PURPOSE TAPUR is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. The results of a cohort of patients with colorectal cancer (CRC) with BRAF mutations treated with cobimetinib (C) plus vemurafenib (V) are reported. METHODS Eligible patients had advanced CRC, no standard treatment options, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, tumors with BRAF V600E/D/K/R mutations, and no MAP2K1/2, MEK1/2, or NRAS mutations. C was taken 60 mg orally once daily for 21 days followed by seven days off, and V was taken 960 mg orally twice daily. Simon's two-stage design was used with a primary study end point of objective response or stable disease of at least 16 weeks duration. Secondary end points were progression-free survival, overall survival, and safety. RESULTS Thirty patients were enrolled from August 2016 to August 2018; all had CRC with a BRAF V600E mutation except one patient with a BRAF K601E mutation. Three patients were not evaluable for efficacy. Eight patients with partial responses and six patients with stable disease of at least 16 weeks duration were observed for disease control and objective response rates of 52% (95% CI, 35 to 65) and 30% (95% CI, 14 to 50), respectively. The null hypothesis of 15% disease control rate was rejected ( P < .0001). Thirteen patients had at least one grade 3 adverse event or serious adverse event at least possibly related to C + V: anemia, decreased lymphocytes, dyspnea, diarrhea, elevated liver enzymes, fatigue, hypercalcemia, hypophosphatemia, rash, photosensitivity, and upper gastrointestinal hemorrhage. CONCLUSION The combination of C + V has antitumor activity in heavily pretreated patients with CRC with BRAF mutations.

<p>Changes in peripheral GITR+ effector memory T-cells from baseline were measured in the 25 mg, 75 mg, 250 mg, and 500 mg cohorts.</p>

<p>Supplementary Table 1. Characteristics of patients with prolonged SD ({greater than or equal to}24 weeks)</p>

<p>Patients receiving MEDI1873 at doses ranging from 7.5-25 mg or 75-250 mg were assessed for changes in the soluble factors interferon gamma (IFNy), IFNy-induced protein 10 (IP-10), interferon-inducible T cell alpha chemoattractant(I-TAC), and monokine induced by IFNy (MIG).</p>

<p>Visits after Day 57 were excluded for visual purposes. The excluded visits were: Days 71, 85, 99, 127, 155, 183, 211, 239, 267, 295, 323 and 351.</p>