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An Expert’s Guide to WCLC 2020: A Preview of the Top Abstracts

Shirish M. Gadgeel, MD

Division of Hematology/Oncology
Department of Internal Medicine
Henry Ford Cancer Institute
Henry Ford Health System
Detroit, Michigan

Shirish M. Gadgeel, MD, has disclosed that he has received consulting fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Pfizer, Roche/Genentech, and Takeda; fees for non-CME/CE services from Merck Sharp & Dohme and Xcovery; and other financial or material support from AstraZeneca and Roche/Genentech.

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Nicolas Girard, MD, PhD

Université Paris-Saclay
Head of the Thorax Institute Curie-Montsouris
Institut Curie
Paris, France

Nicolas Girard, MD, PhD, has disclosed that he has received consulting fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, PharmaMar, Roche, Sanofi, and Teva, and funds for research support from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, and Roche.

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Released: January 26, 2021

During the 2020 World Conference on Lung Cancer (WCLC), which is being held virtually January 28-31, 2021, important findings from many clinical trials focused on lung cancer and other thoracic malignancies will be reported. Below, experts have highlighted their most anticipated abstracts, which will be covered online as a part of CCO’s Independent Conference Coverage of WCLC 2020. As the WCLC meeting unfolds, remember to check back on the CCO Web site for a downloadable highlights slideset summarizing the data from these studies and more, and then again after the meeting for a CME-certified online expert analysis featuring discussions and perspectives on the clinical implications of the new data.

Here, experts Shirish Gadgeel, MD, and Nicolas Girard, MD, PhD, have identified several key studies with the potential to change clinical practice in lung cancer, as well as additional studies that may be of clinical interest.

Top Picks: Non-Small-Cell Lung Cancer (NSCLC)
At the Presidential Symposium, the highly anticipated results from the phase II portion of the CodeBreaK 100 study, evaluating the oral inhibitor sotorasib (previously AMG 510) in advanced NSCLC with the KRASG12C mutation, will be presented. Previous data from the phase I/II portion of this study suggested that sotorasib was well tolerated and yielded an ORR of 32.2% for all patients across evaluated dose levels.

Sabari and colleagues will report updated results from the CHRYSALIS study of amivantamab, a novel fully human EGFR-MET bispecific antibody with immune cell–directing activity, in patients with EGFR- and MET-mutant NSCLC from the cohort of patients with EGFR exon 20 insertion mutations who were treated at the recommended phase II dose (RP2D) and had previously received platinum-based chemotherapy in frontline. Data from the available abstract suggest promising efficacy and durable responses as well as a manageable safety profile in more than 250 patients treated at the RP2D. Zhou and colleagues will report data from the phase I/II EXCLAIM study evaluating mobocertinib, a potent first-in-class tyrosine kinase inhibitor (TKI) targeting EGFR exon 20 insertion mutations, including first results from the extension cohort and results in patients who received previous platinum-based therapy from the dose-escalation/expansion cohorts and the extension cohort of the study. Moreover, Girard and colleagues will present comparative clinical outcomes for patients with NSCLC harboring EGFR exon 20 insertion mutations and common EGFR mutations, suggesting patients with EGFR exon 20 insertion mutations have a poorer prognosis—higher disease progression and mortality—due to the lack of effective treatment options in this subset of patients vs those with common EGFR mutations.

In the setting of EGFR-mutant NSCLC failing previous EGFR TKIs and platinum-based chemotherapy, Yu and colleagues will report on the safety and activity of patritumab deruxtecan, a HER3-directed antibody–drug conjugate (ADC) from a phase I trial.This study is evaluating patritumab deruxtecan at the recommended dose for expansion of 5.6 mg/kg in 57 patients with heavily pretreated locally advanced or metastatic EGFR-mutant NSCLC. The abstract suggests that, at the 5.6-mg/kg dose, patritumab deruxtecan shows promising antitumor activity and safety in this patient population. Spira and colleagues will present updated results of the phase I TROPION-PanTumor01 study of datopotamab deruxtecan, an anti-TROP2 ADC, in patients with advanced NSCLC. The abstract for this study reports encouraging antitumor activity for datopotamab deruxtecan across all doses tested in previously treated patients with progression on standard treatment, along with a manageable safety profile. Nakagawa and colleagues will report interim efficacy and safety results from the phase II DESTINY-Lung01 study of trastuzumab deruxtecan in the cohort of patients with HER2-overexpressing (centrally confirmed IHC 2+ or 3+) NSCLC exhibiting evidence of antitumor activity in this heavily pretreated patient population. The abstract for that study reports that treatment-related interstitial lung disease remains a serious adverse event, which requires proactive monitoring and management.

