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Israel Lowy
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EP1.04 - Immuno-oncology (ID 194)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.04-15 - NSCLC Response Determinants to Chemoimmunotherapy: Deep Profiling of Tumors Following Neoadjuvant Cemiplimab and Chemotherapy (Now Available) (ID 1021)
08:00 - 18:00 | Author(s): Israel Lowy
- Abstract
Background
Clinical trials have demonstrated synergistic effects of combination chemoimmunotherapy in patients with locally advanced and metastatic non-small cell lung cancer (NSCLC), however, our understanding is limited as to why and for whom PD-1 blockade with or without chemotherapy is effective, as is our understanding of the mechanism of synergy between these therapies.
While most patients with resectable NSCLC receive neoadjuvant or adjuvant chemotherapy, this intervention only changes the natural course of disease for ~5% of patients. Early studies have demonstrated major pathologic responses to neoadjuvant immunotherapy ± chemotherapy.
Method
To investigate the immunodynamic effect of PD-1 blockade and chemotherapy, and identify potentially more effective immune modifying targets or combinations, we will use novel immunophenotyping platforms to characterize the effect of this combination on the tumor. This trial will enroll 52 patients with Stage Ib-IIIa NSCLC into three cohorts receiving 2 cycles of 1) platinum-doublet chemotherapy, 2) the PD-1 antibody cemiplimab, or 3) combination chemoimmunotherapy. Following surgery, patients will receive additional adjuvant chemoimmunotherapy; in total all patients will receive 4 cycles of standard platinum-doublet chemotherapy and 8 cycles of cemiplimab. All patients will undergo pre-treatment biopsies of their tumor, and blood will be collected at 6 time-points before and after surgery.
The primary endpoint for this clinical trial is major pathologic response, defined as ≤10% viable tumor within resection. Secondary endpoints include: delay of surgery, disease-free survival, overall response rate, overall survival, measurement of adverse events, and change in CD8 T-cell infiltration.
Exploratory endpoints include in-depth analysis of the pre-treatment tumor biopsies and post-treatment surgical specimens, and paired blood. We will characterize proteomic and transcriptomic changes in the stromal and immune compartment of tumors at the histologic level using a multiplexed ion-beam imaging (MIBI)—a novel multiplex immunohistochemistry platform capable of analyzing >50 markers on a single section of tissue—and at the single-cell level using Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITEseq), a novel platform combining the proteomic data-potential of mass cytometry (CyTOF) and the transcriptomic data-potential of single cell RNA sequencing including TCR sequencing. Feasibility of this multi-pronged approach has been demonstrated on untreated NSCLC (unpublished data, submitted as abstract to WCLC by our group).
To probe for biomarkers correlating with response or resistance to therapy, we will perform unbiased analysis of peripheral blood lymphoid and myeloid populations by CyTOF, and measure nearly 100 soluble factors in serum using Olink.
Result
This trial opened to accrual April 2019.
Conclusion
Section not applicable.
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P2.01 - Advanced NSCLC (ID 159)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.01-01 - Cemiplimab, a Human PD-1 Monoclonal Antibody, Versus Chemotherapy in First-Line Treatment of Advanced NSCLC with PD-L1 ≥50% (ID 1380)
10:15 - 18:15 | Author(s): Israel Lowy
- Abstract
Background
Most patients (pts) with non-small cell lung cancer (NSCLC) present with advanced disease at diagnosis. Despite initial response to platinum-based doublet chemotherapy, an established first-line treatment for pts with advanced NSCLC whose tumours do not have EGFR, ALK, or ROS 1 mutations, pts often progress and require additional treatment options. In recent years, anti-programmed death-1 (anti–PD-1) therapies have emerged as an effective treatment option for advanced NSCLC, potentially allowing some patients with PD-L1 expression ≥50% to avoid chemotherapy. However, there is currently only one PD-1 inhibitor approved as monotherapy in first-line treatment of NSCLC. In a Phase 1 trial of pts with advanced malignancies, including NSCLC, cemiplimab exhibited anti-tumour activity with a safety profile similar to those described for other anti–PD-1 agents. Cemiplimab-rwlc is the only Food and Drug Administration-approved treatment for patients with advanced cutaneous squamous cell carcinoma.
