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pembrolizumab alone (n=153) vs. Standard of Care (SoC) (n=154)
randomized controlled trial
Pembrolizumab
pembrolizumab at a dose of 200 mg every 3 weeks intravenously
chemotherapy FOLFIRI or FOLFOX plus targeted therapy
SOC (FOLFIRI or FOLFOX) with or without bevacizumab or cetuximab. All the chemotherapy regimens were repeated every 2 weeks. mFOLFOX6 (5-FU, oxaliplatin, and leucovorin)only, 41.6% received mFOLFOX6 plus bevacizumab, 3.2% received mFOLFOX6 plus cetuximab, 10.1% received FOLFIRI (5-FU, irinotecan, and leucovorin) alone, 36 received FOLFIRI plus bevacizumab, and 11 received FOLFIRI plus cetuximab.
Subjects randomized to the chemotherapy arm will have the option to crossover and receive treatment with pembrolizumab
mCRC - 1st line (L1)
open design
192 sites in 23 countries
P3/two sided and two interim analysis. hierarchical and splitting testing strategy : If PFS hypothesis is rejected, the alpha will be shifted to ORR and OS with equal split (1.25% one sided each)
this study demonstrated an improvement of PFS at the first analysis. OS results are not published yet.
atezolizumab alone (n=90) vs. regorafenib (n=90)
randomized controlled trial
atezolizumab monotherapy
atezolizumab monotherapy (1200 mg intravenously every 3 weeks. Atezolizumab dosemodification was not permitted.
regorafenib
regorafenib (160 mg orally once daily for days 1-21 of a 28-day cycle)
No crossover was allowed per protocol.
mCRC - 2nd line (L2)
Enrolment of patients with RAS wild-type tumours was capped at 50%
open label
73 academic medical centres and community oncology practices in 11 countries
P3/two sided no interim analysis . Two-sided type I error rate of 0·05 controlled by a hierarchical statistical testing procedure OS then PFS then ORR (testing atezolizumab monotherapy only if atezolizumab plus cobimetinib was positive).
IMblaze370 did not meet its primary endpoint of improved overall survival with atezolizumab plus cobimetinib or atezolizumab versus regorafenib.
atezolizumab plus cometinib (n=183) vs. regorafenib (n=90)
randomized controlled trial
atezolizumab plus cometinib
atezolizumab monotherapy (840 mg every 2 weeks) plus cobimetinib (60 mg orally once daily for days 1–21 of a 28-day cycle). Atezolizumab dose modification was not permitted. Cobimetinib dose modification was permitted and dose reduction for adverse events was allowed
regorafenib
regorafenib (160 mg orally once daily for days 1-21 of a 28-day cycle) Regorafenib dose modifications were allowed on the basis of local prescribing guidelines.
No crossover was allowed per protocol.
mCRC - 2nd line (L2)
Enrolment of patients with RAS wild-type tumours was capped at 50%.
open label
73 academic medical centres and community oncology practices in 11 countries
P3/two sided no interim analysis. Two-sided type I error rate of 0·05 controlled by a hierarchical statistical testing procedure OS then PFS then ORR (testing atezolizumab monotherapy only if atezolizumab plus cobimetinib was positive).
IMblaze370 did not meet its primary endpoint of improved overall survival with atezolizumab plus cobimetinib or atezolizumab versus regorafenib.
durvalumab plus tremelimumab (n=119) vs. BSC (n=61)
randomized controlled trial
durvalumab plus tremelimumab and BSC
75 mg of tremelimumab intravenously every 4 weeks for the initial 4 cycles only, durvalumab 1500 mg of intravenously every 4 weeks and BSC
BSC
No crossover was allowed between treatment groups
mCRC - 2nd line (L2)
Received a prior thymidylate synthase inhibitor (e.g. 5-fluorouracil (5-FU), capecitabine, raltitrexed, UFT) for metastatic disease or as adjuvant therapy.
open label
27 cancer centers across Canada
P2/ two sided (10%) No interim analysis. No specific statistic plan for secondary endpoint, but treshold at 10%
This phase 2 study suggests that combined immune checkpoint inhibition with durvalumab plus tremelimumab may be associated with prolonged OS in patients with advanced refractory CRC
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