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Table 1 Phase I/II clinical trials of some Akt inhibitors

From: Targeting Akt in cancer for precision therapy

Trial ID Official title Akt inhibitor Combination Cancer type Phase Efficacy Grade  3 adverse effects Ref
NCT01042379 ISPY-2 MK-2206 Neoadjuvant chemotherapy Breast cancer II Estimated pCR: 61.8% with MK-2206 versus 35% with control for hormone receptor-negative/HER2-positive breast cancer Rash: 22.6% (MK-2206) versus 0 (control);
Hyperglycemia: 4.3% (MK-2206) versus 0 (control)
[181]
NCT02162719 LOTUS Ipatasertib Paclitaxel Metastatic TNBC II Median PFS: 6.2 m with ipatasertib versus 4.9 m with placebo;
Median PFS in the PIK3CA/AKT/PTEN-altered population: 9.0 m with ipatasertib versus 4.9 m with placebo;
Median PFS in the PIK3CA/AKT/PTEN-non-altered population: 5.3 m with ipatasertib versus 3.7 m with placebo;
Median OS: 23.1 m with ipatasertib versus 16.2 m with placebo in the PIK3CA/AKT/PTEN-altered population
Rash: 2% (ipatasertib) versus 0 (placebo);
Neutropenia: 10% (ipatasertib) versus 2% (placebo)
[183]
NCT02301988 FAIRLANE Ipatasertib Paclitaxel Stage I-IIIa TNBC II pCR: 17% with ipatasertib versus 13% with placebo in the overall population; 16% with ipatasertib versus 13% (placebo) in the PTEN-low population; 18% with ipatasertib versus 12% (placebo) in the PIK3CA/AKT/PTEN-altered population;
rCR: 39% with ipatasertib versus 9% (placebo) in the PIK3CA/AKT/PTEN-altered population
Diarrhea: 17% versus 1%Hyperglycemia: 0 versus 0;
Rash: 1% versus 1%
[194]
NCT01485861 N.A Ipatasertib Abiraterone Metastatic castration- resistant prostate cancer II rPFS: 8.31 m with ipatasertib (200 mg) versus 6.37 m with placebo in molecularly unstratified population; Median OS: 21.5 m with ipatasertib (200 mg) versus 15.64 m with placebo;
rPFS:11.1 m with ipatasertib (200 mg) versus 4.6 m with placebo in PTEN-loss population; 4.6 m with ipatasertib (200 mg) versus 5.6 m with placebo in PTEN-non-loss population
Diarrhea: 14.3% (400 mg ipatasetib), 3.4% (200 mg ipatasertib) versus 1.2% (placebo);
Asthenia: 7.2% (400 mg ipatasetib), 1.1% (200 mg ipatasertib) versus 1.2% (placebo)
[195]
NCT01625286 BEECH Capivasertib Paclitaxel ER +/HER metastatic breast cancer II PFS: 10.9 m with capivasertib versus 8.4 m with placebo in the overall population;
PFS: 10.9 m with capivasertib versus 10.8 m with placebo in the PIK3CA-mutated population
Diarrhea: 22% with capivasertib versus 2% with placebo;
Hyperglycemia:13% with capivasertib versus 0% with placebo;
Maculopapular rash: 9% with capivasertib versus 0% with placebo
[186]
NCT01992952 FAKTION Capivasertib Fulvestrant Aromatase inhibitor-resistant, advanced ER+/HER2 breast cancer II PFS: 10.3 m with capivasertib plus fulvestrant versus 4.8 m with placebo plus fulvestrant in the overall population;
Objective response: 29% in capivasertib group versus 8% in placebo group;
CBR: 55% in capivasertib group versus 41% in placebo group;
PFS: 10.3 m with capivasertib plus fulvestrant versus 4.8 m with placebo plus fulvestrant in the PI3K/PTEN pathway-nonaltered population;
PFS: 9.5 m with capivasertib plus fulvestrant versus 5.2 m with placebo plus fulvestrant in the PI3K/PTEN pathway-altered population;
OS: 30.5 m with capivasertib plus fulvestrant versus 18.7 m with placebo plus fulvestrant in the PI3K/PTEN pathway-altered population;
23.7 m with capivasertib plus fulvestrant versus 20.3 m with placebo plus fulvestrant in the PI3K/PTEN pathway-nonaltered population
Hypertension: 32% in capivasertib group versus 24% in placebo group
Diarrhea: 14% in capivasertib group versus 4% in placebo group;
Rash: 20% in capivasertib group versus 0 in placebo group;
Infection: 6% in capivasertib group versus 3% in placebo group
[187]
NCT02423603 PAKT Capivasertib Paclitaxel Untreated metastatic TNBC II PFS: 5.9 m with capivasertib plus paclitaxel versus 4.2 m with placebo plus paclitaxel in the overall population;
PFS: 9.3 m with capivasertib plus paclitaxel versus 3.7 m with placebo plus paclitaxel in the PIK3CA/AKT1/PTEN-altered population;
PFS: 5.3 m with capivasertib plus paclitaxel versus 4.4 m with placebo plus paclitaxel in the PIK3CA/AKT1/PTEN-nonaltered population;
OS: 19.1 m with capivasertib plus paclitaxel versus 12.6 m with placebo plus paclitaxel in the overall population;
Median duration of response: 13.3 m with capivasertib plus paclitaxel versus 3.5 m with placebo plus paclitaxel in the PIK3CA/AKT1/PTEN-altered population
Diarrhea: 13% (capivasertib) versus 1% (placebo);
Rash: 4% (capivasertib) versus 0% (placebo)
Infection: 4% (capivasertib) versus 0% (placebo)
Hyperglycemia: 1.5% with capivasertib versus 0% with placebo
[191]
NCT01226316 N.A Capivasertib None Akt1 E17K mutant tumors II Median PFS: 5.5 m in ER+ breast cancer patients; 6.6 m in gyneologic cancer papatients; 4.2 m in other cancer patients Hyperglycemia: 24%; diarrhea: 17%; rash: 15.5% Discontinuation rate: 12% [199]
NCT01226316 N.A Capivasertib Fulvestrant Akt1 E17K mutant/ER+ metastatic breast cancer I Combination therapy: ORR, 36%; CBR24, 50% in fulvestrant-pretreated patients; ORR, 20%; CBR24, 47% in fulvestrant-naïve patients.
Capivasertib monotherapy: ORR, 20%
Hyperglycemia: 30%;
Rash: 20%
[201]
NCT00700882 NCI-MATCH
(EAY131-Y)
Capivasertib None Akt1 E17K mutated metastatic tumor II ORR: 28.6%; CR: 1/35; PR: 9/35; Median duration of response: 4.4 m; SD: 46%; PD: 2/35; Median PFS: 5.5 m; Overall 6-month PFS: 50%; Median OS: 14.5 m Hyperglycemia: 26%;
Maculopapular rash: 11%
[200]
NCT02299648 VICTORY Capivasertib Paclitaxel PIK3CA-mutated/amplified gastric cancer N.A ORR: 33.3% (8/24);
50% in PIK3CA E542K mutant population,
18.8% in the non-E542K cohort
  [202]
  1. CBR: clinical benefit rate; CR: complete response; ORR: objective response rate; OS: overall survival; pCR: pathologic complete response; PFS: progression-free survival; rPFS: radiographic progression-free survival; SD: stable disease; N.A.: not available