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Luana Calabro
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MA 19 - Mesothelioma: Bench to Bedside (ID 680)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Mesothelioma
- Presentations: 1
- Moderators:Dean A Fennell, Hedy Lee Kindler
- Coordinates: 10/18/2017, 11:00 - 12:30, Room 315
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MA 19.02 - Tremelimumab plus Durvalumab in First- or Second-Line Mesothelioma Patients: Final Analysis of the NIBIT-MESO-1 Study (ID 9202)
11:00 - 12:30 | Presenting Author(s): Luana Calabro
- Abstract
- Presentation
Background:
The anti-CTLA-4 tremelimumab as monotherapy showed initial signs of activity in second-line malignant mesothelioma (MM) patients (Calabrò et al., Lancet Oncol, 2013; Calabrò et al., Lancet Respir Med, 2015), though it failed to improve the overall survival (OS) of second or third line mesothelioma patients compared to placebo in the DETERMINE study (Maio et al., Lancet Oncol, in press). These results and the efficacy of targeting the PD-1/PD-L1 axis in a variety of tumor types, prompted the NIBIT-MESO-1 study aimed at investigating the activity and safety of tremelimumab combined with the anti-PD-L1 durvalumab in MM patients. Here, we report conclusive efficacy and safety analysis from the fully-enrolled NIBIT-MESO-1 study.
Method:
The NIBIT-MESO-1 is a phase II, open-label, single Center study. Forty MM patients received tremelimumab at 1 mg/Kg i.v. every 4 weeks (Q4W) for 4 doses, and durvalumab at 20 mg/Kg i.v. Q4W for 13 doses. Primary objective is immune-related (ir)-objective response rate; secondary are ir-disease control rate, ir-progression free survival, OS, and safety. Tumor assessment per ir-modified RECIST or ir-RECIST 1.1 for pleural or peritoneal MM, respectively, was performed at baseline and q12 weeks. Adverse events (AEs) were recorded according to CTC v4.0.
Result:
From October 2015 to October 2016, 40 MM patients (38 pleural and 2 peritoneal), median age 64 years (range 41-80), ECOG performance status 0 (n = 19) or 1 (n = 21) were enrolled in the study. MM histology was epithelioid (n = 32), biphasic (n = 5), sarcomatoid (n = 2) or undefined (n = 1). As of April 2017, 12 first or 28 second-line MM patients received a median of 6 doses of therapy (range = 1-13). Ten ir-objective responses (9 confirmed) were observed (25%), and 25 patients reached an ir-disease control rate (62.5%). The median OS was not reached with a median follow-up of 9.5 months (inter-quartile range: 6.2-12.5 months). Thirty patients (75%) experienced any grade irAEs: grade 1-2 irAEs were observed in 67.5% and grade 3-4 irAEs in 17.5%. AEs were generally manageable and reversible per protocol guidelines.
Conclusion:
These data suggest that the combination of tremelimumab and durvalumab is active, with a good safety profile in MM patients, and warrant further exploration. Clinical trial information: .
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OA 02 - Mesothelioma: Challenges For New Treatment (ID 653)
- Event: WCLC 2017
- Type: Oral
- Track: Mesothelioma
- Presentations: 1
- Moderators:S. Hasegawa, Anna Nowak
- Coordinates: 10/16/2017, 11:00 - 12:30, F205 + F206 (Annex Hall)
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OA 02.01 - Randomized Phase II Study of Anetumab Ravtansine or Vinorelbine in Patients with Malignant Pleural Mesothelioma (ID 9377)
11:00 - 12:30 | Author(s): Luana Calabro
- Abstract
- Presentation
Background:
Anetumab ravtansine (BAY 94-9343) is a novel fully human anti-mesothelin IgG1 antibody conjugated to the maytansinoid tubulin inhibitor DM4. We report the results of a randomized phase II trial of anetumab ravtansine compared to vinorelbine in patients with advanced malignant pleural mesothelioma (MPM) who have high mesothelin expression and have progressed on platinum/pemetrexed-based first-line chemotherapy (NCT02610140).
Method:
Patients (≥18 years) with locally advanced or metastatic MPM with progressive disease following first-line treatment with pemetrexed-based chemotherapy, with or without bevacizumab, were eligible. Patients were pre-screened based on obligatory tumor staining for mesothelin as determined by the Ventana MSLN (SP74) immunohistochemistry assay. The primary efficacy endpoint was progression-free survival (PFS) per central radiologic review using modified RECIST criteria for MPM. Secondary objectives included overall survival, tumor response, and safety. Patients were randomized in a 2:1 ratio to anetumab ravtansine 6.5 mg/kg Q3W IV or vinorelbine 30 mg/m[2] QW IV.
Result:
A total of 166 patients were randomized to anetumab ravtansine and 82 to vinorelbine; 3 and 10 patients, respectively, not receiving treatment were included for efficacy but not safety assessments. The treatment arms were evenly balanced, with 73% male, 64% ECOG performance status 1, 96% epithelioid histology, and a mean 2.5 (±2.4) months since last progression. The median duration of treatment (anetumab vs vinorelbine) was 12.6 weeks (range 3-61) vs 13.0 weeks (range 1-43). Treatment-emergent grade (G) ≥3 adverse events (AEs) were seen in 85 (52.1%) and 53 (73.6%) of patients, respectively. G3/G4 neutropenia (22.2%/16.7%) occurred in the vinorelbine arm whereas corneal epitheliopathy (39.3% all grade, 1.8% G3) was distinct for the anetumab ravtansine arm. Serious AEs (any grade) were similar; 52 (31.9%) vs 25 (34.7%). Treatment-emergent AEs leading to dose modification were 42.9% in the anetumab ravtansine arm and 80.6% in the vinorelbine arm. There was one treatment-related G5 event in each arm. Median PFS was 4.3 months (95% CI:4.1, 5.2) for anetumab ravtansine vs 4.5 months (4.1, 5.8) for vinorelbine; hazard ratio 1.22 (0.85, 1.74), p=0.859. Fourteen (8.4%) patients in the anetumab ravtansine arm had an objective response vs 5 (6.1%) in the vinorelbine arm, with no complete responses. Interim median overall survival was 10.1 mo (7.6, -) vs 11.6 mo (7.7, 12.5), respectively, p-value 0.721.
Conclusion:
In relapsed MPM, anetumab ravtansine was not superior to vinorelbine with respect to PFS.
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