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G. Blumenschein, Jr.
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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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ORAL02.02 - Safety and Efficacy of Nivolumab in an Ongoing Trial of a PD-L1+/- Patient Population with Metastatic Non-Small Cell Lung Cancer (ID 851)
10:45 - 12:15 | Author(s): G. Blumenschein, Jr.
- Abstract
- Presentation
Background:
Nivolumab (NIVO), a fully human IgG4 programmed death-1 (PD-1), immune checkpoint inhibitor antibody, has demonstrated durable responses and tolerability in heavily pretreated patients with advanced non-small cell lung cancer (NSCLC). NIVO was recently approved for the treatment of patients with metastatic squamous (SQ) NSCLC with progression on or after platinum-based chemotherapy. Conducted mostly in community-based oncology centers, this ongoing trial explores the safety of NIVO in patients with previously-treated PD-L1[+/-] metastatic SQ or non-squamous (NSQ) NSCLC.
Methods:
Eligible patients are enrolled in 4 subgroups: 1) SQ, performance status (PS) 0–1, ≥2 prior therapies; 2) SQ, PS 0–1, 1 prior therapy; 3) NSQ, PS 0–1, ≥1 prior therapy; and 4) SQ or NSQ, PS 2, ≥1 prior therapy. Patients with both PD-L1[+] and PD-L1[-] tumors are eligible. Patients receive NIVO 3 mg/kg IV (60 minutes) Q2W either until progressive disease (PD)/unacceptable toxicity (Cohort A) or for 1 year with the possibility of retreatment upon disease progression (Cohort B). Primary objective is to estimate incidence of high-grade (CTCAE v4.0 Grade 3–4 and 5), select treatment-related adverse events (STRAEs); exploratory efficacy assessments include ORR, PFS, and OS.
Results:
From 4/16/14 to 12/31/14, 824 patients were treated and have demographic and safety data available; 483 patients remained on study as of 12/31/2014. 395 patients had evaluable radiographic tumor assessments at first assessment (Week 9). Demographics, safety, and tumor response by PD-L1 status are reported. Figure 1
Conclusion:
Safety and tolerability are consistent with prior NIVO experience and no new safety signals have been identified in this trial of SQ/NSQ NSCLC patients. Immune-related toxicities are manageable in a community practice setting using previously-developed safety algorithms. The frequency of STRAEs of interest was similar between patients with PS 0–1 and those with PS 2. Early data from this large, multicenter trial suggests that patients with pretreated advanced NSCLC benefit from NIVO therapy regardless of tumor PD-L1 status, histology type, and PS status.
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ORAL 11 - Clinical Trials 1 (ID 100)
- Event: WCLC 2015
- Type: Oral Session
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:A.K. Nowak, F. Detterbeck
- Coordinates: 9/07/2015, 10:45 - 12:15, 702+704+706
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ORAL11.02 - Phase I Study of Anti-Mesothelin Antibody Drug Conjugate Anetumab Ravtansine (ID 1574)
10:45 - 12:15 | Author(s): G. Blumenschein, Jr.
- Abstract
- Presentation
Background:
Anetumab ravtansine (BAY 94-9343) is a novel fully humanized anti-mesothelin IgG1 antibody conjugated to a ravtansine, a maytansine derivative DM4 antitubulin cytotoxic agent. We report results from a phase I study evaluating the safety, PK and tumor response in patients (pts) with advanced solid tumors treated with anetumab, with a particular focus on patients with mesothelioma.
Methods:
Anetumab was given IV every 21 days (q3w) in 77 pts: 45 pts in 10 dose escalation cohorts from 0.15 to 7.5 mg/kg (21 mesothelioma, 9 pancreatic, 5 breast, 4 ovarian, 6 other), and 32 pts in 2 expansion cohorts (12 mesothelioma and 20 ovarian); 38 pts were treated at MTD in escalation and expansion cohorts (16 mesothelioma, 21 ovarian, 1 breast). Clinical and laboratory safety assessments were made on D1, D8 and D15 in C1-C3 and on D1 in subsequent cycles. Tumor assessments were made q6wks up to C8 and q12wks thereafter. Mesothelin expression in archival tumor samples was assessed retrospecively by IHC (SP74, Ventana).
