CodeBreak 100: Sotorasib in KRAS p.G123C NSCLC

Outcomes in patients with advanced non-small cell lung cancer (NSCLC) are generally poor, but advances in the knowledge of pathways and targetable oncogenes have paved the way for targeted therapies in specific patient populations. One of the most exciting updates reported at the recent World Conference on Lung Cancer (WCLC) virtual meeting was the results from the CodeBreak 100 study (NCT03600883), which evaluated the efficacy of sotorasib. This first-in-class molecule specifically and irreversibly inhibits KRAS G12C – one of the most prevalent driver mutations, present in around 13% of lung adenocarcinomas.

Following on from a successful Phase I study, Bob T. Li, MD, PhD, MPH, Memorial Sloan Kettering Cancer Center, New York, NY, presented results from the Phase II trial at WCLC. In this international, single-arm study, patients with advanced or metastatic NSCLC were administered with sotorasib 960 mg OD (N=126). Patients were included if they had received at lease 3 prior lines of therapy, and the primary endpoint was confirmed objective response rate (ORR).

 

Based on from the results of CodeBreak 100, the Food and Drug Administration (FDA) has granted sotorasib with Priority Review for the treatment of patients with KRAS G12C-mutated locally advanced or metastatic NSCLC following at least one prior systemic therapy.

Breakthrough in treating patients with mesothelioma

Since 2004, there have been no advances in the treatment of mesothelioma that have shown an improvement in overall survival (OS) after standard front-line chemotherapy (pemetrexed + cisplatin/carboplatin). Following surgery, chemotherapy and radiotherapy, the current next treatment option for patients is enrolment into a clinical trial or palliative care. Therefore, the unmet need for these patients is staggering.

At the recent WCLC meeting, Dean Fennell, PhD, FRCP, University Hospitals of Leicester NHS Trust, Leicester, UK, presented results from the Stand Up To Cancer Research UK CONFIRM study (NCT03063450). This Phase III randomized (2:1), placebo-controlled study evaluated the efficacy and safety of nivolumab, a PD-1 inhibitor, in patients with previously treated, unresectable malignant mesothelioma.

Patients received nivolumab (3 mg/kg; n=221) or placebo (n=111) once every 2 weeks until disease progression or up to 12 months. Co-primary endpoints reported were progression-free survival (PFS) and overall survival (OS).

The exciting results reported from the CONFIRM study provide hope to patients with malignant mesothelioma.

KEYNOTE-598: pembrolizumab monotherapy remains standard-of-care as first-line therapy for metastatic NSCLC

The successful introduction of immune checkpoint inhibitors into the treatment armamentarium for lung cancer have shown remarkable efficacy. Several studies have shown improved survival with these therapies – as monotherapy or in combination with chemotherapy.

The KEYNOTE-598 (NCT03302234) study set out to evaluate whether adding ipilimumab, an immune checkpoint inhibitor targeting CTLA-4, to pembrolizumab, an anti-PD1 antibody, would improve efficacy over pembrolizumab alone in patients with a PD-L1 tumor proportion score (TPS) ≥50%.

Michael Boyer, MBBS, FRACP, PhD, Chris O’Brien Lifehouse, Camperdown, NSW, Australia presented results from the study which randomized patients 1:1 to ipilimumab 1 mg/kg Q6W or saline placebo for up to 18 cycles – patients in both arms received pembrolizumab 200 mg Q3W for up to 35 cycles. The primary endpoints reported were overall survival (OS) and progression-free survival (PFS).

The results of this study confirmed pembrolizumab monotherapy as a standard-of-care for this patient population.

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