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L. Paz-Ares
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HOD 03 - Highlights of the Previous Day: Treatment of Advanced, Localized and LocoRegional Disease and Small Cell, Thymoma, Mesothelioma (ID 242)
- Event: WCLC 2015
- Type: Highlights of the Day
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 07:00 - 08:00, Four Seasons Ballroom F1+F2
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HOD03.01 - Treatment of Advanced Disease (ID 3411)
07:00 - 07:15 | Author(s): L. Paz-Ares
- Abstract
- Presentation
Abstract not provided
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MINI 05 - EGFR Mutant Lung Cancer 1 (ID 103)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:Y. Yatabe, R. Perez-Soler
- Coordinates: 9/07/2015, 16:45 - 18:15, Mile High Ballroom 2a-3b
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MINI05.08 - Comparison of the Efficacy of Dacomitinib v Erlotinib for NSCLC Pts with Del 19/L858R (ID 775)
17:25 - 17:30 | Author(s): L. Paz-Ares
- Abstract
- Presentation
Background:
To date there have been limited randomized comparisons of EGFR tyrosine kinase inhibitors (TKI) in EGFR mutant NSCLC. Dacomitinib is a potent, irreversible EGFR inhibitor that demonstrated robust activity in a phase 2 study for patients with common activating EGFR mutations. Additionally, preclinical data suggests greater activity in patients with common EGFR activating mutations in exon 19 or 21. ARCHER 1009 (NCT01360554) and A7471028 (NCT00769067) each compared the clinical activity of dacomitinib (D) versus erlotinib (E) in advanced NSCLC including patients with common activating EGFR mutations; pooled results are presented.
Methods:
Patients (pts) with locally advanced/metastatic NSCLC were randomized following progression with 1 or 2 prior chemotherapy regimens to treatment with dacomitinib (D) (45 mg PO QD) or erlotinib (E) (150 mg PO QD). The Phase 2 study (A7471028) was open label while the Phase 3 ARCHER 1009 study was double-blind and double dummy. Archived tumor tissue, ECOG performance status (PS) of 0-2, adequate organ function and informed consent were required. Results of the two studies were previously reported individually. Analyses were performed by pooling patients with common EGFR activating mutations from both studies to compare efficacy of D versus E.
Results:
121 patients with any EGFR mutation were enrolled into the two studies with 1 patient randomized but not treated; 101 (53 on D) pts had activating mutations in exon 19 or 21. For patients with exon19/21 mutations, the median PFS was 14.6 months (95%CI 9.0–18.2) for D and 9.6 months (95%CI 7.4–12.7) for E and unstratified HR 0.717 (95%CI 0.458–1.124) with 1-sided p=0.073. The median OS was 26.6 months (95%CI 21.6–41.5) for D and 23.2 months (95%CI 16.0–31.8) for E and unstratified HR 0.737 (95%CI 0.431–1.259) with 1-sided p=0.132. The corresponding pooled analyses were conducted separately in exon 19 and exon 21. The adverse-event profile did not differ between the activating mutation subset and the overall population. Figure 1
Conclusion:
Dacomitinib may be associated with an improved PFS and OS compared to Erlotinib in patients with exon 19/21 EGFR mutations. A prospective P3 study comparing D to another EGFR TKI in 1L EGFR mutated NSCLC is ongoing to verify these observations (NCT01774721).
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ORAL 02 - PD1 Axis Immunotherapy 2 (ID 87)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:E.B. Garon, H.J. Ross
- Coordinates: 9/07/2015, 10:45 - 12:15, Four Seasons Ballroom F1+F2
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ORAL02.01 - Phase 3, Randomized Trial (CheckMate 017) of Nivolumab (NIVO) vs Docetaxel in Advanced Squamous (SQ) Cell Non-Small Cell Lung Cancer (NSCLC) (ID 736)
10:45 - 10:56 | Author(s): L. Paz-Ares
- Abstract
- Presentation
Background:
Treatment options for patients with advanced SQ NSCLC who fail platinum-based doublet chemotherapy (PT-DC) are limited. NIVO, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor, demonstrates activity across NSCLC histologies and is approved in the US for treatment of metastatic SQ NSCLC with progression on or after platinum-based chemotherapy. We report results from a randomized, open-label, global phase 3 study (CheckMate 017; NCT01642004) comparing NIVO vs docetaxel in patients with previously treated SQ NSCLC and disease progression during/after one prior PT-DC regimen.