Method
This is a randomised (1:1), multicentre, open-label, Phase 3 study of cemiplimab versus platinum‑based doublet chemotherapy in systemic treatment‑naïve pts (≥18 years) with stage IIIB, IIIC or IV squamous or non‑squamous NSCLC whose tumours express PD‑L1 in ≥50% of tumour cells (NCT03088540). Pts will be stratified by histology and geographic region. Pts will receive cemiplimab 350 mg every 3 weeks intravenously (for up to 108 weeks) or 4–6 cycles chemotherapy with (i) paclitaxel + cisplatin or carboplatin, (ii) pemetrexed + cisplatin or carboplatin with or without pemetrexed maintenance, (iii) or gemcitabine + cisplatin or carboplatin. Crossover from chemotherapy to cemiplimab and addition of chemotherapy to cemiplimab at the time of disease progression is allowed. The primary objective is to evaluate progression-free survival (PFS) as determined by blinded independent review committee. Key secondary objectives include assessment of overall survival and objective response rate. An independent data monitoring committee will monitor safety data during study conduct.
Result
Section not applicable
Conclusion
Section not applicable
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P2.01-26 - EMPOWER-Lung 3: Phase 3 Study of Combinations of Cemiplimab and Chemotherapy in First-Line Treatment of Advanced NSCLC (ID 2173)
10:15 - 18:15 | Author(s): Israel Lowy
- Abstract
Background
Most patients (pts) with non-small cell lung cancer (NSCLC) present with advanced disease at the time of diagnosis. Until recently, platinum-based doublet chemotherapy regimens were the standard of care first-line treatment for pts with advanced NSCLC whose tumors lack an EGFR, ALK, or ROS1 mutation. Despite chemotherapy, patients with metastatic NSCLC had a median overall survival (OS) of 8 to 12 months and a 5-year survival rate of approximately 18%. With the introduction of programmed cell death-1 (PD-1) inhibitors to NSCLC, this prognosis has improved. Cemiplimab, a human PD-1 monoclonal antibody, has exhibited antitumor activity and safety in a Phase 1 trial of advanced malignancies including NSCLC and was approved recently in the US as cemiplimab-rwlc for advanced cutaneous squamous cell carcinoma (CSCC). Based on their unique modes of action, combining cemiplimab with platinum‑based chemotherapy has the potential for a synergistic effect in pts with advanced NSCLC of both histologies and irrespective of PD-L1 expression.
Method
EMPOWER-lung 3 is a randomised, global, two-part, Phase 3 study of first-line treatment of pts with advanced squamous or non-squamous NSCLC (NCT03409614). Part 1, as previously described (IASLC 19th WCLC; Abstract 13347), is open-label and aims to describe the efficacy and safety of combinations of cemiplimab, ipilimumab, and platinum-based doublet chemotherapy in pts whose tumors express PD-L1 in <50% of the tumor cells. The updated primary endpoint of Part 1 is objective response rate.
Here we introduce the recently added Part 2. This part is double-blinded and will compare the efficacy and safety of cemiplimab versus placebo, both in combination with investigator’s choice of standard chemotherapy, in all pts irrespective of PD-L1 expression status. Chemotherapy options include: paclitaxel + carboplatin or cisplatin for squamous cell NSCLC and pemetrexed + carboplatin or cisplatin for non-squamous NSCLC. The investigator may choose from one of these regimens provided that it is consistent with the local standard-of-care. Pts will be randomized (2:1) to cemiplimab 350 mg Q3W plus up to four cycles of chemotherapy or placebo Q3W plus up to four cycles of chemotherapy. Pts will be stratified by histology and PD-L1 expression levels. The co-primary endpoints for Part 2 are OS and progression-free survival (PFS).
Result
Section not applicable
Conclusion
Section not applicable
