Table 2.

Key Recent US Food and Drug Administration Approvals for Precision Oncology Targeted Therapies

THERAPY NAME (APPROVAL DATE)	REFERENCES	MECHANISM OF ACTION	INDICATION	APPROVAL TYPE	CLINICAL TRIAL EVIDENCE	SUMMARY OF TRIAL EVIDENCE
Pembrolizumab (March 2017)	FDA 2017,47 Marcus 2019,48 Le 201549	PD‐1 inhibitor	Adult and pediatric patients with unresectable or metastatic solid tumors with MSI‐H or dMMR	Accelerated approval based on tumor response rate and duration	KEYNOTE‐016 (NCT01876511), KEYNOTE‐164 (NCT02460198), KEYNOTE‐158 (NCT02628067), KEYNOTE‐012 (NCT01848834), and KEYNOTE‐028 (NCT02054806)	Approval based on a pooled analysis of 5 single‐arm trials
Larotrectinib (November 2018)	FDA 2018,50 Chen & Chi 2019,51 Drilon 201852	TRK inhibitor	Adult and pediatric patients with unresectable or metastatic solid tumors with neurotropic TRK fusion	Accelerated approval based on tumor response rate and duration	LOXO‐TRK‐14001 (NCT02122913), NAVIGATE (NCT02576431), and SCOUT (NCT02637687)	Approval based on a pooled analysis of 3 single‐arm trials
Entrectinib (August 2019)a	FDA 2019,53 Demetri 201854	TKI inhibitor	Adult and pediatric patients with unresectable or metastatic solid tumors with neurotropic TRK fusion without treatment options	Accelerated approval based on tumor response rate and duration	ALKA‐372‐001 (EudraCT 2012‐000148‐88), STARTRK‐1 (NCT02097810), and STARTRK‐2 (NCT02568267)	Approval based on a pooled analysis of 3 single‐arm trials
Vemurafenib (November 2017)b	FDA 2017,55 Hyman 2015,56 Diamond 201857	BRAF enzyme inhibitor	Erdheim‐Chester disease with BRAF V600 mutation	Regular approval	VE‐Basket (NCT01524978)	Approval based on “other solid tumor” cohort of a multicohort phase 2 basket trial

Abbreviations: ALKA‐372‐001, phase 1/2 entrectinib trial; EudraCT, European Union Drug Regulating Authorities Clinical Trials Database; FDA, US Food and Drug Administration; dMMR, deficient mismatch repair; KEYNOTE‐012, Study of Pembrolizumab (MK‐3475) in Participants With Advanced Solid Tumors; KEYNOTE‐016, Study of MK‐3475 in Patients With Microsatellite Unstable (MSI) Tumors (Cohorts A, B, and C); KEYNOTE‐028, Study of Pembrolizumab (MK‐3475) in Participants With Advanced Solid Tumors; KEYNOTE‐158, Study of Pembrolizumab (MK‐3475) in Participants With Advanced Solid Tumors; KEYNOTE‐164, Study of Pembrolizumab (MK‐3475) as Monotherapy in Participants With Previously Treated Locally Advanced Unresectable or Metastatic Colorectal Cancer; LOXO‐TRK‐14001, A Study to Test the Safety of the Investigational Drug Larotrectinib in Adults That May Treat Cancer; MSI‐H, microsatellite instability‐high; NAVIGATE, A Study to Test the Effect of the Drug Larotrectinib in Adults and Children With NTRK‐fusion Positive Solid Tumors; NCT, National Clinical Trials (clinicaltrials.gov identifier); PD‐1, programmed cell death protein 1; SCOUT, A Study to Test the Safety and Efficacy of the Drug Larotrectinib for the Treatment of Tumors With NTRK‐fusion in Children; STARTRK‐1, A Study of Oral RXDX‐101 in Adult Patients With Locally Advanced or Metastatic Cancer Targeting NTRK1, NTRK2, NTRK3, ROS1, or ALK Molecular Alterations; STARTRK‐2, Basket Trial of Entrectinib (RXDX‐101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions); TKI, tyrosine kinase inhibitor; TRK, tropomyosin kinase receptor; VE‐Basket, A Study of Vemurafenib in Participants With BRAF V600 Mutation‐Positive Cancers.

^aEntrectinib was also approved for an indication of adults with metastatic non–small‐cell lung cancer with receptor tyrosine kinase 1 (ROS1) positivity.

^bVemurafenib was approved in August 2011 for the treatment of unresectable or metastatic melanoma patients with BRAF V600E mutation (see Kim 201458).