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Goetz H. Kloecker
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P1.18 - Treatment of Locoregional Disease - NSCLC (ID 190)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.18-05 - ChemoXRT W/ Consolidation Pembrolizumab in Unresectable Stage III NSCLC: Long-Term Survival Update and Analysis of Post-Progression Therapy (Now Available) (ID 2765)
09:45 - 18:00 | Author(s): Goetz H. Kloecker
- Abstract
Background
Consolidation PD-1/PD-L1 inhibition following chemoradiation is a new standard of care for patients with stage III NSCLC. 3-year survival rates in patients receiving consolidation PD-1/PD-L1 have not been previously reported. In addition, the response to subsequent chemotherapy or immunotherapy in patients who experienced disease progression following consolidation PD-1/PD-L1 has also not been previously reported.
Method
This is a phase II, single-arm, multi-center trial of consolidation pembrolizumab 200mg IV every 3 weeks for up to a year following concurrent chemoradiation in patients with unresectable stage III NSCLC. This analysis provides the first-ever report of 3-year overall survival (OS) estimates with consolidation PD-1. In addition, treatment details for patients who experienced progression of disease on or after consolidation pembrolizumab are described.
Result
Median follow is 31.1 months (range 1.2-42.4). Median OS is 35.8 months (95% CI, 24.2 -not estimable). One, two, and three-year OS estimates are 81.1%, 62%, and 49.5%. Of 37 patients reported to have progressive disease (PD), subsequent treatment data were available for 35. Twenty-four received additional systemic therapy, and 11 received no subsequent systemic treatment. Fifteen experienced PD during pembrolizumab, 18 after pembrolizumab (and 4 had missing data). The best response to any systemic therapy (n=24) was 3 partial responses (PR), 9 stable disease (SD), and 12 PD. Chemotherapy was given to 21 patients and 1 patient each received erlotinib, ponatinib, and an investigational agent. Best response to chemo was 2 PR, 6 SD, and 13 PD. 11 patients received pemetrexed with 2 SD and 9 PD; 6 patients received a single agent taxane with 1 SD and 5 PD. 5 patients received combination therapy with 1 PR, 3 SD, and 1 PD. 3 patients received gemcitabine with 1 PR and 2 PD. 6 of 24 patients received subsequent PD-1 or PD-L1 inhibitors; the best response to immunotherapy was 1 PR and 5 PD. The PR was a patient who had completed pembro consolidation 14 months prior to PD and subsequently was retreated with pembro at the time of biopsy-proven recurrence (PD-L1 TPS was 90%). He responded after 3 cycles of pembro and has maintained this response for 13+ cycles.
Conclusion
The 3-year OS estimate indicates that nearly half of all patients treated with consolidation pembrolizumab may be long-term survivors. For patients with disease progression after consolidation pembrolizumab, response rates with chemotherapy are similar to what is expected in the 2nd line setting with 38% experiencing disease control for a period of time. Only 1 of 6 patients re-challenged with a checkpoint inhibitor responded, but this patient has maintained a durable response lasting 13+ cycles.
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P2.01 - Advanced NSCLC (ID 159)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.01-23 - DUBLIN-3, a Phase (Ph) III Trial Comparing the Plinabulin (P)/Docetaxel(D) Combination with D Alone in Stage IIIb/IV NSCLC (Now Available) (ID 476)
10:15 - 18:15 | Author(s): Goetz H. Kloecker
- Abstract
Background
In 2018, practice patterns changed in untreated metastatic NSCLC, as platinum-based chemotherapy (Chemo) started to be combined with pembrolizumab. Prior to 2018, checkpoint inhibitors (C-I) were given sequentially with Chemo. In C-I refractory metastatic NSCLC, single agent D is standard of care. Although effective, D induces AEs (Neutropenia (N) that may require dose reduction to sub-therapeutic levels. The addition of Plinabulin (P) to D (D+P) reduced D-induced grade 4 (Gr4) N (frequency of 33% vs 5% for D vs D+P; p<0.0003) and thrombocytopenia (P<0.02) vs D alone (Blayney ASH 2018; IASLC 2018) in Ph 2. Importantly, P added to D improved median overall-survival (OS) with 4.6-month, and duration of response (DoR) with 1-year (p<0.05) vs D alone (Mohanlal ASCO-SITC 2017) in pts with a measurable lesion (per RECIST 1.1) located in the lung. P induces Dendritic Cell (DC) maturation and CD40 upregulation and facilitates DC-dependent T-cell proliferation in an antigen (Ag) specific manner (Lloyd AACR 2016). Therefore, P is predicted to be the most effective in a setting that harbors novel Ags, that can stimulate the immune system. Subclonal lung lesions can induce novel Ags (De Bruin Science 2014), but clonal lung lesions can also harbor Ags that can stimulate the immune system, as long as immune tolerance is not yet developed. There is a high concordance in mutation status (thus Ags) between clonal primary and metastatic lesions in NSCLC (Sherwood J Exp & Clin Canc Res 2015), but the distant lesions had more time to induce immune tolerance development. Hence, we required the presence of measurable lesion present in the lung in DUBLIN-3. We combined P with D since D can release Ags which in turn can be presented by P-modulated DCs to cytotoxic CD8 T-cells.
Method
DUBLIN-3 (NCT02504489), is an ongoing global PhIII study in EGFR wild-type advanced or metastatic NSCLC pts (target n=554) receiving 2nd- or 3rd-line systemic therapy with D+P or D in a 1:1 ratio. The primary endpoint is OS. Key secondary endpoints are incidence of Gr 4 N on day 8 of Cycle 1, D dose modification due to N, QoL (EORTC QLQ-C30), ORR, PFS, and DoR. The study is single-blinded (for pts) to more reliable allow for QoL assessments. Pts must have at least one measurable lesion located in the lung and must have failed a prior platinum-based regimen. Prior PD1/PD-L1 use is allowed. A pre-specified first Interim Analysis (IA) occurred at reaching ~150 events and a second pre-specified IA is to occur at ~ 300 events.
Result
~400 patients have been enrolled to date with more than 200 events achieved. Based on the data at the 1st IA, the study will continue, unmodified, to the 2nd IA.
Conclusion
The D+P combination holds the promise of a novel 2nd or 3rd line treatment option with superior efficacy and safety over D alone. The 2nd IA of DUBLIN-3 is expected to occur later in 2019.
