On May 28, 2021, the Food and Drug Administration granted accelerated approval to sotorasib, a RAS GTPase family inhibitor, for adult patients with KRAS G12C ‑mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA ‑approved test, who have received at least one prior systemic therapy.

FDA also approved the QIAGEN therascreen® KRAS RGQ PCR kit (tissue) and the Guardant360® CDx (plasma) as companion diagnostics for sotorasib. If no mutation is detected in a plasma specimen, the tumour tissue should be tested.

Approval was based on CodeBreaK 100, a multi-centre, single-arm, open label clinical trial (NCT03600883) which included patients with locally advanced or metastatic NSCLC with KRAS G12C mutations.

Efficacy was evaluated in 124 patients whose disease had progressed on or after at least one prior systemic therapy.

Patients received sotorasib 960 mg orally daily until disease progression or unacceptable toxicity.

The main efficacy outcome measures were objective response rate (ORR) according to RECIST 1.1, as evaluated by blinded independent central review and response duration. The ORR was 36% (95% CI: 28%, 45%) with a median response duration of 10 months (range 1.3+, 11.1).

The most common adverse reactions (≥ 20%) were diarrhoea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough.

The most common laboratory abnormalities (≥ 25%) were decreased lymphocytes, decreased haemoglobin, increased aspartate aminotransferase, increased alanine aminotransferase, decreased calcium, increased alkaline phosphatase, increased urine protein, and decreased sodium.

The recommended sotorasib dose is 960 mg orally once daily with or without food.

The approved 960 mg dose is based on available clinical data, as well as pharmacokinetic and pharmacodynamic modelling that support the approved dose. As part of the evaluation for this accelerated approval, FDA is requiring a postmarketing trial to investigate whether a lower dose will have a similar clinical effect.

View full prescribing information here.

Source: FDA