Virtual Library
Start Your Search
S. He
Author of
-
+
P1.04 - Clinical Design, Statistics and Clinical Trials (ID 690)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Clinical Design, Statistics and Clinical Trials
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
-
+
P1.04-001 - Osimertinib with Ramucirumab or Necitumumab in Advanced T790M-positive EGFR-Mutant NSCLC: Preliminary Ph1 Study Results (ID 7940)
09:30 - 09:30 | Author(s): S. He
- Abstract
Background:
Combination studies of a first- or second-generation EGFR tyrosine kinase inhibitor (TKI) and either a VEGF or EGFR-targeting monoclonal antibody have recently shown promising clinical results in EGFR-mutant non-small cell lung cancer (NSCLC) patients. The preliminary safety results from the phase 1 study JVDL (NCT02789345), combining third-generation EGFR TKI osimertinib (Osi) with human IgG1 monoclonal antibodies ramucirumab (Ram) or necitumumab (Neci), are reported.
Method:
Eligible pts naïve to third-generation EGFR TKI therapy with advanced EGFR T790M-positive NSCLC who progressed after initial EGFR TKI therapy were enrolled. In the dose-finding portion, following a dose de-escalation 3+3 design, patients received daily oral Osi (80 mg) and either 10 mg/kg intravenous (IV) Ram on day 1 (D1) every two weeks (Q2W), or 800 mg (IV) Neci on D1 and D8 Q3W. Primary objective of the study is to assess the safety and tolerability of Ram or Neci combined with Osi, and secondary objectives include preliminary evaluation of efficacy.
Result:
As of data cutoff on 09-May-2017, 7 pts were treated in the completed dose-finding portion: 3 pts with Ram+Osi (Arm A) and 4 pts (1 non-evaluable and replaced) with Neci+Osi (Arm B). No DLTs were observed in either arm, and the initial dose level became the recommended dose for expansion cohort. After the DLT observation period was complete, the only Grade ≥3 (Gr≥3) treatment-related adverse event (TRAE) was dermatitis acneiform (Arm B), with one unrelated Gr≥3 treatment-emergent AE (TEAE) of increased lipase (Arm B) and one serious AE of Gr2 diverticulitis (unrelated to study treatment) (Arm A). Expansion cohort A of Ram+Osi is fully enrolled with 22 pts. Safety data were available for 18 out of 22 cohort A patients. Gr≥3 TEAEs were reported in 4 patients, including dyspnea (unrelated [n=1]), decreased appetite (unrelated [n=1]), and hypertension (related [n=2]). Three patients reported serious adverse events (none related to study treatment): Gr3 dyspnea and Gr2 pyrexia, Gr2 dyspnea, and Gr2 urinary tract infection. No death was reported in patients in the dose-finding portion, and one death unrelated to study treatment was reported in the expansion cohort.
Conclusion:
No DLTs were observed and no unexpected safety signals were seen to date. The recommended dose for expansion cohort was the initial dose level of 10 mg/kg ramucirumab IV Q2W with oral 80 mg osimertinib. Additional safety and efficacy observation for the combination of Ram+Osi is ongoing, and will be presented at the meeting.
-
+
P2.01 - Advanced NSCLC (ID 618)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:00 - 16:00, Exhibit Hall (Hall B + C)
-
+
P2.01-040 - Pemetrexed plus Platinum Chemotherapy with or Without Immunotherapy in Non-Squamous NSCLC: Descriptive Safety Analysis (ID 9882)
09:00 - 09:00 | Author(s): S. He
- Abstract
Background:
Pemetrexed/platinum doublet chemotherapy is under investigation in combination with various immunotherapeutic agents (atezolizumab, nivolumab, pembrolizumab) for treatment of advanced non-squamous (NS) NSCLC, with reported durable efficacy and tolerability in early-phase clinical trials. Recently, the combination of pembrolizumab plus pemetrexed/carboplatin received US FDA accelerated approval as front-line treatment for patients with this disease based on the data from a randomized phase II trial, KEYNOTE-021 Cohort G. We present our descriptive analysis of the safety outcomes of pemetrexed (combination) from 3 randomized trials (PRONOUNCE, PARAMOUNT, and KEYNOTE-021 Cohort G).
Method:
Criteria for selection of studies included randomized trials, first-line treatment for NS NSCLC patients with pemetrexed-based combination treatment, with or without immunotherapy, followed by continuation maintenance (at least one arm or cohort). Parameters such as baseline characteristics, dose exposure, and safety outcomes (AE, SAE, death, dose delay or discontinuation, AE management, and hospitalization) are compared.
Result:
Using data from PRONOUNCE (n=182), PARAMOUNT (n=359), and KEYNOTE-021 (Cohort G, n=123) we describe the safety outcomes of pemetrexed/platinum-based combination therapy. Median age of patients from 3 studies was 61- 66 years. The majority of patients in PRONOUNCE and PARAMOUNT were male, whereas female in KEYNOTE-021G; with ECOG PS 1, and adenocarcinoma. The number of patients who completed 4 cycles of induction were 70.8%, 67.8%, 88.1%, and 71.0% in PRONOUNCE, PARAMOUNT, and KEYNOTE 021G Combo arm and Pem+Cb only arm, with median number of treatment cycles of 6, 8, 11, 8, respectively. All pemetrexed combinations with/without immunotherapy had a reasonable and manageable safety profile in our analysis (Table 1). Figure 1
Conclusion:
This analysis provides a comprehensive safety overview of pemetrexed/platinum with or without immunotherapy in NS NSCLC. Ongoing phase 3 randomized studies of the combination could further inform the safety/efficacy of pemetrexed/platinum plus immunotherapy.
