pretreatment NLR was determined for 1224 REVEL patients (n=611 RAM/DOC, n=613 placebo [PBO]/DOC), among whom 51%, 40%, and 32% had NLR ≥4, 5, and 6, respectively. Baseline characteristics were balanced between arms in NLR subgroups and the REVEL intent-to-treat (ITT) population. Patients with higher NLR values had worse OS, PFS, and ORR compared to the ITT population. For all NLR cutoff values, OS, PFS and ORR were improved in patients treated with RAM/DOC compared to patients receiving PBO/DOC (Table). Efficacy and safety outcomes across high NLR subgroups were consistent with those in the ITT population.
8eea62084ca7e541d918e823422bd82e Conclusion
In this exploratory analysis of REVEL, higher pretreatment NLR was an independent prognostic factor indicating poorer survival outcomes. Treatment benefit with RAM/DOC was preserved in patients with elevated NLR and was consistent with REVEL ITT results. NLR is an inexpensive and reproducible blood test and may provide a simple way to identify patients with more aggressive disease who can benefit from treatment with RAM/DOC in second-line NSCLC.
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P2.09 - Pathology (Not CME Accredited Session) (ID 958)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.09-05 - Evaluation of PD-L1-Stained Tumor Cells via the 22C3 and SP-142 Antibodies in Cohort of Patients Treated on KEYNOTE-001 (ID 12976)
16:45 - 18:00 | Author(s): Edward B Garon
- Abstract
Background
Four PD-L1 antibodies have been utilized in NSCLC clinical trials, with an analytical comparison demonstrating a high level of concordance between the percentage of PD-L1–stained tumor cells with three of these antibodies (22C3, 22C3, 28-8, and SP263), but not a fourth, SP-142 (Hirsch et al, JTO 2017). This finding led us to evaluate the relationship between the percentage of PD-L1–stained tumor cells with 22C3 and SP-142, as well as the association between the PD-L1 levels identified by each antibody and clinical outcomes in 28 NSCLC patients treated on KEYNOTE-001.
a9ded1e5ce5d75814730bb4caaf49419 Method
We performed a retrospective analysis of 28 NSCLC patients treated with pembrolizumab on the KEYNOTE-001 trial at UCLA (23pts) or MSKCC (5pts) with data cut-off 12/2017. Patients had PD-L1–stained tumor cell levels assessed by both the 22C3 antibody (Dako), via central evaluation as previously described (Garon et al, NEJM 2015) and the SP-142 antibody (Spring Bioscience) at UCLA in accordance with established methods (Zaretsky et al, NEJM 2016). Survival curves for PFS and OS were estimated using the Kaplan-Meier method and formally compared between groups using the log-rank test. The association between PD-L1–stained tumor cell levels identified by the two antibodies was assessed using the Pearson correlation coefficient.
4c3880bb027f159e801041b1021e88e8 Result
In 61% (17/28) of patients, PD-L1 levels were grouped similarly (either <1%, 1-49%, or >50%) by both antibodies. Specifically, compared to 22C3 staining, SP-142 led to the same grouping for 63% (5/8) pts with >50% staining, 85% (11/13) pts with 1-49% staining, and 14% (1/7) pts w <1% staining. Evaluating the relationship between PD-L1 grouping and clinical outcomes via the SP-142 antibody revealed improved PFS and OS in pts with higher PD-L1 expression levels, while the 22C3 antibody predicted for improved PFS in these patients, but not improved OS [SP142 (PFS,OS): (p=0.0039, p=0.0425)][22C3 (PFS,OS): p=0.0121, p=0.1222). The PD-L1 results from the SP-142 and 22C3 antibodies were strongly associated (r =0.58, p=0.001).
8eea62084ca7e541d918e823422bd82e Conclusion
The PD-L1–stained tumor cell levels in the majority of patients evaluated were similarly grouped into one of three categories (<1%, 1-49%, or >50%) by both 22C3 and SP142. This analysis is limited by small patient number, but suggests that the number of PD-L1–stained tumor cells identified by each antibody is similar and a higher PD-L1 level identified by either antibody predicts for improved clinical outcomes with pembrolizumab.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P2.13 - Targeted Therapy (Not CME Accredited Session) (ID 962)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.13-39 - A Phase Ib Trial of the HSP90 Inhibitor AUY922 in Combination with Pemetrexed in Metastatic Non-Squamous, Non-Small Cell Lung Cancer Patients (ID 13953)
16:45 - 18:00 | Author(s): Edward B Garon
- Abstract
Background
AUY922 demonstrates preclinical activity in non-small cell lung cancer (NSCLC) cell lines by potently inhibiting HSP90. As a single-agent, AUY922 showed clinical activity for NSCLC patients in a phase II trial, particularly in those with driver mutations in epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), client proteins of HSP90. We previously demonstrated that AUY922 reliably decreases dihydrofolate reductase (DHFR) mRNA expression. Therefore, we conducted a phase Ib trial of the combination of AUY922 with pemetrexed, an antifolate inhibitor of DHFR.
a9ded1e5ce5d75814730bb4caaf49419 Method
In the dose-escalation portion, 9 patients with previously-treated metastatic non-squamous NSCLC were treated using a standard 3 + 3 design with pemetrexed at the standard 500 mg/m2 dose, plus: AUY922 40 mg/m2, 55 mg/m2, or 70 mg/m2 per week, respectively. After the maximum tolerated dose (MTD) was determined, an additional 4 patients were treated at the MTD. The primary endpoint was safety and tolerability.
