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Daniel B Costa
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MA15 - Colliding Approaches - EGFR and Immunotherapy (ID 916)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 13:30 - 15:00, Room 107
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MA15.02 - Long-Term Safety and Clinical Activity Results from a Phase Ib Study of Erlotinib Plus Atezolizumab in Advanced NSCLC (ID 12095)
13:35 - 13:40 | Author(s): Daniel B Costa
- Abstract
- Presentation
Background
Patients with EGFR mutation–positive non-small cell lung cancer (NSCLC) achieve favorable outcomes with EGFR tyrosine kinase inhibitors (TKIs); however, the long-term efficacy of these agents is limited by development of acquired resistance. Atezolizumab (anti–PD-L1 mAb) monotherapy has shown tolerability and durable clinical activity in NSCLC. By selectively targeting PD-L1 to block its interaction with receptors PD-1 and B7.1, atezolizumab can reinvigorate anti-cancer T-cell activity. Thus, combining atezolizumab and erlotinib could result in improved anti-tumor immunity and durable anti-tumor effects. Safety and preliminary clinical activity from a Phase Ib study of erlotinib plus atezolizumab in locally advanced or metastatic NSCLC have been previously reported (Rudin, et al. WCLC 2016). Here we describe updated findings from this study (NCT02013219).
a9ded1e5ce5d75814730bb4caaf49419 Method
EGFR TKI-naive patients with NSCLC were enrolled into a safety-evaluation stage (Stage 1) regardless of EGFR status, and an expansion stage (Stage 2) enrolled patients with EGFR-mutant NSCLC who were previously untreated or treated with 1 prior non–EGFR TKI therapy. A 7-day run-in period with erlotinib 150 mg PO QD was followed by addition of atezolizumab 1200 mg IV q3w. The primary endpoint was safety/tolerability of the combination; secondary endpoints included clinical activity per RECIST v1.1.
4c3880bb027f159e801041b1021e88e8 Result
At data cutoff (August 18, 2017), 28 patients (Stage 1, n = 8; Stage 2, n = 20) were evaluable for safety, and the median survival follow-up was 26.0 months (range, 7.8-32.9; Stage 2). The median age was 61 years (range, 47-84), and the most common EGFR mutation was exon 19 deletion (44%). Grade 3 treatment-related AEs (TRAEs) were reported in 43% of patients; no Grade 4 or 5 TRAEs occurred. The most common TRAEs were increased ALT, pyrexia, rash and diarrhea (2 patients each). Serious AEs occurred in 54% of patients; treatment-emergent AEs led to atezolizumab discontinuation in 18% and erlotinib discontinuation in 11%. Clinical activity was evaluated in Stage 2 patients. ORR was 75% (95% CI: 50.9, 91.3), with a median DOR of 16.7 months (range, 4.2-26.0+). Median PFS was 15.4 months (95% CI: 8.4, not estimable [NE]), and median OS was 32.7 months (95% CI: 32.7, NE).
8eea62084ca7e541d918e823422bd82e Conclusion
Atezolizumab plus erlotinib demonstrated a tolerable safety profile and compared favorably with prior reports of efficacy with erlotinib monotherapy. OS data are expected to mature and improve with longer follow-up; updated clinical and biomarker data will be presented. Further investigation of the combination is warranted to assess its full potential.
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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OA02 - Novel Therapies in ROS1, HER2 and EGFR (ID 893)
- Event: WCLC 2018
- Type: Oral Abstract Session
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 10:30 - 12:00, Room 105
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OA02.08 - Discussant - OA 02.05, OA 02.06, OA 02.07 (ID 14549)
11:45 - 12:00 | Presenting Author(s): Daniel B Costa
- 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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P1.13 - 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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P1.13-44 - Safety, PK, and Preliminary Antitumor Activity of the Oral EGFR/HER2 Exon 20 Inhibitor TAK-788 in NSCLC (ID 12373)
16:45 - 18:00 | Author(s): Daniel B Costa
- Abstract
Background
TAK-788 (AP32788) is an investigational tyrosine kinase inhibitor (TKI) with potent, selective preclinical activity against activating EGFR and HER2 mutations, including exon 20 insertions. We report early results of a phase 1/2 first-in-human, open-label, multicenter study of TAK-788 (NCT02716116).
a9ded1e5ce5d75814730bb4caaf49419 Method
Patients with advanced non-small cell lung cancer (NSCLC) refractory to standard therapy received daily oral doses (5–120 mg) of TAK-788 in the ongoing dose-escalation phase (3+3 design). Preliminary antitumor activity (by RECIST v1.1), safety, and PK are reported for patients who received ≥1 dose.
4c3880bb027f159e801041b1021e88e8 Result
As of 8-Sep-2017, 34 patients (median age, 60 y; female, 65%; ≥2 prior anticancer therapies, 88%; Table) were treated with TAK-788; 10 remain on treatment at data cutoff. AUC0‑24,ss increased in a dose-proportional manner over the dose range evaluated; the effective t1/2 was ~16 (range 6–28) h. The most common treatment-emergent AEs (TEAEs; ≥20%) were diarrhea (47%), nausea (26%), and fatigue (21%). Grade ≥3 TEAEs in ≥2 patients (excluding disease progression) were dyspnea (n=3, 9%) and anemia, asthenia, dehydration, lung infection, pleural effusion, pneumonia, and pneumonitis (n=2 each, 6%). Two DLTs, both pneumonitis, were reported (80 mg, grade 3; 120 mg, grade 5). Of 14 evaluable patients, 3 had PR (80 mg, n=2, both confirmed; 120 mg, single PR awaiting confirmation), 6 had SD (40 mg, n=3; 80 mg, n=2; 120 mg, n=1), and 5 had PD as best response (40 mg, n=3; 80 mg, n=1; 120 mg, n=1). All patients with PR had EGFR exon 20 insertions.
8eea62084ca7e541d918e823422bd82e Conclusion
TAK-788 exhibits antitumor activity in patients with EGFR exon 20 insertions with an AE profile consistent with other EGFR TKIs. Phase 2 will begin after determination of the RP2D, with 4 molecularly defined cohorts in NSCLC. Updated data will be presented, including the recommended phase 2 dose (RP2D).
Baseline Characteristics 5 mg
(n=4)10 mg
(n=5)20 mg
(n=5)40 mg
(n=6)80 mg
(n=7)120 mg
(n=7)Total
(n=34)Mutation type,a %
Common EGFR mutations (exon 19 deletion / L8585R) 25 20 0 0 0 0 6 EGFR-T790M+ 0 0 0 0 14 0 3 EGFR exon 20 insertion 50 40 60 83 71 57 62 HER2 0 20 40 17 14 29 21 a One patient (20 mg) had both EGFR and HER2 mutations; 1 patient (80 mg) had EGFR exon 20 insertion + T790M.
6f8b794f3246b0c1e1780bb4d4d5dc53
