LBA61 First analysis of RAIN-701: Study of tarloxotinib in patients with non-small cell lung cancer (NSCLC) EGFR Exon 20 insertion, HER2-activating mutations &amp; other solid tumours with NRG1/ERBB gene fusions

Liu, S.V.; Villaruz, Liza C.; Lee, V.H.F.; Zhu, Viola W.; Baik, Christina S.; Sacher, Adrian G.; McCoach, Caroline E.; Nguyen, Danny; Li, J.Y-C.; Pacheco, J.; Kim, C.; Burns, Timothy F.; Schenk, Erin L.; Leighl, Natasha B.; Tozzi, Lorenzo; Camidge, D. Ross

doi:10.1016/j.annonc.2020.08.2294

Cited by 63 publications

(38 citation statements)

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“…the cohort of patients with EGFRex20ins was 0% (best response, stable disease in 6/11 patients)(37). Preclinical and early clinical data have been reported supporting the efficacy of amivantamab (investigator-assessed response rate, 36%; median PFS, 8.3), an intravenous bispecific antibody that targets EGFR and MET for patients with NSCLC with EGFRex20ins and other EGFR mutations(38,39).…”

mentioning

confidence: 99%

Activity and Safety of Mobocertinib (TAK-788) in Previously Treated Non–Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations from a Phase I/II Trial

et al. 2021

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Mobocertinib, an oral epidermal growth factor receptor (EGFR) inhibitor targeting EGFR gene mutations, including exon 20 insertions (EGFRex20ins), in non–small cell lung cancer, was evaluated in a phase I/II dose-escalation/expansion trial (ClinicalTrials.gov NCT02716116). Dose escalation identified 160 mg/d as the recommended phase 2 dose and maximum tolerated dose. Among 136 patients treated with 160 mg/d, the most common any-grade treatment-related adverse events (TRAE; >25%) were diarrhea (83%), nausea (43%), rash (33%), and vomiting (26%), with diarrhea (21%) the only grade ≥3 TRAE >5%. Among 28 EGFRex20ins patients treated at 160 mg/d, the investigator-assessed confirmed response rate was 43% (12/28; 95% confidence interval, 24%–63%) with median duration of response of 14 months (5.0–not reached) and median progression-free survival of 7.3 months (4.4–15.6). Mobocertinib demonstrated antitumor activity in patients with diverse EGFRex20ins variants with a safety profile consistent with other EGFR inhibitors. Significance: No oral EGFR-targeted therapies are currently approved for patients with EGFRex20ins NSCLC. Mobocertinib demonstrated antitumor activity with manageable toxicity in patients with advanced EGFRex20ins NSCLC in this study, supporting additional development of mobocertinib in this patient population. See related commentary by Pacheco, p. 1617. This article is highlighted in the In This Issue feature, p. 1601

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confidence: 99%

Activity and Safety of Mobocertinib (TAK-788) in Previously Treated Non–Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations from a Phase I/II Trial

et al. 2021

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“…No comparative studies were identified, but rather, nine single-arm phase I/II trials (range 11–115 patients) [ 40 , 42 , 43 , 45 – 47 , 49 , 52 , 53 ] two prospective cohort studies (29 and 35 patients) [ 23 , 29 , 39 ], two pooled analyses of clinical trials (21 and 23 patients) [ 21 , 48 ], and 22 retrospective observational studies (range 15–165 patients). Half of the studies (n = 16) reported on subgroups or select cohorts of patients with Exon 20ins from studies with broader study populations, and half were conducted in Asia (n = 14), followed by the US (n = 8).…”

Section: Resultsmentioning

confidence: 99%

“…Median PFS and ORR were also more favorable for patients with Exon 20ins receiving chemotherapy (median PFS: 3.4-6.9 months for chemotherapy-based regimens [range 10-105 patients] [29,32,33,37,38] Second-or later-line clinical outcomes. Sixteen studies (reported across 21 publications) reported the clinical efficacy/effectiveness and safety of various subsequent-line treatment regimens in patients with Exon 20ins, but based on very limited sample sizes (range 11-165 patients) [10,23,24,29,30,37,[39][40][41][42][43][44][45][46][47][48][49][50][51][52][53].…”

Section: Clinical Burdenmentioning

confidence: 99%

Epidemiological and clinical burden of EGFR Exon 20 insertion in advanced non-small cell lung cancer: A systematic literature review

