VHIO at ESMO 2021: the promise of potential new therapeutic avenues against NSCLC

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Featuring among our pre-selection pick of VHIO (co) led research (1) that has subsequently headlined during this week’s virtual 2021 annual Congress of the European Society for Medical Oncology (ESMO), 18-21 September, are two important contributions reporting treatment advances against non-small-cell lung cancer.

Delivering on the promise of immune-based therapy in lung cancer

In addition to exciting data  from the phase III multicenter IMpower010, that were presented by VHIO’s Enriqueta Felip (2), Principal Investigator of our Thoracic Tumors & Head and Neck Group, and Head of the Thoracic Cancer Unit at the Vall d’Hebron (VHIO’s dedicated news here), results from the COAST phase II open-label, multicenter, randomized multidrug platform trial also headlined during the meeting (3).

Selected by ESMO as a Late Breaker, this study was designed to assess the efficacy and safety of the anti-PD-L1 monoclonal antibody, durvalumab, alone versus durvalumab in combination with novel agents in patients with locally advanced, unresectable, stage III non-small cell lung cancer (NSCLC), who have not progressed after concurrent chemoradiotherapy (cCRT).

Presented by Alexandre Martínez-Martí, a Medical Oncologist and Clinical Investigator of Enriqueta Felip’s team, findings revealed that durvalumab administered in combination with the monoclonal antibodies, oleclumab, as well as monalizumab, could increase clinical activity in this particular patient population.

Specifically, the COAST investigators found that both combinations led to an increase in overall response rates (ORR) compared to durvalumab as monotherapy. “Although the objective response rate shows median early clinical activity, the rate of progression-free survival was more significant. Of note, with the early separation of the survival curves, our data showed that PFS at ten months significantly improved with both combinations compared to durvalumab alone,” said Alexandre Martínez-Martí, lead author of the study.

He added, “We observed that the safety profile of both experimental combinations was similar to that of durvalumab alone. Collectively, in view of the small data set, our results should be tentatively considered.”  Delivering powerful blows against NSCLC: HER2 antibody-drug conjugate, trastuzumab deruxtencan, steps up as a powerful contender Presented during a Proffered Paper session (4) by Bob T. Li, a Medical Oncologist and Physician-Scientist at the Memorial Sloan Kettering Cancer Center (MSKCC), New York (USA), primary data of the multicenter, international, DESTINY-Lung01 phase II trial, also made headlines during the ESMO21 Congress.

This pivotal study, co-authored by VHIO’s Enriqueta Felip, was designed to assess the efficacy and safety of the HER2 antibody-drug conjugate (ADC), trastuzumab deruxtencan, in patients with HER2-mutant NSCLC. “While this ADC has shown spectacular results in the treatment of HER2-positive breast cancer, trastuzumab deruxtencan has not been extensively investigated as a new therapeutic avenue for NSCLC patients. Up until now,” observed Enriqueta Felip, a DESTINY-Lung01 Investigator. Published in parallel in The New England Journal of Medicine (5), results showed that treatment with this ADC achieved a response rate of up to 54% across different HER2 mutation subtypes, as well as in patients with no detectable HER2 expression or HER2 amplification. “Progression-free survival increased by 8.2 months, with a median survival rate of 18 months, and the observed toxicity was generally consistent with those in previously reported studies,” noted Enriqueta Felip.

She concluded, “The results of this study are as striking as they are timely. Up until now, no other approved novel therapy has been available for patients with previously treated HER2-mutant NSCLC.” 

Reflective of her internationally renowned expertise in the field of lung cancer and thoracic tumors, Enriqueta Felip serves on the International Association for the Study of Lung Cancer’s (IASLC)  Board of Directors (2019-2021) as Secretary.

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References:

[1] VHIO News: https://www.vhio.net/esmos-2021-virtual-congress-16-21-september-a-pick-of-vhio-research-highlights/.

[2] LBA9 – IMpower010: Sites of relapse and subsequent therapy from a phase III study of atezolizumab vs best supportive care after adjuvant chemotherapy in stage IB-IIIA NSCLC, was presented by Enriqueta Felip during Presidential Symposium on Monday 20 September 2021, 15:05-16:35 (CEST), Channel 1.

The results of this study published simultaneously in The Lancet:

  1. Felip, E. Vallieres, C. Zhou, H. Wakelee, I. Bondarenko, H. Sakai, H. Saito, G. Ursol, K. Kawaguchi9, Y. Liu, E. Levchenko, N. Kislov, M. Reck, R. Liersch, V.A. McNally, Q. Zhu, B. Ding, E. Bennett, B. Gitlitz, N.K. Altorki. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small cell lung cancer (IMpower010): a randomised, open-label phase 3 trial. The Lancet. Published: September 20, 2021 DOI: 10.1016/S0140-6736(21)02098-5.

[3] 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. The data from this study were presented by Alex Martínez during the Proffered Paper Session – Non-metastatic NSCLS and other thoracic malignancies,  on Friday 17 September 2021, 13:30-14:50h (CEST), Channel 2.

[4] LBA45 – Primary data from DESTINY-Lung01: A phase II trial of trastuzumab deruxtecan (T-DXd) in patients (Pts) with HER2-mutated (HER2m) metastatic non-small cell lung cancer (NSCLC), were presented by Bob T. Li during a Proffered Paper Session – NSCLC, metastatic 1, on Saturday, 18 September 2021, 13:30- 14:50h (CEST), Channel 1.

[5] Li BT, Smit EF, Goto Y, Nakagawa K, Udagawa H, Mazières J, Nagasaka M, Bazhenova L, Saltos AN, Felip E, Pacheco JM, Pérol M, Paz-Ares L, Saxena K, Shiga R, Cheng Y, Acharyya S, Vitazka P, Shahidi J, Planchard D, Jänne PA; DESTINY-Lung01 Trial Investigators. Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer. N Engl J Med. 2021 Sep 18. doi: 10.1056/NEJMoa2112431. Epub ahead of print. PMID: 34534430.

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