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e-Poster Display Session

68P - Evaluation of flat dosing for nivolumab (NIVO) + ipilimumab (IPI) in first-line (1L) unresectable malignant pleural mesothelioma (MPM): CheckMate 743 (CM 743)

Date

09 Dec 2020

Session

e-Poster Display Session

Topics

Immunotherapy

Tumour Site

Mesothelioma

Presenters

Anne Tsao

Citation

Annals of Oncology (2020) 31 (suppl_7): S1441-S1451. 10.1016/annonc/annonc392

Authors

A. Tsao1, P. Baas2, A. Nowak3, G. Zalcman4, N. Fujimoto5

Author affiliations

  • 1 MD Anderson Cancer Center, Houston/US
  • 2 The Netherlands Cancer Institute and Leiden University Medical Center, Amsterdam/NL
  • 3 Medical School, University of Western Australia and Department of Medical Oncology, Sir Charles Gairdner Hospital, Perth/AU
  • 4 Hôpital Bichat-Claude Bernard, Assistance Publique Hôpitaux de Paris, Université de Paris, Paris/FR
  • 5 Okayama Rosai Hospital, Okayama/JP
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Abstract 68P

Background

Weight-based dosing with NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W in CM LBA1 (NCT02899299) has been shown to be efficacious and safe in patients (pts) with untreated unresectable MPM. This analysis evaluates the benefits/risks of 1L NIVO 360 mg Q3W + IPI 1 mg/kg Q6W for pts with unresectable MPM.

Methods

Pharmacometric analyses included population pharmacokinetics predictions and exposure–response (efficacy and safety) assessments. Similar methodology was previously applied to support the approval for flat-dose NIVO monotherapy. Mean exposures were predicted with NIVO 3 mg/kg Q2W, 240 mg Q2W, or 360 mg Q3W when administered with IPI 1 mg/kg Q6W. The relationships between predicted NIVO exposure and overall survival (OS) or grade ≥ 2 immune-mediated adverse events (Gr 2+ IMAEs) were evaluated using the multivariate Cox proportional hazard (CPH) model. Clinical subgroup efficacy and safety based on baseline body weight (BW; < 60 kg, ≥ 60 < 70 kg, ≥ 70 < 80 kg, and ≥ 80 kg) were also assessed using data from CM LBA1.

Results

The predicted exposure of the flat dose resulted in similar Cminss (other exposures higher) relative to weight-based dosing. However, the predicted peak concentration after first dose of NIVO 360 mg Q3W was ∼82% below the median steady-state peak concentration with NIVO 10 mg/kg Q2W, a dosing regimen previously demonstrated to be well-tolerated. CPH analysis suggested that BW was not a significant covariate on OS or Gr 2+ IMAEs. Model-predicted mean probabilities for OS and Gr 2+ IMAEs were comparable between NIVO 360 mg Q3W and 3 mg/kg Q2W. Clinical CM LBA1 data demonstrated that OS benefit of NIVO vs chemo and key safety endpoints were not compromised across BW subgroups (table). Table: 68P

OS and safety

< 60 kg ≥ 60 < 70 kg ≥ 70 < 80 kg ≥ 80 kg
OS (NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W; Chemo)
Patients, n Median OS, mo HR (95% CI) 56; 56 15.8; 13.5 0.80 (0.52, 1.24) 76; 86 16.2; 13.7 1.00 (0.70, 1.42) 78; 63 19.6; 15.1 0.65 (0.44, 0.98) 90; 79 22.8; 15.2 0.60 (0.41, 0.88)
Safety (NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W)
Gr 3–4 AEs,a n (%) 27 (48) 40 (53) 40 (51) 52 (58)
All SAEs,a n (%) 33 (59) 37 (49) 44 (56) 50 (56)
Gr 2+ IMAEs ≥10%,a n (%)
Diarrhea/colitis 6 (11) 5 (7) 7 (9) 5 (6)
Hepatitis 2 (4) 2 (3) 4 (5) 9 (10)
Rash 3 (5) 9 (12) 5 (6) 8 (9)
Hypothyroidism/thyroiditis 2 (4) 1 (1) 2 (3) 12 (13)

aInclude events reported between first dose and 30 days (Gr 3-4 AEs and SAEs) or 100 days (Gr 2+ IMAEs) after last dose of study therapy.

