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Jonathan W Riess
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JCSE 01 - Joint IASLC/CSCO/CAALC Session: Immunotherapy for Management of Lung Cancer: Ongoing Research from East and West (ID 630)
- Event: WCLC 2017
- Type: Joint Session IASLC/CSCO/CAALC
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:C. Bai, Fred R. Hirsch, Tony SK Mok, Yi-Long Wu
- Coordinates: 10/15/2017, 07:30 - 11:30, F203 (Annex Hall)
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JCSE 01.14 - Discussant Poster Abstracts (ID 10908)
07:30 - 11:30 | Presenting Author(s): Jonathan W Riess
- Abstract
- Presentation
Abstract not provided
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MA 02 - Emerging Targets (ID 656)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Clinical Design, Statistics and Clinical Trials
- Presentations: 1
- Moderators:Ravi Salgia, Shun Lu
- Coordinates: 10/16/2017, 11:00 - 12:30, Room 511 + 512
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MA 02.11 - A Phase I Trial of Erlotinib and Onalespib in EGFR-mutant NSCLC: Focus on EGFR Exon 20 Insertions (ID 9046)
11:00 - 12:30 | Presenting Author(s): Jonathan W Riess
- Abstract
- Presentation
Background:
Onalespib (AT13387) is a non-ansamycin small molecule that inhibits heat shock protein-90 (Hsp90). Hsp90 inhibitors (Hsp90i) preferentially degrade overexpressed and mutated oncoproteins including those that mediate resistance to EGFR-TKIs. Previous Hsp90i studies demonstrated activity in EGFR-mutant NSCLC including EGFR Exon 20 insertions (EGFRex20ins) - uncommon EGFR mutations typically refractory to 1[st] and 2[nd] generation EGFR-TKIs. A phase I study of onalespib plus erlotinib was conducted to determine the MTD, DLT, RP2D, pharmacokinetics (PK) and preliminary antitumor activity for a planned phase 2 trial in EGFR-mutant NSCLC including EGFRex20ins.
Method:
Using a 3 + 3, dose escalation design, onalespib was examined at 2 dose levels (DL) from 150 (DL0) to 120 (DL-1) mg/m[2] IV weekly (D1, D8, D15 on a q28 day cycle). Daily erlotinib was given at 150 mg at both DL. Key eligibility: NSCLC with EGFR activating mutation including EGFRex20ins, age ≥ 18, ECOG PS≤2, acceptable organ function, and ≥1 systemic therapy for advanced disease (platinum-based chemotherapy for EGFRex20ins and EGFR-TKI for other EGFR-mutations). Plasma for PK and ctDNA for next-generation sequencing of ~70 cancer related genes was collected at relevant timepoints.
Result:
9 pts have been treated on 2 DL (3 DL0, 6 DL-1). Pt characteristics: median age 65, M/F (2/7), ECOG PS 0-1 (4/5), EGFRex20ins (8), EGFR E19del (1). 7 pts completed ≥1 cycle. Two DLTs (grade (Gr) 3 maculopapular rash and Gr 3 hypophosphatemia) occurred in DL0. Common drug-related adverse events (AE) of any Gr were diarrhea (100%) and rash (44%), fatigue (55%), increased bilirubin (22%), nausea (44%) and vomiting (33%). Drug-related Gr 3 AEs were diarrhea (55%), maculopapular rash (11%) and hypophosphatemia (11%). At the planned 2-month evaluation, 5 pts had SD, 3 PD, and 1 had withdrawn for toxicity. Of the 5 pts continuing, 2 had SD and 1 PD at the 4-month evaluation. Kaplan-Meier estimate on therapy without progression at the second evaluation is 30% (95% CI: 10 to 87%).
Conclusion:
In patients with EGFR-mutant NSCLC, onalespib plus erlotinib is feasible, tolerable and demonstrates disease control in EGFRex20ins, thereby addressing a key unmet need in NSCLC. The RP2D is erlotinib 150 mg PO daily and onalespib 120 mg/m[2] weekly (D1, D8, D15 q28days). Diarrhea was the most common AE, and generally manageable with supportive care and dose reduction to DL-1. Updated results including PK as well as ctDNA for EGFR-mutation and relevant bypass tracts mediating EGFR-TKI resistance will be presented.
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P2.04 - Clinical Design, Statistics and Clinical Trials (ID 705)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Clinical Design, Statistics and Clinical Trials
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.04-010 - Afatinib in Combination with Pembrolizumab in Patients with Stage IIIB/IV Squamous Cell Carcinoma (SCC) of the Lung (ID 9425)
09:30 - 16:00 | Presenting Author(s): Jonathan W Riess
- Abstract
Background:
Afatinib has demonstrated progression-free survival (PFS) and overall survival (OS) improvements in patients with squamous cell carcinoma (SCC) of the lung; pembrolizumab also showed encouraging PFS/OS in lung SCC. Afatinib is a selective and irreversible ErbB family blocker that effectively inhibits signaling from all homo- and heterodimers formed by ErbB family members EGFR (ErbB1), HER2 (ErbB2), ErbB3, and ErbB4. Pembrolizumab is a humanized immunoglobulin G4 (IgG4) monoclonal antibody with high affinity and potent receptor-blocking activity for the programmed cell death 1 (PD-1) receptor. Concurrent inhibition of PD-1 and EGFR pathways represents a rational and promising approach for EGFR-driven tumors such as SCC of the lung, to increase the rate and duration of response, and delay the development of resistance, as single-agent efficacy can be moderate and more treatment options are needed. This trial assesses the efficacy and safety of afatinib in combination with pembrolizumab in patients with locally advanced or metastatic squamous non-small cell lung cancer (NSCLC) who progressed during or after first-line platinum-based treatment.
Method:
Trial design: Study 1200.283 (NCT03157089. LUX-Lung IO / Keynote 497) is a phase II, open-label, non-randomized single-arm study. Eligible patients have locally advanced or metastatic squamous NSCLC and have progressed during/after first-line platinum-based chemotherapy. Patients must have adequate organ function and ECOG PS 0/1. Prior treatment with immune checkpoint inhibitors or EGFR targeted therapy is prohibited. A safety run-in will be performed using afatinib once daily (starting dose 40 mg) in combination with pembrolizumab, (200 mg fixed dose once every 3 weeks, administered intravenously) to assess the safety profile and confirm the recommended Phase II dose (RP2D). In the main part of the trial, afatinib at the RP2D, in combination with pembrolizumab, may be continued for a maximum of 35 cycles (~2 years). After study completion, further therapy will be decided by the investigator and may include afatinib. Dose reduction of afatinib to 30 mg or 20 mg will be permitted in the case of adverse events. The primary endpoint is investigator assessed objective response (complete response [CR] or partial response [PR] according to RECIST v1.1). Secondary/further endpoints are disease control (CR, PR, or stable disease), duration of objective response, PFS, OS, tumor shrinkage, RP2D, and pharmacokinetics. Exploratory biomarker analysis will also be performed. This study will be conducted in the US, Spain, France, Korea, and Turkey, and will open for enrollment in September 2017; target enrollment is 50-60 patients.
Result:
Not applicable
Conclusion:
Not applicable
