Jan 2023: Adagrasib (Krazati, Mirati Therapeutics, Inc.), a RAS GTPase family inhibitor, was given accelerated approval by the Food and Drug Administration (FDA) for adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as identified by an FDA-approved test, who have received at least one prior systemic therapy.
As additional companion diagnostics for Krazati, the FDA additionally approved the QIAGEN therascreen KRAS RGQ PCR kit (tissue) and the Agilent Resolution ctDx FIRST Assay (plasma). The tumour tissue should be examined if there was no indication of a mutation in the plasma sample.
The KRYSTAL-1 clinical trial (NCT03785249), which involved patients with locally advanced or metastatic NSCLC with KRAS G12C mutations, served as the foundation for the approval. Efficacy was assessed in 112 individuals whose illness had advanced during or after receiving immune checkpoint inhibitors and platinum-based chemotherapy, either concurrently or sequentially. Patients got adagrasib 600 mg twice daily until their condition progressed or the side effects became intolerable.
The primary efficacy outcome measures were duration of response and confirmed objective response rate (ORR) in accordance with RECIST 1.1, as assessed by a blinded independent central review (DOR). The median DOR was 8.5 months (95% CI: 6.2, 13.8), and the ORR was 43% (95% CI: 34%, 53%).
Diarrhea, nausea, fatigue, vomiting, musculoskeletal pain, hepatotoxicity, renal impairment, dyspnea, edoema, decreased appetite, cough, pneumonia, disorientation, constipation, abdominal pain, and QTc interval prolongation were the most frequent side effects ( 20%). Reduced lymphocytes, increased aspartate aminotransferase, increased sodium, decreased sodium, decreased haemoglobin, increased creatinine, decreased albumin, increased alanine aminotransferase, increased lipase, decreased platelets, decreased magnesium, and decreased potassium were the most prevalent laboratory abnormalities ( 25%).
Adagrasib tablets should be taken orally twice day at a dose of 600 mg until the condition progresses or there is intolerable toxicity.
Dr. Nishant Mittal is a highly accomplished researcher with over 13 years of experience in the fields of cardiovascular biology and cancer research. His career is marked by significant contributions to stem cell biology, developmental biology, and innovative research techniques.
Research Highlights
Dr. Mittal's research has focused on several key areas:
1) Cardiovascular Development and Regeneration: He studied coronary vessel development and regeneration using zebrafish models1.
2) Cancer Biology: At Dartmouth College, he developed zebrafish models for studying tumor heterogeneity and clonal evolution in pancreatic cancer.
3) Developmental Biology: His doctoral work at Keio University involved identifying and characterizing medaka fish mutants with cardiovascular defects.
4) Stem Cell Research: He investigated the effects of folic acid on mouse embryonic stem cells and worked on cryopreservation techniques for hematopoietic stem cells.
Publications and Presentations
Dr. Mittal has authored several peer-reviewed publications in reputable journals such as Scientific Reports, Cardiovascular Research, and Disease Models & Mechanisms1. He has also presented his research at numerous international conferences, including the Stanford-Weill Cornell Cardiovascular Research Symposium and the Weinstein Cardiovascular Development Conference.
In summary, Dr. Nishant Mittal is a dedicated and accomplished researcher with a strong track record in cardiovascular and cancer biology, demonstrating expertise in various model systems and a commitment to advancing scientific knowledge through innovative research approaches.