4c3880bb027f159e801041b1021e88e8 Result
Of 13 total patients, 9 (70%) harbored an EGFR mutation. Two grade 3 dose-limiting toxicities were observed in the 70 mg/m2 cohort (thrombocytopenia and supraventricular tachycardia). Therefore, the MTD was determined to be 55 mg/m2 with pemetrexed. At the MTD, 71% (n=5) required a dose reduction, with a median relative dose intensity (RDI) of 88%. Common drug-related adverse events (DRAE) included ocular toxicity or visual disturbances (n=9, 70%), fatigue (n=6, 46%), diarrhea (n=5, 38%), anemia (n=5, 38%), anorexia (n=4, 31%), and nausea (n=3, 23%). There were no grade 4-5 events. Maximum serum concentration (Cmax) of AUY922 was associated with increased grade 2 DRAEs (rs = 0.74, p < 0.01). The volume of distribution (VZ) was inversely associated with number of DRAEs (rs = -0.81, p = 0.004) and number of ophthalmologic related DRAEs (rs = -0.65, p = 0.04). The best response was partial response in one patient for 20 months, prior to expiration of all AUY922. Immunohistochemistry of available pre-treatment tumor tissue (n = 10) revealed that this responder was also the only patient with tumor DHFR cytoplasmic and membranous pattern staining (2 to 3+ intensity).
8eea62084ca7e541d918e823422bd82e Conclusion
In patients with previously treated metastatic non-squamous NSCLC, the MTD of AUY922 in combination with pemetrexed was determined to be 55 mg/m2 per week. DHFR expression was seen only in the one long-term responder, but relevance is difficult to determine based on limited patient number based in part to closure of the study for lack of unexpired drug. Tolerability of AUY922 with pemetrexed is limited by ocular toxicity.
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P3.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 982)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.16-02 - Phase III Study of Canakinumab (ACZ885) as Adjuvant Therapy in Patients with Surgically Resected NSCLC (ID 12069)
12:00 - 13:30 | Presenting Author(s): Edward B Garon
- Abstract
Background
Preclinical and clinical data suggest that cytokines such as interleukin (IL)-1β can promote angiogenesis and tumor growth, and are essential to tumor invasiveness. Canakinumab (ACZ885) is a high-affinity human IgGκ anti-IL-1β monoclonal antibody approved for patients with various IL-1–driven auto-inflammatory diseases. In the Phase III Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) in patients with atherosclerosis, canakinumab was associated with a significant reduction in the incidence of fatal and non-fatal lung cancer in patients with increased high-sensitivity C-reactive protein levels. ACZ885T2301 (NCT03447769) is evaluating the efficacy and safety of adjuvant canakinumab versus placebo in patients with surgically resected non-small cell lung cancer (NSCLC).
a9ded1e5ce5d75814730bb4caaf49419 Method
This Phase III, randomized, double-blind, placebo-controlled study is enrolling patients (≥18 years, Eastern Cooperative Oncology Group Performance Status ≤1) with completely resected (R0) American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) v.8 stages II−IIIA and IIIB (T >5 cm and N2) NSCLC, who have completed standard-of-care adjuvant treatments, including cisplatin-based chemotherapy and mediastinal radiation therapy (if applicable). Prior treatment with neoadjuvant chemotherapy or radiotherapy is not permitted. Approximately 1500 patients will be randomized 1:1 to receive canakinumab (200 mg every 3 weeks [Q3W], subcutaneous [s.c.]) or placebo (Q3W, s.c.) on Day 1 of 21-day cycles for 18 cycles or until disease recurrence, unacceptable toxicity, treatment discontinuation at the discretion of the investigator or patient, death, or loss to follow-up. Following baseline screening, imaging assessment will be performed every 12 weeks for the first year (treatment phase) following Cycle 1 Day 1, then every 26 weeks during Years 2 and 3, and annually during Years 4 and 5 (post-treatment surveillance phase). Randomization will be stratified by AJCC/UICC v.8 stage, tumor histology, and region.
The primary objective is to compare disease-free survival (DFS) in the canakinumab versus placebo arms, as determined by local investigator assessment. Secondary objectives include a comparison of the two treatment groups with respect to overall survival (key secondary objective), lung cancer-specific survival, safety, pharmacokinetics and immunogenicity of canakinumab, and patient-reported outcomes. Exploratory objectives include assessment of the relationship between pharmacokinetics, pharmacodynamics, safety, and efficacy, and evaluation of correlation between cytokines/soluble markers and efficacy endpoints. Enrollment is ongoing.
4c3880bb027f159e801041b1021e88e8 Result
Section not applicable
8eea62084ca7e541d918e823422bd82e Conclusion
Section not applicable
6f8b794f3246b0c1e1780bb4d4d5dc53
