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COAST: An Open-Label, Randomized, Phase 2 Platform Study of Durvalumab Alone or in Combination with Novel Agents in Patients with Locally Advanced, Unresectable, Stage III NSCLC

Conference Correspondent  - Dual IO 2021 Year in Review

Previously, the PACIFIC trial showed that durvalumab (DURV) could become the standard-of-care treatment for patients with non–small-cell lung cancer (NSCLC) after treatment with concurrent chemoradiotherapy (cCRT) with no progression.1,2 The investigators of the COAST trial hypothesized that combination therapy with DURV plus another immunologically active monoclonal antibody would improve outcomes even further.

COAST was a phase 2 trial in which DURV alone or combined with either oleclumab (OLE) or monalizumab (MONA) was evaluated as consolidation therapy for locally advanced, unresectable, stage III NSCLC.2,3 OLE is an anti-CD73 antibody and MONA is an anti-NKG2A antibody. The expression of CD73 and NKG2A is induced by radiotherapy, thereby inhibiting antitumor immune responses. Therefore, it was hypothesized that inhibiting CD73 and NKG2A, by OLE and MONA, respectively, would be effective in antitumor activity.2

The patients studied had their tumor stage histologically and cytologically confirmed. They had a European Cooperative Oncology Group performance status score of 0/1 and had not progressed after cCRT. They were randomized to either DURV 1500 mg intravenously (IV) every 4 weeks alone or combined with OLE 3000 mg IV every 2 weeks for 2 cycles and then every 4 weeks, or MONA 750 mg IV every 2 weeks for up to 12 months, and stratified by histology.2,3

The primary end point of the study was overall response rate (ORR).3 Secondary end points were progression-free survival (PFS), safety, duration of response (DOR), disease control rate (DCR), overall survival, pharmacokinetics, and immunogenicity.2

There were 186 patients in this study; 66 were administered DURV alone, 59 received DURV plus OLE, and 61 received DURV plus MONA. Median follow-up was 11.5 months.3 ORR was 17.9% for DURV alone (95% confidence interval [CI], 9.6-29.2), 30.0% for DURV plus OLE (95% CI, 18.8-43.2), and 35.5% for DURV plus MONA (95% CI, 23.7-48.7).2 The median DOR for DURV alone was not reached (95% CI, 2.3 months-not applicable), 12.9 months for DURV plus OLE (95% CI, 6.7-not applicable), and not reached for DURV plus MONA (95% CI, 9.0 months-not applicable). The DCR was 58.2% for DURV alone (95% CI, 45.5-70.2), 81.7% for DURV plus OLE (95% CI, 69.6-90.5), and 77.4% for DURV plus MONA (95% CI, 65-87.1).2 DURV plus OLE and DURV plus MONA significantly improved PFS compared with DURV alone.3 The median PFS for DURV alone was 6.3 months, not reached for DURV plus OLE, and 15.1 months for DURV plus MONA.2

The incidence of all treatment-related adverse events (TRAEs) was 98.5% for DURV, 96.6% for DURV plus OLE, and 100% for DURV plus MONA.2 The incidence of grade ≥ 3 TRAEs (all cause) was 39.4%, 40.7%, and 27.9% with DURV, DURV plus OLE, and DURV plus MONA, respectively.2,3 Adverse events leading to treatment discontinuation occurred in 16.7%, 15.3%, and 14.8% of patients in DURV, DURV plus OLE, and DURV plus MONA, respectively.2

Pneumonia (5.9%) and decreased lymphocyte count (3.2%) were the most common grade 3/4 TRAEs. They were both more common with DURV and DURV plus OLE than with DURV plus MONA. The combined rates of pneumonitis and radiation pneumonitis of any grade were 21.2% with DURV, 28.8% with DURV plus OLE, and 21.3% with DURV plus MONA, with grade 3 events in 3.0%, 3.4%, and 1.6%, respectively.3

The researchers concluded that the combinations of DURV plus OLE and DURV plus MONA provide clinical benefit in treatment of patients with unresectable stage III NSCLC who have not progressed after cCRT. Both combinations increased ORR and improved PFS when compared with DURV alone. The safety of these combinations was manageable.2

References

  1. Faivre-Finn C, Vicente D, Kurata T, et al. Four-year survival with durvalumab after chemoradiotherapy in stage III NSCLC-an update from the PACIFIC trial. J Thorac Oncol. 2021;16:860-867.
  2. Martinez-Marti A, Majem M, Barlesi F, et al. COAST: an open-label, phase 2, multidrug platform study of durvalumab alone or in combination with novel agents in patients with locally advanced, unresectable, stage III NSCLC. Presented at: ESMO Congress 2021; September 16-21, 2021. Abstract LBA42.
  3. Martinez-Marti A, Majem M, Barlesi F, et al. LBA42 - COAST: an open-label, randomised, phase II platform study of durvalumab alone or in combination with novel agents in patients with locally advanced, unresectable, stage III NSCLC. ESMO Open. 2021;32(suppl_5):S1283-S1346.
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