2020 Gastrointestinal Cancers Symposium – January 23 - 25, 2020. Photo Courtesy © 2020 ASCO/Todd Buchanan.

The Targeted Agent and Profiling Utilization Registry or TAPUR Study, a non-randomized clinical trial that aims to describe the performance (both safety and efficacy) of U.S. Food and Drug Administration (FDA)-approved, targeted anticancer drugs prescribed for treatment of patients with advanced cancer that has a potentially actionable genomic alteration, shows positive results for the potential benefit of various molecularly targeted drugs in patients with advanced colorectal cancer.

ASCOThe new data were presented at the 2020 Gastrointestinal Cancers Symposium, taking place January 23-25, 2020 at the Moscone West Building in San Francisco, California.

Cobimetinib plus vemurafenib
Results in a cohort of heavily pre-treated patients with advanced colorectal cancer with a BRAF V600E mutation treated with a combination of cobimetinib (Cotellic™), a MEK inhibitor developed by Exelixis and Genentech, in combination with vemurafenib (Zelboraf®), an inhibitor of the B-Raf enzyme developed by Plexxikon and Genentech, demonstrated strong anti-tumor activity. [1]

Eligible patients participating in this study, which took place from August 2016 to August 2018, had advanced colorectal cancer, without standard treatment options and measurable disease, ECOG PS 0-2, and adequate organ function.

As part of patients evaluation, genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. These results confirmed that patients had BRAF V600E/D/K/R mutation and no MAP2K1/2, MEK1/2, NRAS mutations. A total of 30 patients enrolled. Two patients were not evaluable for efficacy.

The results of the study showed that the combination of cobimetinib + vemurafenib showed anti-tumor activity in heavily pre-treated CRC pts with BRAF V600E mutations. Further study is warranted to confirm the efficacy of cobimetinib + vemurafenib in this population.

Pertuzumab plus trastuzumab
A second study investigated pertuzumab + trastuzumab. Between November 2016 to September 2018 this study enrolled 28 patients with ERBB2 amplification. One patients also had an ERBB2 mutation.[2]

After the initial dosing, the recommended dosing for pertuzumab was 420 mg IV over 30-60 mins every 3 weeks and trastuzumab 6 mg/kg over 30-60 mins every 3 weeks.

A total of 79% of patients had at least 3 prior treatments. The researchers observed four patients with partial response (PR) and 10 patients with stable disease at 16+ weeks per RECIST (SD16+) for DC and OR rates of 50% (90% CI, 36% to 60%) and 14% (95% CI, 4% to 33%), respectively.

Two patients had at least one grade 3 adverse events possibly related to treatment of pertuzumab + trastuzumab including anemia, infusion reaction, and left ventricular dysfunction.

In their analysis, the researchers found that the  combination of pertuzumab + trastuzumab showed anti-tumor activity in heavily pre-treated colorectal cancer patients with ERBB2 amplification. Additional analyses by RAS mutation status are pending. Based on these results, the researchers believe that further study in this patient population is warranted to confirm efficacy of pertuzumab + trastuzumab. [2]

Pertuzumab in high tumor mutational burden
In a study investigating monotherapy pertuzumab, twenty-eight patients with high tumor mutational burden enrolled from June 2017 to November 2018. High tumor mutational burden was defined as ≥9 mutations/megabase (Muts/Mb) by a FoundationOne test (n=26) or other tests (n=2) approved by the Molecular Tumor Board. [3]

The researchers found that monotherapy with pertuzumab demonstrated anti-tumor activity in heavily pre-treated colorectal cancer patients with high tumor mutational burden. They concluded that, based on these results, additional study is warranted to confirm the efficacy of pertuzumab in this patients population.

Clinical trial
Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer (TAPUR) – NCT02693535

Reference
[1] Klute K, Garrett-Mayer E, Halabi S, Mangat PK, Nazemzadeh R, Yost KJ, Butler NL, Perla V, et al. Cobimetinib plus vemurafenib (C+V) in patients (Pts) with colorectal cancer (CRC) with BRAF V600E mutations: Results from the TAPUR Study. J Clin Oncol 38, 2020 (suppl 4; abstr 122)
[2] Gupta R, Garrett-Mayer E, Halabi S, Mangat PK, D’Andre SD, Meiri E, Shrestha S, Warren SL, Ranasinghe S., et al. Pertuzumab plus trastuzumab (P+T) in patients (Pts) with colorectal cancer (CRC) with ERBB2 amplification or overexpression: Results from the TAPUR Study. J Clin Oncol 38, 2020 (suppl 4; abstr 132)
[3] Meiri E, Garrett-Mayer E, Halabi S, Mangat PK, Shrestha S, Ahn ER, Osayameh O, Perla V, Schilsky RL. Pembrolizumab (P) in patients (Pts) with colorectal cancer (CRC) with high tumor mutational burden (HTMB): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study. J Clin Oncol 38, 2020 (suppl 4; abstr 133)

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