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Sarah B Goldberg
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MTE21 - Can I Treat Brain Metastasis with Immunotherapy? (Ticketed Session) (ID 831)
- Event: WCLC 2018
- Type: Meet the Expert Session
- Track: Immunooncology
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 07:00 - 08:00, Room 105
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MTE21.01 - Can I Treat Brain Metastasis with Immunotherapy? (ID 11583)
07:00 - 07:30 | Presenting Author(s): Sarah B Goldberg
- Abstract
- Presentation
Abstract not provided
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OA10 - Right Patient, Right Target & Right Drug - Novel Treatments and Research Partnerships (ID 910)
- Event: WCLC 2018
- Type: Oral Abstract Session
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 10:30 - 12:00, Room 106
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OA10.04 - Afatinib With or Without Cetuximab for EGFR-Mutant Non-Small Cell Lung Cancer: Safety and Efficacy Results from SWOG S1403 (ID 14014)
11:05 - 11:15 | Presenting Author(s): Sarah B Goldberg
- Abstract
- Presentation
Background
Several EGFR tyrosine kinase inhibitors (TKIs) are used for the treatment of EGFR-mutant non-small cell lung cancer (NSCLC), however resistance inevitably develops. The combination of the irreversible ErbB family TKI afatinib and the EGFR monoclonal antibody cetuximab was previously shown to overcome resistance to first-line EGFR TKIs. To attempt to delay resistance, we conducted a randomized trial of afatinib plus cetuximab versus afatinib alone in treatment-naïve patients with advanced EGFR-mutant NSCLC (NCT02438722).
a9ded1e5ce5d75814730bb4caaf49419 Method
Patients with previously-untreated EGFR-mutant NSCLC were randomized to afatinib 40mg PO daily plus cetuximab 500mg/m2 IV every 2 weeks or afatinib 40mg PO daily. The study was designed to accrue a total of 212 patients, comparing progression-free survival (PFS) between the arms at the 1-sided 0.025 level when 134 PFS events had been observed. Secondary objectives included comparison of overall survival (OS), time to treatment discontinuation (TTD), and toxicity. An interim analysis evaluating early stopping for futility occurred when at least 64 PFS events were reported.
4c3880bb027f159e801041b1021e88e8 Result
Between March 26, 2015 and April 23, 2018, 170 eligible patients were accrued: 86 to afatinib/cetuximab and 84 to afatinib. Median age was 66.4 years, 66% were female, 64% had an EGFR exon 19 deletion mutation and 36% had an L858R point mutation. With 109 events observed, there was no improvement in PFS with the combination compared to single-agent (HR 1.17, 95% CI 0.80-1.73, P = 0.42, median 10.6 months vs 13.1 months). OS was also not improved with the addition of cetuximab (HR 1.23, 95% CI 0.62-2.44, P = 0.55, median 26.9 months vs not reached). TTD was similar between the two groups (HR 0.95, 95% CI 0.64-1.39, P = 0.79, median 12.5 months vs 12.2 months). Grade > 3 treatment-related adverse events (AEs) were more common among patients treated with afatinib/cetuximab, and more patients in the combination arm required at least 1 dose reduction of afatinib (57% vs 26%). However, treatment discontinuations due to AEs were similar between the two groups (11.6% vs 10.7%).
8eea62084ca7e541d918e823422bd82e Conclusion
There was no difference in PFS, OS or TTD with the addition of cetuximab to afatinib for treatment-naïve patients with EGFR-mutant NSCLC. The trial was closed to accrual at the interim analysis having met the criteria for futility. Correlative analysis of tumor tissue and blood from patients is ongoing.
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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P3.04 - Immunooncology (Not CME Accredited Session) (ID 970)
- 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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P3.04-23 - Phase 1b/2 Study to Evaluate Novel Combinations With Oleclumab (MEDI9447) in Previously Treated Advanced EGFRm NSCLC (ID 12300)
12:00 - 13:30 | Author(s): Sarah B Goldberg
- Abstract
Background
Patients with mutant EGFR (EGFRm) non–small cell lung cancer (NSCLC) have a limited chance of benefiting from treatment with programmed death-1 inhibitors. EGFR activation leads to overexpression of CD73 and may provide a mechanism of immune evasion. CD73 overexpression has also led to worse outcomes in multiple tumor types, including NSCLC. Recent studies demonstrated that an orthogonal therapeutic approach to cancer, such as combining tyrosine kinase inhibitors (TKIs) with immunotherapy, may result in synergistic clinical activity. Oleclumab is a human monoclonal antibody (mAb) that selectively binds to CD73 and inhibits the enzymatic production of adenosine. Adenosine exerts its immunosuppressive effects on various immune cells via the adenosine 2A receptor (A2AR). AZD4635 is a potent, selective A2AR antagonist that inhibits this signaling pathway. Osimertinib is a potent and selective inhibitor of EGFRm, including the T790M resistance mutation. We hypothesize that novel combinations of targeted and immunotherapeutic agents targeting the adenosine pathway will be well tolerated and lead to increased antitumor activity in subjects with EGFRm NSCLC.
a9ded1e5ce5d75814730bb4caaf49419 Method
This is a multi-arm, open-label, multicenter, phase 1b/2 study (NCT03381274) consisting of 2 parts. In Part 1, the safety and tolerability of oleclumab in combination with either osimertinib (Arm A) or AZD4635 (Arm B) will be evaluated, and a recommended phase 2 dose for each combination will be identified. In Part 2, the safety, tolerability, and preliminary antitumor activity will be evaluated. In both parts, patients will be allocated to treatment arms based upon their EGFRm status and their prior therapy. For Part 2, the primary objective of antitumor activity will be assessed by objective response according to RECIST v1.1. Key secondary objectives include additional evaluation of clinical activity, the pharmacokinetic profiles of oleclumab, osimertinib, and AZD4635, and the evaluation of oleclumab immunogenicity. Additional treatment arms may be added as the study progresses. The study is open for enrollment and recruitment is ongoing, with a planned enrollment of up to approximately 98 patients.
4c3880bb027f159e801041b1021e88e8 Result
Section not applicable
8eea62084ca7e541d918e823422bd82e Conclusion
Section not applicable
6f8b794f3246b0c1e1780bb4d4d5dc53