Conclusions

These results suggest that the benefit/risk of 360 mg Q3W NIVO + IPI is comparable with NIVO 3 mg/kg Q2W + IPI, supporting an alternative dosing regimen in pts with untreated unresectable MPM.

Clinical trial identification

NCT02899299; Release date: 25 May 2016.

Editorial acknowledgement

Writing and editorial assistance were provided by Janaki Iyer, PhD, of Caudex, funded by Bristol Myers Squibb.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb.

Disclosure

A.S. Tsao: Advisory/Consultancy: Bristol Myers Squibb, Eli Lilly, Genentech, Roche, Novartis, Ariad, EMD Serono, Merck, Seattle Genetics, Astra-Zeneca, Boehringer-Ingelheim, Sellas Life Science, Takeda, Epizyme, Huron; Research grant/Funding (self): Eli Lilly, Millennium, Polaris, Genentech, Merck, Boehringer Ingelheim, Bristol Myers Squibb, Ariad, Epizyme, Seattle Genetics, Takeda, EMD Serono; Licensing/Royalties: UptoDate, Wiley. P. Baas: Advisory/Consultancy: MSD, AstraZeneca, Takeda, Bristol Myers Squibb; Research grant/Funding (self): Bristol Myers Squibb. A. Nowak: Honoraria (self): Bristol Myers Squibb; Advisory/Consultancy: Bayer Pharmaceuticals, Pharmabcine, Trizell, Roche Pharmaceuticals, Boehringer Ingelheim, Merck Sharp Dohme, Douglas Pharmaceuticals, Atara Biotherapeutics; Research grant/Funding (self): AstraZeneca, Douglas Pharmaceuticals; Travel/Accommodation/Expenses: Boehringer Ingelheim, AstraZeneca . G. Zalcman: Honoraria (self): AstraZeneca, Bristol Myers Squibb; Honoraria (institution): AstraZeneca, Bristol Myers Squibb, Roche; Advisory/Consultancy: Bristol Myers Squibb, AstraZeneca, MSD, Da Volterra, Inventiva; Research grant/Funding (self): Roche; Research grant/Funding (institution): Roche, Inventiva; Travel/Accommodation/Expenses: AstraZeneca, Bristol Myers Squibb, Roche, Boehringer Ingelheim, Pfizer, AbbVie. N. Fujimoto: Honoraria (self): ONO Pharmaceutical, Bristol Myers Squib, Daiichi Sankyo; Advisory/Consultancy: ONO Pharmaceutical; Research grant/Funding (institution): ONO Pharmaceutical. S. Peters: Honoraria (self): AbbVie, Amgen, AstraZeneca, Bayer, Biocartis, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffman- La Roche, Foundation Medicine, Illumina, Janssen, Merck Sharp and Dohme, Merck Serono, Merrimack, Novarti; Advisory/Consultancy: AbbVie, Amgen, AstraZeneca, Bayer, Biocartis, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffman- La Roche, Foundation Medicine, Illumina, Janssen, Merck Sharp and Dohme, Merck Serono, Merrimack, Novarti; Speaker Bureau/Expert testimony: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffman-La Roche, Merck Sharp and Dohme, Novartis, Pfizer, Sanofi, Takeda; Research grant/Funding (self): Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, F. Hoffman-La Roche, Illumina, Merck Sharp and Dohme, Merck Serono, Novartis, Pfizer. C. Baudelet: Full/Part-time employment: Bristol Myers Squibb; Shareholder/Stockholder/Stock options: Bristol Myers Squibb. P. Aanur: Full/Part-time employment: Bristol Myers Squibb. M. Osawa: Full/Part-time employment: Bristol Myers Squibb K.K.; Shareholder/Stockholder/Stock options: Bristol Myers Squibb K.K.. A. Tendolkar: Full/Part-time employment: Bristol Myers Squibb; Shareholder/Stockholder/Stock options: Bristol Myers Squibb. Y.(. Feng: Shareholder/Stockholder/Stock options: Bristol Myers Squibb; Full/Part-time employment: Bristol Myers Squibb. J. Sheng: Shareholder/Stockholder/Stock options: Bristol Myers Squibb; Full/Part-time employment: Bristol Myers Squibb.

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