Methods:
Patients (N=272) were randomized 1:1 to receive either NIVO 3 mg/kg every 2 weeks (Q2W; n=135) or docetaxel 75 mg/m[2] Q3W (n=137) until disease progression or discontinuation due to toxicity or other reasons. For NIVO patients, treatment after initial progression was permitted at the investigator’s discretion, per protocol criteria. The primary objective was overall survival (OS). Secondary objectives included investigator-assessed objective response rate (ORR; per RECIST v1.1), progression-free survival (PFS), efficacy by PD-L1 expression (PD-L1 testing not required for enrollment), patient-reported outcomes (PRO), and safety. PRO analyses are presented in a separate abstract.
Results:
Treatment with NIVO led to 41% reduction in risk of death (hazard ratio [HR]=0.59; 95% CI: 0.44, 0.79; P=0.00025) and improved ORR (20% vs 9%; P=0.0083) and PFS (HR=0.62; 95% CI: 0.47, 0.81; P=0.0004) vs docetaxel (Table). Twenty-eight patients were treated with NIVO beyond initial progression, nine of whom demonstrated a non-conventional pattern of benefit (ie, reduction in target lesions with simultaneous appearance of new lesions, initial progression followed by tumor reduction, or no further progression for ≥2 tumor assessments). Across pre-specified cut-points (1%, 5%, and 10%), PD-L1 expression was neither prognostic nor predictive of benefit. OS HRs favored NIVO across most predefined patient subgroups. Grade 3–4 drug-related adverse events (AEs) were reported in 7% (9/131) of NIVO and 55% (71/129) of docetaxel patients. Grade 3–4 drug-related select AEs are shown below (Table). No deaths were related to NIVO vs 3 docetaxel-related deaths. Figure 1
Conclusion:
CheckMate 017 achieved its primary objective, demonstrating clinically superior and statistically significant OS with NIVO vs docetaxel in patients with advanced, previously treated SQ NSCLC. Benefit was seen regardless of PD-L1 status. The safety profile of NIVO 3 mg/kg Q2W is favorable vs docetaxel and consistent with prior studies. AEs were manageable with established guidelines. NIVO represents a new standard of care in this patient population. Updated OS and safety data will be presented.
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ORAL 32 - EGFR WT and MT Targeting (ID 144)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 2
- Moderators:K.J. O'Byrne, D.R. Gandara
- Coordinates: 9/09/2015, 16:45 - 18:15, Four Seasons Ballroom F3+F4
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ORAL32.03 - Efficacy and Safety of Necitumumab Continuation Therapy in Phase 3 SQUIRE Study (ID 1391)
17:07 - 17:18 | Author(s): L. Paz-Ares
- Abstract
- Presentation
Background:
The SQUIRE study demonstrated that the addition of necitumumab (N) to gemcitabine-cisplatin (GC) improved survival in patients with stage IV sq-NSCLC. This retrospective analysis compares efficacy and safety outcomes for patients who received single-agent N as continuation therapy after completion of chemotherapy treatment (CT) in GC+N arm to the continuation therapy-eligible population of the GC arm.
Methods:
Patients were randomized 1:1 to GC (G=1250 mg/m² iv, days 1 and 8; C=75 mg/m² iv, day 1) plus N (800 mg iv, days 1 and 8), or GC alone every 21 days up to 6 cycles. Patients in GC+N with no progression continued on N alone until progressive disease. In this analysis, we consider patients in GC+N arm who were alive and progression-free before the start of N single-agent therapy (GC+N arm continuation therapy patients) and patients in GC arm who were alive, progression-free after completion of CT and did not discontinue treatment due to adverse event (AE) (GC arm non-progressor patients). This analysis included patients in both arms who received ≥4 cycles of CT. Overall survival (OS) and progression-free survival (PFS) were measured from the date of randomization, with parameters estimated using the Kaplan-Meier method. Hazard ratios and 95% CIs between subgroups were estimated from stratified Cox proportional hazards models. OS and PFS for post-induction period were measured from the completion of CT + 21 days. Selected treatment-emergent AEs (TEAEs) for patients in each arm are presented in the table.
