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Veliparib and nivolumab in combination with platinum doublet chemotherapy in patients with metastatic or advanced non-small cell lung cancer: A phase 1 dose escalation study.

Publication ,  Journal Article
Clarke, JM; Patel, JD; Robert, F; Kio, EA; Thara, E; Ross Camidge, D; Dunbar, M; Nuthalapati, S; Dinh, MH; Bach, BA
Published in: Lung Cancer
November 2021

OBJECTIVES: Both combinations of the PARP inhibitor veliparib plus platinum doublet chemotherapy (CT), and the programmed death receptor-1 (PD-1) inhibitor nivolumab plus CT have demonstrated encouraging efficacy for treatment of non-small cell lung cancer (NSCLC). This phase 1 dose-escalation study (NCT02944396) evaluated the quadruple combination of veliparib with nivolumab and doublet CT in patients with unresectable advanced/metastatic NSCLC. MATERIALS AND METHODS: Patients were enrolled into five dosing cohorts: patients received veliparib 120 mg twice daily (BID) combined with nivolumab 360 mg, carboplatin AUC 6 mg/mL∙min, and paclitaxel 200 mg/m2 (C/PAC) or veliparib 80/120/200/240 mg BID in combination with nivolumab 360 mg, carboplatin AUC 6 mg/mL∙min, and pemetrexed 500 mg/m2 (C/PEM). Primary objective was to identify the recommended phase 2 dose (RP2D) of veliparib + nivolumab + CT. Safety, tolerability, and efficacy of this combination were also assessed. RESULTS: Twenty-five patients were enrolled: 6 patients received veliparib 120 mg BID + nivolumab + C/PAC and 19 received veliparib (80-240 mg BID) + nivolumab + C/PEM. No dose-limiting toxicities were reported, and the RP2Ds were veliparib 120 mg BID + nivolumab + C/PAC, and veliparib 240 mg BID + nivolumab + C/PEM. The most common any-grade adverse events (AEs) were fatigue (56%), nausea (52%), and anemia (48%). Grade 3/4 AEs included anemia (32%) and neutropenia (24%), and the most frequent serious AE was malignant neoplasm progression (12%). Veliparib exhibited approximately dose proportional kinetics in the dose range 80-240 mg BID combined with nivolumab and C/PEM, with no effects on pemetrexed pharmacokinetics. Overall, the confirmed objective response rate was 40%, and best overall response was 64%. CONCLUSION: Veliparib combined with nivolumab and platinum doublet CT was tolerated in patients with advanced/metastatic NSCLC, and no evidence of drug-drug interaction was observed. Although preliminary, this quadruple therapy may have promising antitumor activity.

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Published In

Lung Cancer

DOI

EISSN

1872-8332

Publication Date

November 2021

Volume

161

Start / End Page

180 / 188

Location

Ireland

Related Subject Headings

  • Platinum
  • Oncology & Carcinogenesis
  • Nivolumab
  • Lung Neoplasms
  • Humans
  • Carcinoma, Non-Small-Cell Lung
  • Benzimidazoles
  • Antineoplastic Combined Chemotherapy Protocols
  • 3211 Oncology and carcinogenesis
  • 3202 Clinical sciences
 

Citation

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Clarke, J. M., Patel, J. D., Robert, F., Kio, E. A., Thara, E., Ross Camidge, D., … Bach, B. A. (2021). Veliparib and nivolumab in combination with platinum doublet chemotherapy in patients with metastatic or advanced non-small cell lung cancer: A phase 1 dose escalation study. Lung Cancer, 161, 180–188. https://doi.org/10.1016/j.lungcan.2021.09.004
Clarke, Jeffrey M., Jyoti D. Patel, Francisco Robert, Ebenezer A. Kio, Eddie Thara, D. Ross Camidge, Martin Dunbar, Silpa Nuthalapati, Minh H. Dinh, and Bruce A. Bach. “Veliparib and nivolumab in combination with platinum doublet chemotherapy in patients with metastatic or advanced non-small cell lung cancer: A phase 1 dose escalation study.Lung Cancer 161 (November 2021): 180–88. https://doi.org/10.1016/j.lungcan.2021.09.004.
Clarke, Jeffrey M., et al. “Veliparib and nivolumab in combination with platinum doublet chemotherapy in patients with metastatic or advanced non-small cell lung cancer: A phase 1 dose escalation study.Lung Cancer, vol. 161, Nov. 2021, pp. 180–88. Pubmed, doi:10.1016/j.lungcan.2021.09.004.
Clarke JM, Patel JD, Robert F, Kio EA, Thara E, Ross Camidge D, Dunbar M, Nuthalapati S, Dinh MH, Bach BA. Veliparib and nivolumab in combination with platinum doublet chemotherapy in patients with metastatic or advanced non-small cell lung cancer: A phase 1 dose escalation study. Lung Cancer. 2021 Nov;161:180–188.
Journal cover image

Published In

Lung Cancer

DOI

EISSN

1872-8332

Publication Date

November 2021

Volume

161

Start / End Page

180 / 188

Location

Ireland

Related Subject Headings

  • Platinum
  • Oncology & Carcinogenesis
  • Nivolumab
  • Lung Neoplasms
  • Humans
  • Carcinoma, Non-Small-Cell Lung
  • Benzimidazoles
  • Antineoplastic Combined Chemotherapy Protocols
  • 3211 Oncology and carcinogenesis
  • 3202 Clinical sciences