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Ramon W Mohanlal
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-11 - Quality of Life in NSCLC Patients Treated with Docetaxel and Either Plinabulin or Pegfilgrastim for Prevention of Neutropenia (Now Available) (ID 2513)
09:45 - 18:00 | Author(s): Ramon W Mohanlal
- Abstract
Background
Plinabulin is a novel small molecule, in development for the prevention of chemotherapy-induced-neutropenia (CIN). Plinabulin has anticancer activity and is separately developed through a global 3 trial (NCT02504489) for 2nd and 3rd line NSCLC patients. In contrast to pegfilgrastim, plinabulin does not produce bone pain, a chief complaint of patients taking pegfilgrastim. As part of the Phase 2 CIN protocol we measured patient quality of life (QoL) comparing pegfilgrastim and plinabulin.
Method
In the Phase 2 portion of the Phase 2/3 Study 105 (NCT03102606), patients received docetaxel 75 mg/ m2 on Day 1, and were randomly assigned to either one of three plinabulin doses: 5 mg/m2 (n=14), 10 mg/m2 (n=13), 20 mg/m2 (n=14) mg/m2 on Day 1 (30 minutes after docetaxel infusion) over 4 cycles or no plinabulin and pegfilgrastim on Day 2. QoL was assessed with the validated health related questionnaires EORTC QLQ-C30 on D1 of each of the 4 cycles prior to study drug, and end of treatment. Day 1 Cycle 1 was baseline QoL. The data was analyzed using the standard methodology from the EORTC QLQ-C30 scoring manual which converts the 30 questions into three categories: global health status / QoL, functional scales, and symptom scales. The individual scores as well as the combined quality of life status, functional scales, symptoms scales, and the overall summary EORTC QLQ-C30 scores were analyzed. The difference between the treatment arms was analyzed using a linear mixed model for repeated measures with baseline and treatment arms as covariates.
Result
Plinabulin 20mg/m2 (clinically effective dose for CIN) demonstrated a significant improvement in QoL over 4 treatment cycles in three of the four parameters measured: global health status (p-value >0.0001), symptom scales (p-value 0.0093), and summary score (p-value 0.0195). In addition, there were significant improvements in three symptom scales: fatigue (p-value 0.0317), pain (p-value 0.0274), and insomnia (p-value 0.05).
Conclusion
Although these results are preliminary, they are significant and indicate improvements in QoL in patients being treated for advanced NSCLC with docetaxel and the addition of plinabulin for CIN prevention. This trend will be further investigated in ongoing Phase 3 trials for both NSCLC (NCT02504489), and CIN (NCT03102606 and NCT03294577).
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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 | Presenting Author(s): Ramon W Mohanlal
- 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.