Results:
261 patients were progression-free, received ≥4 cycles of CT, and received ≥1 dose of N alone in GC+N arm. 215 pts in GC arm completed ≥4 cycles of CT, were progression-free, and did not discontinue due to AE. Patient baseline characteristics and exposure to CT were well balanced between GC+N and GC arms. Median OS from randomization in GC+N vs GC was 15.9 vs 15.0 months; HR 0.85 (95% CI, 0.69, 1.05). Median OS for post-induction period in GC+N vs GC was 11.5 vs 10.9 months; HR 0.84 (95% CI, 0.68; 1.04). Median PFS from randomization in GC+N vs GC was 7.4 vs 6.9 months; HR 0.86 (95% CI, 0.70, 1.06). Median PFS from post-induction period in GC+N vs GC was 3.2 vs 2.3 months; HR 0.85 (95% CI, 0.70, 1.04). Selected TEAEs (Overall):GC+N Continuation PatientsN = 261, % GC Non-ProgressorsN = 215, % Category Any Grade Grade ≥3 Any Grade Grade ≥3 Neutropenia 55.9 34.1 57.7 33.0 Anemia 46.7 10.0 49.3 8.8 Thrombocytopenia 26.1 9.6 29.3 12.6 Hypomagnesemia 42.1 14.9 18.6 0.9 Conjunctivitis 11.9 0.8 3.3 0 Rash 87.4 8.8 10.2 0.5 Arterial thromboembolic event 5.7 3.1 0.5 0 Venous thromboembolic event 9.2 3.8 4.2 0.9
Conclusion:
There was a consistent treatment effect in favor of GC+N continuation patients as compared to GC non-progressors with no unexpected increases in AEs.
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ORAL32.05 - EGFR IHC and FISH Correlative Analyses (SQUIRE Trial): Necitumumab + Gemcitabine-Cisplatin vs Gemcitabine-Cisplatin in 1st-Line Squamous NSCLC (ID 2651)
17:28 - 17:39 | Author(s): L. Paz-Ares
- Abstract
- Presentation
Background:
SQUIRE, a randomized phase III study, demonstrated that the addition of necitumumab (N) (a second-generation, recombinant, human immunoglobulin G1 EGFR antibody) to gemcitabine-cisplatin (GC) improved overall survival (OS) in patients with stage IV squamous non-small cell lung cancer (NSCLC). Analyses of the relationship between efficacy and epidermal growth factor receptor (EGFR) protein expression using the immunohistochemistry (IHC) H-score=200 cut-point were previously reported (Thatcher et al. Lancet Onc, 2015; doi: 10.1016/S1470-2045(15)00021-2). Here we report additional exploratory analyses of the relationship with EGFR protein, as well as analyses of EGFR gene copy number.
Methods:
SQUIRE included mandatory tissue collection from archived tumor. EGFR protein expression was assessed by IHC in a central lab, using the Dako EGFR PharmDx kit. Analyses of the relationships between efficacy outcomes with EGFR across the range of protein levels were performed, using methodologies including subpopulation treatment effect pattern plot (STEPP) with a sliding window target size of 200 patients. An exploratory assessment of EGFR gene copy number gain was performed in tissue sections using fluorescence in situ hybridization (FISH) (J Clin Pathol; 2009;62(11):970-7). Efficacy outcomes were estimated using the Kaplan-Meier method and hazard ratios estimated using an un-stratified Cox model. .
Results:
A total of 982 patients (89.8% of the ITT) had evaluable IHC assay results. The large majority of these patients (95.2%) had tumor samples expressing EGFR protein; only 4.8% had tumors without detectable EGFR protein (H-score=0). The STEPP analyses showed no consistent trend or obvious cut-point for the relationship between either OS or PFS with EGFR protein across the range of IHC values when comparing treatment arms. Archived tumor tissue with evaluable results for exploratory EGFR FISH analysis was available for 51.0% of patients (557 of 1093 ITT patients). Of these patients, 208 patients (37.3%) had increased EGFR gene copy number (FISH positive). A trend for greater necitumumab benefit was observed in EGFR FISH positive patients. Treatment HR (95% CI) for FISH positive and negative patients were 0.70 (0.52, 0.96) and 1.02 (0.80, 1.29) for OS, and 0.71 (0.52, 0.97) and 1.04 (0.82, 1.33) for PFS. However, the interaction of EGFR gene copy number gain with treatment was not statistically significant for either OS or PFS (p=0.066 and 0.057, respectively).
