SHERLOCK Protocol number: CTC 0377 / TOGA 21/011
Phase 2 trial of sotorasib in combination with carboplatin-pemetrexed and bevacizumab-biosimilar as first line treatment for advanced non-squamous non-small cell lung cancer with KRAS G12C mutation.
- Adults, aged 18 years and older, with either:
a) newly diagnosed, treatment naïve metastatic (Stage IV) non-squamous NSCLC, or
b) recurrent non-squamous NSCLC with no disease progression for at least 6 months following prior curative lung surgery and (neo)adjuvant chemotherapy, or prior curative concurrent chemoradiotherapy and immunotherapy maintenance, for non-resectable stage III cancer.
- Presence of KRAS G12C mutation in tumour tissue
- Sufficient tumour tissue should be available for molecular profiling by Next Generation Sequencing (NGS) or results available from molecular profiling of tumour tissue by NGS. If there is insufficient tissue for NGS testing, a repeat biopsy is strongly recommended. Acceptable platforms include, but are not limited to: FoundationOne Tissue CDx, Illumina TruSight Oncology 500 (TSO500)
- Measurable disease according to RECIST 1.1. Lesions previously irradiated are not considered measurable unless they have unequivocally progressed after radiation.
- ECOG performance status of 0 or 1
- Adequate organ function
Key Exclusion Criteria:
- Previous treatment with sotorasib, or KRAS G12C specific inhibitor, or pan-KRAS inhibitor
- Concurrent driver mutation (including EGFR, ALK, ROS1, BRAF) where an approved targeted therapy is available
- Mixed histology with any small cell or squamous component
- Evidence of active bleeding or bleeding risk
- Significant cardiovascular disease, peripheral vascular disease or cerebrovascular disease
- Severe infection within 4 weeks prior to registration including, but not limited to hospitalisation for management of infection, bacteraemia or sepsis.
- Spinal cord compression, symptomatic and unstable brain metastases, except for those participants who have completed definitive therapy, are not on steroids equivalent to oral prednisone of > 10 mg/day, and have a stable neurological status for at least 2 weeks after commencement of the definitive therapy. Participants with untreated asymptomatic brain metastases can be eligible for inclusion if immediate definitive treatment is not indicated
- Life expectancy of less than 3 months
The new drug, sotorasib, is a tablet treatment which is targeted against the KRAS G12C gene mutation. Early results show that sotorasib is moderately active when given alone. The effectiveness of sotorasib might be increased when given in combination with other anti-cancer drugs. This study will investigate whether sotorasib used in combination with two chemotherapy drugs (called carboplatin and pemetrexed) and bevacizumab (which improves anti-cancer drug delivery), can result in better outcomes. The combination of carboplatin-pemetrexed-bevacizumab is a proven treatment for NSCLC.