Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer.

Background: Neoadjuvant or adjuvant immunotherapy can improve outcomes in patients with resectable non-small-cell lung cancer (NSCLC). Perioperative regimens may combine benefits of both to improve long-term outcomes.

Methods: We randomly assigned patients with resectable NSCLC (stage II to IIIB [N2 node stage] according to the eighth edition of the ) to receive platinum-based chemotherapy plus durvalumab or placebo administered intravenously every 3 weeks for 4 cycles before surgery, followed by adjuvant durvalumab or placebo intravenously every 4 weeks for 12 cycles.

Phase IIa Study of PLX2853 in Gynecologic Cancers With Known ARID1A Mutation and Phase Ib/IIa Study of PLX2853/Carboplatin in Platinum-Resistant Epithelial Ovarian Cancer.

Purpose: The Bromodomain and Extra-Terminal (BET) domain proteins facilitate the development of many human cancers via epigenetic regulation. BET inhibitors may be effective in reversing platinum resistance in ovarian cancer (OC) and may generate synthetic lethality with loss. PLX2853 is an orally active, small-molecule inhibitor of BET bromodomain-mediated interactions that exhibits low nanomolar potency in blocking all four BET family members.

Early Changes in Circulating Cell-Free KRAS G12C Predict Response to Adagrasib in KRAS Mutant Non-Small Cell Lung Cancer Patients.

Purpose: Non-invasive monitoring of circulating tumor DNA (ctDNA) has the potential to be a readily available measure for early prediction of clinical response. Here, we report on early ctDNA changes of KRAS G12C in a Phase 2 trial of adagrasib in patients with advanced, KRAS G12C-mutant lung cancer.

Experimental Design: We performed serial droplet digital PCR (ddPCR) and plasma NGS on 60 KRAS G12C-mutant patients with lung cancer that participated in cohort A of the KRYSTAL-1 clinical trial.

Brief Report: Safety and Antitumor Activity of Durvalumab Plus Tremelimumab in Programmed Cell Death-(Ligand)1-Monotherapy Pretreated, Advanced NSCLC: Results From a Phase 1b Clinical Trial.

Introduction: Although first-line immunotherapy approaches are standard, in patients with non-small cell lung cancer (NSCLC) previously treated with programmed cell death protein-1 or programmed death-(ligand)1 (PD-[L]1) inhibitors, the activity of combined CTLA-4 plus PD-(L)1 inhibition is unknown. This phase 1b study evaluated the safety and efficacy of durvalumab plus tremelimumab in adults with advanced NSCLC who received anti-PD-(L)1 monotherapy as their most recent line of therapy.

Methods: Patients with PD-(L)1-relapsed or refractory NSCLC were enrolled between October 25, 2013, and September 17, 2019.

Adagrasib: a novel inhibitor for -mutated non-small-cell lung cancer.

Adagrasib is a recently US FDA-approved novel targeted therapy with clinical efficacy in patients with advanced, pretreated -mutated non-small-cell lung cancer. KRYSTAL-I reported an objective response rate of 42.9% with median duration of response of 8.

Management of infusion-related reactions (IRRs) in patients receiving amivantamab in the CHRYSALIS study.

Background: Amivantamab, a fully humanized EGFR-MET bispecific antibody, has antitumor activity in diverse EGFR- and MET-driven non-small cell lung cancer (NSCLC) and a safety profile consistent with associated on-target activities. Infusion-related reaction(s) (IRR[s]) are reported commonly with amivantamab. We review IRR and subsequent management in amivantamab-treated patients.

Phase I trial of ATM inhibitor M3541 in combination with palliative radiotherapy in patients with solid tumors.

Background: Ataxia telangiectasia mutated (ATM) kinase orchestrates DNA double strand break (DSB) repair; ATM inhibitors may therefore enhance the therapeutic effect of DSB-inducing treatments such as radiotherapy (RT). M3541 is an orally administered selective inhibitor of ATM.

Methods: This phase I dose-escalation study evaluated the maximum-tolerated dose (MTD), recommended phase II dose(s) (RP2D), safety, pharmacokinetics (PK) and antitumor activity of M3541 in combination with fractionated palliative RT in patients with solid tumors.

A phase 1b study evaluating the safety and preliminary efficacy of berzosertib in combination with gemcitabine in patients with advanced non-small cell lung cancer.

Objectives: Berzosertib (formerly M6620, VX-970) is an intravenous, highly potent and selective, first-in-class ataxia telangiectasia and Rad3-related (ATR) protein kinase inhibitor. We assessed the safety, tolerability, preliminary efficacy, and pharmacokinetics (PK) of berzosertib plus gemcitabine in an expansion cohort of patients with advanced non-small cell lung cancer (NSCLC). The association of efficacy with TP53 status and other tumor markers was also explored.

Targeted Treatment of Non-Small Cell Lung Cancer: Focus on Capmatinib with Companion Diagnostics.

dysregulation promoting tumorigenesis in non-small cell lung cancer (NSCLC) is associated with worse outcomes following chemotherapy as compared to non-driver mutated NSCLC and occurs either through mutations causing exon 14 skipping (ex14) or gene amplification and overexpression that result in enhanced receptor signaling. Capmatinib is the first FDA-approved targeted therapy for NSCLC with ex14 skipping mutations, approved in 2020. FoundationOne CDx, a comprehensive genomic profiling test for solid tumors, was concurrently approved as a companion diagnostic for capmatinib use.

Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study.

Purpose: Non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor () exon 20 insertion (Exon20ins) mutations exhibits inherent resistance to approved tyrosine kinase inhibitors. Amivantamab, an EGFR-MET bispecific antibody with immune cell-directing activity, binds to each receptor's extracellular domain, bypassing resistance at the tyrosine kinase inhibitor binding site.

Methods: CHRYSALIS is a phase I, open-label, dose-escalation, and dose-expansion study, which included a population with Exon20ins NSCLC.

Camidanlumab tesirine in patients with relapsed or refractory lymphoma: a phase 1, open-label, multicentre, dose-escalation, dose-expansion study.

Background: Novel approaches are required to improve outcomes in relapsed or refractory classical Hodgkin lymphoma and non-Hodgkin lymphoma. We aimed to evaluate camidanlumab tesirine, an anti-CD25 antibody-drug conjugate, in this patient population.

Methods: This was a phase 1, dose-escalation (part 1), dose-expansion (part 2), multicentre trial done in 12 hospital sites (seven in the USA and five in the UK).

Patient-reported outcomes with durvalumab by PD-L1 expression and prior chemoradiotherapy-related variables in unresectable stage III non-small-cell lung cancer.

We retrospectively investigated the impact of tumor PD-L1 expression and prior chemoradiotherapy (CRT)-related variables on patient-reported outcomes (PROs) from PACIFIC. PACIFIC was a Phase III study of durvalumab versus placebo after CRT in patients with unresectable, stage III non-small-cell lung cancer. If available, pre-CRT tumor tissue was tested for PD-L1 tumor-cell expression, scored at prespecified (25%) and (1%) cut-offs.

Multicenter Phase I Study of Erdafitinib (JNJ-42756493), Oral Pan-Fibroblast Growth Factor Receptor Inhibitor, in Patients with Advanced or Refractory Solid Tumors.

Purpose: Here, we report results of the first phase I study of erdafitinib, a potent, oral pan-FGFR inhibitor.

Patients And Methods: Patients age ≥18 years with advanced solid tumors for which standard antineoplastic therapy was no longer effective were enrolled (NCT01703481). Parts 2 to 4 employed molecular screening for activating genomic alterations.

Brigatinib versus Crizotinib in ALK-Positive Non-Small-Cell Lung Cancer.

Background: Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, has robust efficacy in patients with ALK-positive non-small-cell lung cancer (NSCLC) that is refractory to crizotinib. The efficacy of brigatinib, as compared with crizotinib, in patients with advanced ALK-positive NSCLC who have not previously received an ALK inhibitor is unclear.

Methods: In an open-label, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with advanced ALK-positive NSCLC who had not previously received ALK inhibitors to receive brigatinib at a dose of 180 mg once daily (with a 7-day lead-in period at 90 mg) or crizotinib at a dose of 250 mg twice daily.

Cell-Free DNA Next-Generation Sequencing Prediction of Response and Resistance to Third-Generation EGFR Inhibitor.

Introduction: The genomic alterations driving resistance to third-generation EGFR tyrosine kinase inhibitors (TKIs) are not well established, and collecting tissue biopsy samples poses potential complications from invasive procedures. Cell-free circulating DNA (cfDNA) testing provides a noninvasive approach to identify potentially targetable mechanisms of resistance. Here we utilized a 70-gene cfDNA next-generation sequencing test to interrogate pretreatment and progression samples from 77 EGFR-mutated non-small cell lung cancer (NSCLC) patients treated with a third-generation EGFR TKI.

Product review on the Anti-PD-L1 antibody atezolizumab.

Immunotherapy as a therapeutic strategy has seized the narrative throughout clinical oncology over the past few years. Once considered a niche treatment for rare cancers, immunotherapy has quickly emerged as the standard of care for many common cancer types. The remarkable rise is largely due to the development of novel checkpoint inhibitors, specifically, antibodies targeting PD-1 and PD-L1.

Efficacy and Safety Results of the Afatinib Expanded Access Program.

Introduction: Afatinib is an oral, irreversible ErbB family blocker approved for first-line treatment of metastatic epidermal growth factor receptor () mutation-positive non-small cell lung cancer (NSCLC). The expanded access program (EAP) allowed early access to afatinib and provided additional data on its safety, tolerability, and efficacy.

Methods: The afatinib EAP was an open-label, multicenter, single-arm program in the United States that treated and followed patients with locally advanced or metastatic NSCLC harboring mutations.

Bevacizumab plus paclitaxel versus placebo plus paclitaxel as first-line therapy for HER2-negative metastatic breast cancer (MERiDiAN): A double-blind placebo-controlled randomised phase III trial with prospective biomarker evaluation.

Aim: MERiDiAN evaluated plasma vascular endothelial growth factor-A (pVEGF-A) prospectively as a predictive biomarker for bevacizumab efficacy in metastatic breast cancer (mBC).

Methods: In this double-blind placebo-controlled randomised phase III trial, eligible patients had HER2-negative mBC previously untreated with chemotherapy. pVEGF-A was measured before randomisation to paclitaxel 90 mg/m on days 1, 8 and 15 with either placebo or bevacizumab 10 mg/kg on days 1 and 15, repeated every 4 weeks until disease progression, unacceptable toxicity or consent withdrawal.