Conclusion:
The analysis of EGFR protein expression did not identify consistent trends related to efficacy outcomes across the range of IHC values. EGFR gene copy number gain showed a trend for a more favorable HR, but did not appear to be strongly predictive. However, both markers showed some evidence of potential trends that will be investigated further in future trials.
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P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 3
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.01-062 - Rash as a Marker for the Efficacy of Necitumumab in the SQUIRE Study (ID 97)
09:30 - 09:30 | Author(s): L. Paz-Ares
- Abstract
Background:
SQUIRE, a randomized, phase III study (n=1,093), demonstrated that the addition of the EGFR monoclonal antibody necitumumab (N) to gemcitabine-cisplatin (GC) improved overall survival in patients with stage IV squamous NSCLC. Rash is an established class side-effect associated with EGFR-targeting agents. Previous studies have suggested a positive association between rash and clinical outcomes with EGFR-targeted therapy.
Methods:
Pre-emptive treatment for rash was not allowed per protocol until completion of the first cycle of study therapy. For the purpose of this analysis, patients randomized to the N+GC arm were categorized and grouped according to whether or not they experienced rash during the first two cycles of study therapy. Patients who died or were lost to follow-up before completing two cycles of study therapy were not included in this analysis. Overall survival (OS) and progression-free survival (PFS) were measured from the date of randomization, with parameters estimated using the Kaplan-Meier method. Hazard ratios and 95% CIs between subgroups were estimated from stratified Cox proportional hazards models, with comparisons between arms using a stratified log-rank test.
Results:
505 patients were evaluable in the N+GC arm at the end of cycle 2 of which 69% experienced rash during cycle 1 and/or cycle 2. Patients experiencing rash in the N+GC arm had improved OS (HR=0.738, p=0.0001) and PFS (HR=0.808, p=0.0066) compared with patients in the GC arm. Patients experiencing rash in the N+GC arm had improved OS (HR=0.656, p=0.0001) compared with patients in the N+GC arm who did not experience rash. The difference in PFS between patients in the N+GC arm experiencing rash versus those not experiencing rash was not statistically significant. Median PFS and OS for patients experiencing rash in the N+GC arm was 6.2 mo and 13.6 mo respectively, as compared to 5.6 and 10.2 mo for patients in the N+GC arm without rash and 5.6 and 10.6 mo for patients in the GC arm.
*In comparison to the N+GC group with rashPatients alive and under follow-up after Cycle 2 N+GC with rash N=350 N+GC no rash N=155 GC N=508 Overall Survival, mo (CI) 13.6 mo (11.6, 15.2) 10.2 (8.7, 11.6) 10.6 (9.5, 11.9) HR* (95% CI) 0.656 (0.529, 0.813) 0.738 (0.631, 0.864) Stratified log-rank p value* 0.0001 0.0001 PFS, mo (CI) 6.2 mo (5.7, 6.9) 5.6 (5.0, 5.7) 5.6 (5.3, 5.6) HR* (95% CI) 0.867 (0.693, 1.084) 0.808 (0.692, 0.942) Stratified log-rank p value* 0.2127 0.0066
Conclusion:
Rash occurring during the first two cycles of treatment with necitumumab (N+GC) is associated with improved OS in patients with advanced squamous NSCLC.
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P1.01-064 - A Phase II Study of Gemcitabine-Cisplatin plus Necitumumab for Stage IV Sq-NSCLC (ID 927)
09:30 - 09:30 | Author(s): L. Paz-Ares
- Abstract
Background:
To report the efficacy and safety results from a study of necitumumab (N), manufactured under process D, modified from Process C, used in the pivotal SQUIRE study, in combination with gemcitabine (G) plus cisplatin (C) as first-line treatment in patients with advanced squamous non-small cell lung cancer (Sq-NSCLC). (NCT01788566)
Methods:
This was an open-label, single-arm, multicenter, phase II study in patients with advanced Sq-NSCLC. Patients were enrolled who were aged ≥18 years and had measurable, pathologically confirmed stage IV Sq-NSCLC without prior chemotherapy. Patients had ECOG-PS 0-1, adequate organ function, and life expectancy of ≥12 weeks. Patients received N (800 mg iv, Days 1 and 8) plus GC (G=1250 mg/m² iv, Days 1 and 8; C=75 mg/m² iv, Day 1) each 3-week cycle for up to 6 cycles. Patients with at least stable disease (SD) could continue to receive N alone until progressive disease (PD) or other discontinuation criteria. Primary endpoint was objective response rate (ORR) based on RECIST1.1. Secondary endpoints included overall survival (OS), progression-free survival (PFS), disease control rate (DCR), change in tumor size (CTS; % improvement in lesions), and safety.
