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Lei Feng
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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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OA02.06 - A Phase II Trial of Poziotinib in EGFR and HER2 exon 20 Mutant Non-Small Cell Lung Cancer (NSCLC) (ID 14277)
11:25 - 11:35 | Author(s): Lei Feng
- Abstract
- Presentation
Background
Insertions/mutations in exon 20 of EGFR or HER2 occur in ~3% of all lung adenocarcinomas. These alterations are characterized by primary resistance to tyrosine kinase inhibitors (TKIs) with response rates of <12%. We previously showed that exon 20 insertions restrict the size of drug-binding pocket, limiting binding of most available TKIs. However, poziotinib can potentially circumvent these steric changes due to its smaller, flexible structure and is a potent inhibitor of EGFR and HER2 exon 20 mutants (Robichaux et al. Nat Med, 2018). Herein, we report the results of an investigator-initiated study of poziotinib in EGFR and HER2 exon 20 mutant NSCLC (NCT03066206).
a9ded1e5ce5d75814730bb4caaf49419 Method
Patients ≥18yrs with metastatic NSCLC bearing mutations/insertions in EGFR or HER2 exon 20 (except EGFR T790M) were eligible. Unlimited prior systemic and targeted therapies were permitted. Poziotinib 16mg PO daily was administered until progression, death, or withdrawal. The primary endpoint was objective response rate (ORR) based on RECIST v1.1. Response was evaluated every eight weeks. A Bayesian design was used with a plan to enroll patients in cohorts of 10 and to terminate the study if ORR was ≤20%. Secondary endpoints included DCR, PFS, OS and safety
4c3880bb027f159e801041b1021e88e8 Result
As of May 3, 2018, the planned EGFR cohort of 50 patients was fully enrolled, and 40 patients were evaluated for response. 65.1% of patients had received at least two prior lines of therapy for metastatic disease. 60% of patients had ≥grade 3 adverse events; most common were skin-rash (27.5%) and diarrhea (12.5%). 45.0% of patients required dose reduction to 12mg, while 17.5% required dose reduction to 8mg. One patient stopped treatment due to grade 3 skin rash. ORR at eight weeks was 58% (95%-CI 40.9-73.0) and the DCR was 90% (95%-CI 76.3-97.2). Among 23 patients who achieved partial response, 15 responses were confirmed with subsequent scans, five responses were unconfirmed, and three patients are pending confirmation. Responses were observed in 8/13 (62%) patients that were previously treated with TKI. Median PFS was 5.6mo (95%-CI 5.06-NA). Furthermore, 13 patients were enrolled in HER2 cohort. Toxicities were similar to EGFR cohort except one case of grade 5 pneumonitis, assessed to be possibly drug related. Twelve patients were evaluated for response with ORR of 50% (95% CI 21.1-78.9) at eight weeks and DCR of 83%.
8eea62084ca7e541d918e823422bd82e Conclusion
In heavily pre-treated population with EGFR and HER2 exon 20 mutant NSCLC, poziotinib demonstrated encouraging antitumor activity in both TKI-naive and -refractory patients, and manageable toxicity profile.
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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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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P2.04-25 - Randomized Clinical Trial Comparing Immunotherapy Plus SABR (I-SABR) Versus SABR Alone for Early Stage NSCLC (ID 12620)
16:45 - 18:00 | Author(s): Lei Feng
- Abstract
Background
Section not applicable
Stereotactic ablative radiotherapy (SABR), which delivers high biologically effective radiation doses, can kill cancer cells, release tumor-associated antigens, and activate tumor-specific T cells, thereby functioning as a cancer-specific vaccine in situ. The combination of the immune-triggering effects of ionizing radiation with immune check point PD-1inhibitor may leverage the effects of radiotherapy, transforming what was once considered a local therapy to a novel systemic treatment. Further, the combined effects of local tumor control plus systemic control may improve cure rate in early stage NSCLC.
a9ded1e5ce5d75814730bb4caaf49419 Method
Section not applicable
This is a randomized phase II trial (NCT03110978) designed to study SABR (biological effective dose >100 Gy) with or without concurrent and adjuvant Nivolumab for total of 7 doses in early stage or isolated recurrent NSCLC. Inclusion criteria: stage I disease (tumor size ≤5 cm, N0M0) OR selected cases of stage IIa disease (tumor size >5 cm but ≤7 cm, N0M0), including multiple primary tumors, OR isolated lung-parenchymal recurrent or persistent NSCLC suitable for SABR. Tumor tissue /blood/stool samples will be collected before/during/after treatment and at the time of recurrence. Primary endpoints: Event-free survival (EFS), defined as local recurrence, regional recurrence, distant metastasis, secondary malignancy and death; secondary endpoints: overall survival; toxicity; exploratory analyses of potential predictive markers and immunologic mechanisms of action.
Statistical design: It is considered clinically significant with a decrease of the 4-year cumulative event rate from 46% to 23%. Assuming a one-sided type I error rate of 0.05, an accrual rate of 3.5 patients per month, and an additional 20 months of follow-up, a study with 70 patients in each arm will have 85% power to detect an improvement of 23% in 4-year EFS rate. One interim analysis will be done to allow early termination of the trial should evidence at that time reveal that I-SABR is superior to SABR-only or that no difference is found between the two treatment arms.
4c3880bb027f159e801041b1021e88e8 Result
Section not applicable
Up to April 30, 2018, 36 of planned 140 patients have been enrolled.
8eea62084ca7e541d918e823422bd82e Conclusion
Section not applicable
Phase II randomized clinical trial comparing immunotherapy plus Stereotactic Ablative Radiotherapy (I-SABR) versus SABR Alone for stage I, selected stage IIa or isolated lung parenchymal recurrent Non-Small Cell Lung Cancer is ongoing and met with anticipated enrolment rate.
6f8b794f3246b0c1e1780bb4d4d5dc53
