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S3. t-SLCO1B3 expression was optimized using various concentrations of chetomin at different timepoints in (A) LNCaP and (B) 22Rv1 cell lines.

Supplemental Figure Legends 1-4

Supplemental Table 1

S4. Both (A) lt-SLCO1B3 and (B) ct-SLCO1B3 were plotted as a function of t-SLCO1B3 in 384 tissue and tumor samples.

S1. Expression of (A) doxycycline-inducible GFP-linked OATP1B3 was confirmed in the membrane and not cytosolic fractions of PC3 cells using a GFP-specific antibody Abcam goat antibody (#ab6673).

S2. Ten hypoxia response elements were identified by sequence alignment of the RefSeq SLCO1B3 gene (NG_032071.1).

The FDA approved capmatinib and tepotinib on May 6, 2020, and February 3, 2021, respectively. Capmatinib is indicated for patients with metastatic non–small cell lung cancer (mNSCLC) whose tumors have a mutation leading to mesenchymal–epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test. Tepotinib is indicated for mNSCLC harboring MET exon 14 skipping alterations. The approvals were based on trials GEOMETRY mono-1 (capmatinib) and VISION (tepotinib). In GEOMETRY mono-1, overall response rate (ORR) per Blinded Independent Review Committee (BIRC) was 68% [95% confidence interval (CI), 48–84] with median duration of response (DoR) 12.6 months (95% CI, 5.5–25.3) in 28 treatment-naïve patients and 41% (95% CI: 29, 53) with median DoR 9.7 months (95% CI, 5.5–13) in 69 previously treated patients with NSCLC with mutations leading to MET exon 14 skipping. In VISION, ORR per BIRC was 43% (95% CI: 32, 56) with median DoR 10.8 months (95% CI, 6.9–not estimable) in 69 treatment-naïve patients and 43% (95% CI, 33–55) with median DoR 11.1 months (95% CI, 9.5–18.5) in 83 previously-treated patients with NSCLC harboring MET exon 14 alterations. These are the first two therapies to be FDA approved specifically for patients with metastatic NSCLC with MET exon 14 skipping.

On September 15, 2021, the FDA granted accelerated approval to mobocertinib (Exkivity, Takeda Pharmaceuticals USA, Inc.) for the treatment of adult patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy. The approval was based on data from Study AP32788–15–101 (NCT02716116), an international, non-randomized, multi-cohort clinical trial that included patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. The overall response rate in 114 patients whose disease had progressed on or after platinum-based chemotherapy was 28% [95% confidence interval (CI), 20%–37%] with a median duration of response of 17.5 months (95% CI, 7.4–20.3). The most common adverse reactions (>20%) were diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain. Product labeling includes a Boxed Warning for QTc prolongation and torsades de pointes. This is the first approval of an oral targeted therapy for patients with advanced EGFR exon 20 insertion mutation–positive NSCLC.

On August 16, 2018, the U.S. Food and Drug Administration approved lenvatinib (Lenvima, Eisai Inc.) for first-line treatment of patients with unresectable hepatocellular carcinoma (HCC). Approval was based on an international, multicenter, randomized, open-label, noninferiority trial (REFLECT; NCT01761266) conducted in 954 patients with previously untreated metastatic or unresectable HCC. Patients were randomized (1:1) to receive lenvatinib (12 mg orally once daily for patients with a baseline body weight ≥60 kg and 8 mg orally once daily for patients with a baseline body weight Implications for Practice This article describes the U.S. Food and Drug Administration's review of data from a single trial, REFLECT, that supported the approval of lenvatinib, as a single agent, for the first-line treatment of unresectable hepatocellular carcinoma (HCC). REFLECT was an open-label, noninferiority trial that randomized 954 patients with HCC who were ineligible for liver-directed therapy with no prior systemic therapy for HCC to lenvatinib or sorafenib. REFLECT demonstrated that lenvatinib-treated patients had similar survival, more responses, and longer time to progression than those receiving sorafenib. Serious side effects were more common among lenvatinib-treated patients. Lenvatinib is an effective treatment for patients with previously untreated HCC.