Results:
Patients (N=61), median age 65 years, heavy metastatic disease burden; approximately 70% of the patients had metastases to ≥ 2 organ systems. Efficacy results, including an ORR of 48.1% are shown in the Table. Survival and PFS findings were similar to those reported in the SQUIRE study in the GC+N arm (SQUIRE results: median OS of 11.5 months, 1-year survival rate of 47.7%, and median PFS of 5.7 months). Median duration of treatment was 12 weeks (4 cycles) for G and C and 16 weeks (5 cycles) for N; the median relative dose intensity was 85% for G and 93% for C and N. Twenty-eight (46%) patients continued on single-agent N (median: 4 cycles). Skin reactions (n=49; 80.3%) and hypomagnesemia (n=21; 34.4%) were the most commonly reported adverse events of special interest (AESIs, all grades). AESI ≥ Grade 3 were skin reactions (n=8; 13.1%), thromboembolic events (n=7; 11.5%), hypomagnesemia (n=6; 9.8%), and hypersensitivity/ IRR (n=3; 4.9%). There were 27 deaths (20 due to PD and 7 due to AEs [5 had no causal relationship to study drug]) at the time of data cut-off.Table. Efficacy Results
N=61 ORR*† (CR+PR), n (%) [95% CI] 26/54 (48.1)† [34.34–62.16] CR 0 PR, n (%) 26/54 (48.1)† SD 18 (29.5) PD 9 (14.8) Not evaluable 1 (1.6) Not assessable 7 (11.5) DCR CR+PR+SD, n (%) [95% CI] 44 (81.5)† [68.57–90.75] Median OS, months (95% CI) 11.7 [7.59–NA] 1-year survival rate, % (95% CI) 47.6% [30.20–63.08] Median PFS, months (95% CI) 5.6 [3.68–6.87] Median CTS, (%) 42.1 *Assessed by investigators †Patients who had a post-baseline radiological assessment, n=54
Conclusion:
The efficacy results and the safety profile, with N manufactured under process D, are consistent with what is expected for this combination as first-line therapy of patients with metastatic Sq-NSCLC.
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P1.01-080 - Treatment Rationale and Study Design for the Phase 3 JUNIPER Study: Abemaciclib vs Erlotinib in Patients with Stage IV NSCLC and KRAS Mutation (ID 1438)
09:30 - 09:30 | Author(s): L. Paz-Ares
- Abstract
Background:
Abemaciclib (LY2835219) is a potent, selective small molecule inhibitor of CDK4/6, which has been shown to inhibit cell cycle progression by preventing the phosphorylation and functional inactivation of the Rb tumor-suppressor protein. Cell cycle dysfunction due to abnormalities in the CDK4/6 pathway occurs in NSCLC. KRAS mutant xenografts predict for greater sensitivity to CDK4/6 inhibitors. In a phase 1 study with abemaciclib (Goldman ASCO 2014), 16 patients with KRAS mutant tumors (N=29) had a response of stable disease (SD) or better (disease control rate [DCR]=55.2%), and 9 patients with KRAS wild-type tumors (N=24) had a response of SD or better (DCR=37.5%).
Methods:
JUNIPER (NCT02152631) is a randomized, phase 3 study of abemaciclib (200 mg orally q12hrs) + best supportive care (BSC) versus erlotinib (150 mg orally q24hrs) + BSC in patients with stage IV NSCLC whose tumors have detectable KRAS mutations and who have progressed after platinum-based chemotherapy and one other prior therapy or who are not eligible for further chemotherapy. About 550 patients will be randomized to abemaciclib or erlotinib 3:2 ratio using following factors: number of prior chemotherapy regimens (1 vs. 2), ECOG PS (0 vs. 1), gender (male vs. female) and KRAS mutation (G12C vs. others). This design has 80% power to detect overall survival (OS) hazard ratio (HR) of 0.75 (type I error 0.045) and progression-free survival (PFS) HR of 0.67 (type I error 0.005). Erlotinib was chosen as the control arm, as it is the only agent indicated for both 2nd and 3rd line therapy in advanced NSCLC. Treatment will continue until disease progression or unacceptable toxicity occurs, with assessments every 28 days, followed by short-term and long-term follow-up. Primary objectives are to compare OS and PFS of the treatment arms. Enrollment began December 2014. If the primary objectives are achieved, this study will provide results on an alternative treatment option, abemaciclib + BSC, for patients with NSCLC whose tumors have detectable KRAS mutations, currently a patient population with few treatment options.