Data from several trials evaluating the use of immunotherapy in lung cancer will also be presented at the WCLC 2020 meeting. Ali and colleagues will present data from the phase III KEYNOTE-598 study evaluating efficacy of pembrolizumab plus ipilimumab in patients with previously untreated metastatic NSCLC who have a PD-L1 tumor proportion score of ≥ 50%. Lai and colleagues will report on the randomized phase II study of nivolumab with or without ipilimumab in patients with EGFR-mutated NSCLC who failed 1 previous line of standard anti-EGFR TKI therapy. Kilickap and colleagues report the results of a post hoc analysis of the phase III EMPOWER-Lung 1 trial evaluating cemiplimab vs platinum-doublet chemotherapy as a frontline treatment in 437 patients with advanced NSCLC with a PD-L1 level ≥ 50%. Data from the available abstract suggest treatment with cemiplimab is superior to platinum-based chemotherapy in terms of ORR, PFS, and OS, which was associated with increases in PD-L1 expression.

In early-stage, EGFR mutation–positive NSCLC, the patient-reported outcomes analyses and postoperative chemotherapy use and outcomes from the phase III ADAURA study of adjuvant osimertinib vs placebo in resected EGFR-mutant NSCLC will be presented. Of importance, the benefit of adjuvant osimertinib following adjuvant chemotherapy was not detailed in previous reports. ADAURA has changed the standard of care for patients with resected EGFR mutation–positive NSCLC. In a previous report of the ADAURA study, adjuvant osimertinib in resected stage IB/II/IIIA NSCLC was shown to significantly lower the risk of recurrence (HR: 0.21; P < .001) and improve the disease-free survival rate (HR: 0.17; P < .0001), which led to FDA approval of osimertinib as adjuvant therapy after tumor resection in EGFR-altered (exon 19 deletion or exon 21 L858R mutations) NSCLC. In addition, final results from the multicenter phase III ITACA trial of adjuvant pharmacogenomic-driven chemotherapy vs standard adjuvant chemotherapy in resected stage II-IIIA NSCLC will be presented.

Additional studies to watch in NSCLC:

  • Study of the predictive value of comutations in DNA damage repair pathways in patients receiving atezolizumab or docetaxel (Abstract OA07.03)
  • Retrospective analysis of the interdependence of KRAS and TP53 mutations in predicting immune checkpoint inhibition efficacy in EGFR/ALK-positive NSCLC (Abstract OA07.06)
  • Initial experience of hybrid operating room cone-beam CT-guided bronchoscopic microwave thermal ablation of peripheral small lung lesions (Abstract MA02.04)
  • Randomized phase II RTOG1106 trial of midtreatment PET/CT-guided adaptive radiotherapy in locally advanced NSCLC (Abstract OA02.04)

Top Picks: Small-Cell lung Cancer (SCLC)
In relapsed limited-stage or extensive-stage SCLC, Paz-Ares and colleagues will report data from part 1 of the phase II/III RESILIENT study evaluating liposomal irinotecan at either 85 mg/m2 or 70 mg/m2 every 2 weeks in 30 patients 18 years of age or older who had progressed on previous platinum-based frontline therapy and had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0/1. Complete results will be presented at the meeting. Also in relapsed limited-stage or extensive-stage SCLC, Ponce-Aix and colleagues will present data on the antitumor activity and safety from the expansion stage of a phase I/II study of lurbinectedin plus irinotecan in 21 patients with advanced SCLC who had up to 2 previous lines of chemotherapy and ECOG PS of 0/1. The online abstract for that study suggests encouraging efficacy, with remarkable antitumor activity observed in patients with platinum-resistant disease, and a manageable safety profile consisting of hematologic abnormalities, diarrhea, and fatigue. In patients with recurrent or progressing SCLC after at least 1 platinum-based chemotherapy, Owonikoko and colleagues will report emerging data from a phase I study of AMG 757, a half-life extended bispecific antibody targeting DLL3 on tumor cells and CD3 on T-cells.

Top Picks in Malignant Mesothelioma
In the Presidential Symposium, Fennell and colleagues will present data from the randomized, double-blind phase III CONFIRM trial of nivolumab vs placebo as third-line or fourth-line therapy for patients with malignant mesothelioma that has relapsed after platinum-based chemotherapy. The coprimary endpoints for that study are OS (defined as time from randomization to death from any cause) and PFS (per modified RECIST or RECIST 1.1; from time of randomization to progression, and assessed for up to 51 months).

Remember to Check the CCO Web Site After WCLC 2020!
These are just a few of the interesting and important abstracts selected by our expert faculty from WCLC 2020. A downloadable highlight slideset of these studies and more will be available on our Web site after the data are presented. Also after the meeting, a comprehensive analysis by our expert faculty members will explore the clinical implications of the data in a CME-certified text-based module.

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