Burnett¹,

Emich

Carroll

et al. 2021

PLoS ONE

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Objectives The burden of epidermal growth factor receptor (EGFR) exon 20 insertion mutation (Exon 20ins) in non-small cell lung cancer is not well understood. A systematic review was conducted to identify evidence on mutation frequency, prognostic impact, clinical, patient-reported, and economic outcomes associated with Exon 20ins. Materials and methods Searches were conducted in Embase and Medline and supplemented with recent conference proceedings. Included studies were not limited by intervention, geography, or publication year. Results Seventy-eight unique studies were included; 53 reporting mutation frequency, 13 prognostic impact, 36 clinical outcomes, and one humanistic burden. No economic burden data were identified. The frequency of Exon 20ins mutation ranged from 0.1% to 4% of all NSCLC cases and 1% to 12% of all EGFR mutations. Data on the prognostic impact of Exon 20ins were heterogeneous but highlighted poorer outcomes in patients with Exon 20ins mutation compared with patients with other EGFR mutations and EGFR wildtype across a wide range of therapies and treatment lines. Comparative evidence on the clinical efficacy and safety of currently available therapies were limited, as were sample sizes of studies reporting on real-world effectiveness. Nine single-arm trials and 27 observational studies reported clinical outcomes for patients with Exon 20ins. Trends towards better survival and response were observed for chemotherapy compared with TKIs as first-line treatments. For subsequent treatment lines, novel targeted therapies provided encouraging preliminary responses while results for chemotherapy were less favorable. Limited safety data were reported. One conference abstract described the symptom burden for Exon 20ins patients with fatigue and pain being most common. Conclusion Findings of the systematic review show a high unmet need for safe and efficacious treatments for patients with Exon 20ins as well and need for further evidence generation to better understand the patient-level and economic impact for these patients.

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“…Median PFS was 4.2 months in the intent-to-treat population. No clinical activity (ORR 0%) was detectable for tarloxotinib, another selective EGFR exon 20 inhibitor, which has been evaluated in the RAIN-701 trial [ 125 ].…”

Section: Egfr Mutationsmentioning

confidence: 99%

“…Poziotinib showed a manageable safety profile with diarrhea (26%), rash (30%) and stomatitis (22%) as most common grade 3 adverse events. First results of the RAIN-701 trial assessing the hypoxia activated pan-HER inhibitor tarloxotinib in NSCLC and other solid tumors have been presented at the virtual 2020 ESMO congress [ 125 ]. Among the 9 evaluable patients with HER2 exon 20 insertion mutated NSCLC, the ORR was 22%.…”

Section: Her2 Alterationsmentioning

confidence: 99%

Targeted Therapy in Advanced and Metastatic Non-Small Cell Lung Cancer. An Update on Treatment of the Most Important Actionable Oncogenic Driver Alterations

König

Prince

Rothschild

2021

Cancers

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Due to groundbreaking developments and continuous progress, the treatment of advanced and metastatic non-small cell lung cancer (NSCLC) has become an exciting, but increasingly challenging task. This applies, in particular, to the subgroup of NSCLC with oncogenic driver alterations. While the treatment of epidermal growth factor receptor (EGFR)-mutated and anaplastic lymphoma kinase (ALK)-rearranged NSCLC with various tyrosine kinase inhibitors (TKIs) is well-established, new targets have been identified in the last few years and new TKIs introduced in clinical practice. Even for KRAS mutations, considered for a long time as an “un-targetable” alteration, promising new drugs are emerging. The detection and in-depth molecular analysis of resistance mechanisms has further fueled the development of new therapeutic strategies. The objective of this review is to give a comprehensive overview on the current landscape of targetable oncogenic alterations in NSCLC.

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LBA61 First analysis of RAIN-701: Study of tarloxotinib in patients with non-small cell lung cancer (NSCLC) EGFR Exon 20 insertion, HER2-activating mutations & other solid tumours with NRG1/ERBB gene fusions

Cited by 63 publications

References 0 publications

Activity and Safety of Mobocertinib (TAK-788) in Previously Treated Non–Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations from a Phase I/II Trial

Activity and Safety of Mobocertinib (TAK-788) in Previously Treated Non–Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations from a Phase I/II Trial

Epidemiological and clinical burden of EGFR Exon 20 insertion in advanced non-small cell lung cancer: A systematic literature review

Targeted Therapy in Advanced and Metastatic Non-Small Cell Lung Cancer. An Update on Treatment of the Most Important Actionable Oncogenic Driver Alterations

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