Results:
Not applicable
Conclusion:
Not applicable
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P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.01-085 - Abemaciclib in Combination with Single Agent Options in Stage IV NSCLC, a Phase 1b Study (ID 125)
09:30 - 09:30 | Author(s): L. Paz-Ares
- Abstract
Background:
Abemaciclib, a cell cycle inhibitor selective for CDK4/6, demonstrated acceptable safety and early clinical activity in metastatic NSCLC, given orally as monotherapy on a continuous schedule. Combinations of abemaciclib showed greater activity compared with monotherapy in KRAS-mutant NSCLC preclinical models. Primary aim of study NCT02079636 was safety/tolerability of combination therapy with abemaciclib; secondary aims included pharmacokinetics and antitumor activity.
Methods:
In this open-label 3+3 dose-escalation study with expansion cohorts, eligibility included stage IV NSCLC, measurable or nonmeasurable disease (RECISTv1.1), ECOG PS ≤1, and 1-3 prior therapies. Abemaciclib was combined with pemetrexed (Part A, nonsquamous, 500 mg/m[2] IV day 1), gemcitabine (Part B, 1250 mg/m[2] IV days 1 and 8), ramucirumab (Part C, 10 mg/kg IV day 1, or 8 or 10 mg/kg IV days 1 and 8) (Q21), or LY3023414 (dual PI3K-mTOR inhibitor) (Part D, 100 mg, 150 mg or 200 mg orally Q12H). In escalation, patients were dosed continuously until progression with abemaciclib at 100 mg (Part D), 150 mg or 200 mg orally Q12H.
Results:
As of February 27, 2015, 70 patients (Parts A-C) received ≥1 dose; 15 patients at 150 mg and 55 patients (including all 39 patients in expansion) at 200 mg Q12H abemaciclib. The MTD was established at 200 mg Q12H abemaciclib for Parts A-C. See Table 1 for treatment-emergent adverse events (TEAEs). Stable disease was observed in 13/23 patients in Part A; 7 unknown, 4/24 patients in Part B; 10 unknown, and 7/23 patients in Part C; 12 unknown. In Parts A-C, 18/70 (26%) patients started ≥4 cycles (Part A=9, Part B=3, Part C=6). Three confirmed PRs were observed: Part B, 1 patient with squamous histology (unknown mutation status), Part C, 1 patient with nonsquamous histology (KRAS mutation positive; EGFR mutation negative), and 1 patient with squamous histology (unknown mutation status). Updated analyses will be presented including Part D and longer term follow-up for Parts A-C through approximately June 2015. Table 1. TEAEs related to treatment (≥20% in ≥1 part)% All grades (% Gr3/4) Part A (n=23) Part B (n=24) Part C (n=23) Diarrhea 65 (4) 50 (17) 52 (9) Fatigue 57 (9) 63 (8) 17 (4) Nausea 35 (0) 50 (4) 48 (9) Neutropenia 61 (61) 50 (33) 17 (4) Anemia 57 (26) 33 (17) 9 (0) Thrombocytopenia 39 (9) 38 (8) 17 (13) Decreased appetite 30 (0) 25 (0) 22 (0) Vomiting 9 (0) 21 (0) 35 (0) Blood creatinine increased 30 (0) 8 (0) 17 (4) Leukopenia 30 (22) 17 (8) 9 (4)
Conclusion:
Abemaciclib combined with single-agents with acceptable toxicity. Safety findings observed in Parts A and B are consistent with AEs expected when combining myelosuppressive compounds with abemaciclib, resulting in an increased myelosuppressive effect. In Part C, safety findings are consistent with those of single-agents. Tumor responses were observed in Parts B and C.