Results:
Thirty-two males and 45 females were treated [mean age 62 yrs (range, 18-84 yrs), body weight 77 kg (44-113 kg), ECOG ≤1, median prior cytotoxic regimens: overall 4 (1-9), mesothelioma 1 (1-4)]. Non-tolerated anetumab dose was 7.5 mg/kg (DLTs: 1 pt with G2 keratitis and G3 neuropathy, 1 pt with G4 keratitis and G2 neuropathy). Anetumab MTD was 6.5 mg/kg (DLT: G3 AST increase). Only one DLT occurred at doses below MTD (G3 hyponatremia, 5.5 mg/kg). No drug-related deaths and few drug-related SAEs (7 total and 5 at MTD) were reported. Seventeen of 38 (45%) pts total or 7 of 16 (44%) mesothelioma pts at MTD had drug-related AE requiring dose reduction (G1-4 keratitis, G2-3 neuropathy, G3 fatigue, anorexia, asthenia, diarrhea, N&V, AST increase). LFT increases were the most common drug-related laboratory abnormality at MTD: AST in 7 pts (2 G3), ALT in 6 pts (no G3), alkaline phosphatase in 4 pts (one G3) and bilirubin increase in 1 pt (no G3). There were no drug-related G3 hematological abnormalities at any dose. Fourteen of 38 (37%) pts total or 4 of 16 (25%) mesothelioma pts at MTD had G1-4 keratitis (worst G3-4 in 3 pts, blurred vision in 10, dose reduction in 8, dose delay in 11, all fully reversible). Anetumab at the MTD showed a PR in 6 pts (19%) and SD in 18 pts (47%) overall. Five of 16 (31%) mesothelioma pts at the MTD had durable PR (>600 days in 4 pts) and 7 (44%) had SD. Five PRs occurred in 11 mesothelioma pts who received anetumab as second line treatment (45% response rate).
Conclusion:
Anetumab at the MTD (6.5 mg/kg) showed encouraging efficacy with durable PR in pts with advanced mesothelioma. At the MTD, all drug-related AEs were reversible and non-life-threatening but required dose reduction in about half of pts, most commonly due to G1-4 keratitis and G2-3 peripheral neuropathy. Given this benefit-risk ratio, the recommended phase II dose of anetumab in second line treatment of advanced mesothelioma is 6.5 mg/kg IV q3w.
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P3.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 208)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.01-065 - PET Tumor Response by PERCIST Predicts Local-Regional Control in Locally Advanced NSCLC after Concurrent Chemoradiotherapy with Erlotinib (ID 1242)
09:30 - 17:00 | Author(s): G. Blumenschein, Jr.
- Abstract
Background:
Assessing response of locally advanced non-small cell lung cancer (NSCLC) after concurrent chemoradiotherapy by computed tomography (CT) can be complicated by treatment-related pneumonitis or fibrosis. Hypothesizing that measurements of tumor response by [18]F-fluorodeoxyglucose standardized uptake values (SUVs) on positron emission tomography (PET) are more reliably associated with treatment outcomes than those by CT, we compared outcomes and responses according to PET SUV vs. CT among patients in a phase II study of erlotinib+chemoradiation for stage III NSCLC.
Methods:
Trial 2005-1023 enrolled 46 patients in 2007–2010; patients received 63 Gy in 35 fractions over 7 weeks with daily erlotinib and weekly paclitaxel-carboplatin. Tumor response was assessed on diagnostic CT scans with contrast or CT from PET-CT and scored according to RECIST 1.1. Tumor response was also assessed by PERCIST 1.0 (based on SUV) as follows: complete response (CR), disappearance of all measurable tumors; partial response (PR), ≥30% reduction in the sum of SUVs of target lesions; progressive disease (PD), ≥30% increase in the sum of SUVs of target lesions; and stable disease (SD), insufficient change in SUV to qualify for PR or PD. The longest diameter of measurable primary lesions and the short axis of measurable lymph nodes were measured. All non-target lesions were also measured. Two-sided Pearson’s chi-square tests were used to assess frequency associations. Overall survival (OS) and local-regional control (LRC) rates were assessed from treatment start by Kaplan-Meier analysis and log-rank tests; P≤0.05 indicated significance.
Results:
One patient did not have CT and PET after treatment. For the 45 evaluable patients, best response by PET-CT at 6 months after treatment was CR for 15 patients (33%), PR for 19 (42%), SD for 0, PD for 4 (9%), and not available due to did not have baseline or post treatment PET for 7 (16%). Best response by CT at 6 months was CR for 11 (24%), PR for 27 (60), SD for 3 (7%), and PD for 4 (9%) (P<0.001). The 3 patients with SD by CT all died within 7 months after treatment; the 4 patients with PD had new distant metastases. Four-year OS was associated with best overall response on both PET and CT at 6 months (P<0.05) and at 1 year (P<0.05). LRC was associated with best overall response on PET (P<0.01) and best primary tumor response on PET (P<0.05) at 6 and 12 months. Lymph node response was not associated with OS or LRC by PET or CT.
Conclusion:
The CR rate was higher with PET than with CT. Tumor response at 6 months by PET or CT predicted treatment outcomes after chemoradiotherapy for stage III NSCLC. The best overall and primary tumor response by PET within 6 months after treatment was more reliably associated with LRC than was response on CT because of difficulty to assess response due to pneumonitis/lung fibrosis.
