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James Spicer
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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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P1.13-17 - Multicentre Phase II Trial of First-Line Afatinib in Patients with Suspected/Confirmed EGFR Mutant NSCLC: ctDNA & Long-Term Efficacy (ID 11908)
16:45 - 18:00 | Author(s): James Spicer
- Abstract
Background
Efficacy of afatinib in EGFR mutant patients with comorbidities or those with suspected EGFR mutations unfit for chemotherapy is poorly explored. We evaluated afatinib in this population, with serial plasma ctDNA to investigate the role of molecular EGFR genotyping and monitoring.
a9ded1e5ce5d75814730bb4caaf49419 Method
Phase-II trial enrolled NSCLC patients with comorbidities precluding chemotherapy, and either (i) EGFR-mutation, PS 0-3, or (ii) suspected EGFR-mutation (tissue unavailable/failed genotyping), never/former-light smoker, adenocarcinoma, and PS 0-2. Afatinib (40mg daily) given until progression/toxicity. Blood samples obtained at baseline and 12-weekly until discontinuation; plasma ctDNA performed using InVisionSeq™ (amplicon-based NGS).
4c3880bb027f159e801041b1021e88e8 Result
39 patients recruited (14 UK centres). Median age 72 years; 27 PS 0-1/12 PS 2-3. 21 patients (54%) had known tissue EGFR-mutations. Additional 8 patients with unknown tissue status (8/17;47%), were ctDNA EGFR-mutant, making 74% EGFR-mutant in total (29/39). Combined tissue and ctDNA data identified 21 patients with common mutations (exon 19/L858R), 8 with rare mutations (exon 18/20), and 10 suspected only. Corresponding median PFS of these cohorts were 10.2/3.9/5.3 months, with 6-month PFS of 71/38/50% all exceeding the 30% target; median OS were 24.8/5.7/11.4 months (p<0.001). Therefore, all patient groups benefitted; known EGFR-mutants having best outcomes. In April 2018, 5/39 patients survived >36 months, including 4/39 progression-free (median follow-up 33 months, maximum 55). Patients with ctDNA mutation clearance during afatinib treatment had substantially improved outcomes compared to those without clearance (Figure). 40% (4/10) of mutant cases who discontinued after 3 cycles because of progressive disease developed an exon 20 EGFR-mutation.
8eea62084ca7e541d918e823422bd82e Conclusion
Patients unsuitable for chemotherapy with confirmed/suspected EGFR-mutations by tissue or ctDNA benefit from afatinib. Serial ctDNA is a potentially useful stratification and monitoring tool; amplicon-based ctDNA analysis can identify EGFR mutations when tissue is unavailable. Exon 20 mutations were observed at acquired resistance. ctDNA clearance during afatinib treatment is strongly associated with better PFS/OS.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P2.04 - Immunooncology (Not CME Accredited Session) (ID 953)
- 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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P2.04-27 - Ph II Study of Oral Selective AXL Inhibitor Bemcentinib (BGB324) in Combination with Pembrolizumab in Patients with Advanced NSCLC (ID 14307)
16:45 - 18:00 | Author(s): James Spicer
- Abstract
Background
Bemcentinib (BGB324) is a first-in-class, highly selective oral inhibitor of the AXL tyrosine kinase currently in phase II clinical development across several cancer types. AXL overexpression has been observed in pts failing anti-PD-1 therapy in several cancers whereas AXL inhibition via bemcentinib has shown synergistic effect with checkpoint blockade in pre-clinical models of NSCLC.
In pts with advanced, pre-treated NSCLC, bemcentinib monotherapy led to disease stabilisation in 2 out of 8 pts including evidence of tumour reduction. Combination therapy of bemcentinib with EGFR inhibition indicated the potential of AXL blockade to reverse resistance to targeted therapy in advanced EGFR therapy resistant NSCLC. Evidence of immune activation following bemcentinib monotherapy was observed in AML patients.
This open label, single-arm, two-stage Phase 2 study was designed to test whether AXL inhibition may increase the efficacy of pembrolizumab in patients with advanced, previously treated adenocarcinoma of the lung.
a9ded1e5ce5d75814730bb4caaf49419 Method
Patients with documented Stage IV adenocarcinoma of the lung who had progressed on previous platinum chemotherapy and – if applicable – at least one line of licensed EGFR or ALK targeted therapy, received 200 mg/d bemcentinib po and 200 mg/q3wk pembrolizumab iv. Patients were required to consent to a fresh pre-treatment biopsy. Tumour assessments were done 9-weekly. The primary endpoint was ORR. Tumour biopsies were analysed for PD-L1 and AXL as well as immune cell populations. Plasma protein biomarker levels were measured using the DiscoveryMap v3.3 panel (Myriad RBM) in patients pre-dose and at C2D1.
4c3880bb027f159e801041b1021e88e8 Result
As of time of writing, the study had fully recruited its first stage. Of 24 patients enrolled, 14 were ongoing. 6 of 10 patients who had reached their first scan showed evidence of tumour shrinkage including 3 pts with partial responses in their target lesions. 2 patients had stable disease. There were no grade 4 treatment-related events. Dose reduction from 200 to 100 mg/d of bemcentinib as a consequence of adverse events was required in 12% of patients. Correlation of AXL and PD-L1 expression with response was evaluated. Soluble AXL plasma levels were increased following one cycle of treatment indicative of target engagement.
8eea62084ca7e541d918e823422bd82e Conclusion
A preliminary analysis of response to combination treatment during the first stage of this study as well as biomarker correlation will be presented at the meeting. Clinical trial information: NCT03184571
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