Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2015 Nov;171(4):463-70.
doi: 10.1111/bjh.13603. Epub 2015 Jul 27.

Phase II study of an AKT inhibitor MK2206 in patients with relapsed or refractory lymphoma

Yasuhiro Oki  1 , Michelle Fanale  1 , Jorge Romaguera  1 , Luis Fayad  1 , Nathan Fowler  1 , Amanda Copeland  1 , Felipe Samaniego  1 , Larry W Kwak  1 , Sattva Neelapu  1 , Michael Wang  1 , Lei Feng  2 , Anas Younes  1
Affiliations
Clinical Trial

Phase II study of an AKT inhibitor MK2206 in patients with relapsed or refractory lymphoma

Yasuhiro Oki et al. Br J Haematol. 2015 Nov.

Abstract

We conducted a phase II study of the AKT inhibitor, MK2206 in patients with relapsed or refractory lymphoma of any histology excluding Burkitt lymphoma or lymphoblastic lymphoma. MK-2206 was administered orally at 200 mg once weekly in 28-d cycles up to 12 cycles in the absence of progression or significant toxicity. The dose was adjusted based on tolerance. A total of 59 patients were enrolled. The final doses patients received were 300 mg (n = 33), 250 mg (n = 2), 200 mg (n = 16) and 135 mg (n = 8). Based on intent-to-treat analysis, objective response was observed in 8 (14%) patients (2 complete response and 6 partial response), with median response duration of 5·8 months. The overall response rate was 20% in 25 patients with classical Hodgkin lymphoma. Rash was the most common toxicity (any grade 53%, Grade 3 in 15%) and was observed in a dose-dependent manner. The correlative cytokine analysis showed paradoxical increase in several cytokines, which may be explained by negative feedback mechanism induced by the on-target effect of AKT inhibitor. Our data demonstrate that MK2206 has a favourable safety profile with a modest activity in patients with relapsed Hodgkin lymphoma. The future studies should explore mechanism-based combinations (clinicaltrials.gov NCT01258998).

Keywords: AKT; clinical trials; lymphoma; target therapy.

PubMed Disclaimer

Conflict of interest statement

statements Authors disclosed no conflict of interest.

Figures

Fig 1
Fig 1
The waterfall chart showing the changes of tumour size. The figure shows 54 patients. Five patients that did not undergo formal tumour measurement after treatment. *Indicates complete metabolic response defined by fluorodeoxyglucose-positron emission tomography scan. HL, Hodgkin lymphoma; DLBCL, diffuse large B-cell lymphoma; MCL, mantle cell lymphoma; AITL, angioimmunoblastic T-cell lymphoma.
Fig 2
Fig 2
Progression free survival. The curves are for classical Hodgkin lymphoma (cHL, n = 25), diffuse large B-cell lymphoma (DLBCL, n = 11) and mantle cell lymphoma (MCL, n = 7). Other subtypes had <5 patients in each cohort and thus, the curves were not generated for them.
Fig 3
Fig 3
Changes in cytokine levels during therapy.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Bertacchini J, Guida M, Accordi B, Mediani L, Martelli AM, Barozzi P, Petricoin E, 3rd, Liotta L, Milani G, Giordan M, Luppi M, Forghieri F, De Pol A, Cocco L, Basso G, Marmiroli S. Feedbacks and adaptive capabilities of the PI3K/Akt/mTOR axis in acute myeloid leukemia revealed by pathway selective inhibition and phosphoproteome analysis. Leukemia. 2014;28:2197–2205. - PubMed
    1. Biondo A, Yap TA, Yan L, Patnaik A, Fearen I, Baird RD, Papadopoulos KP, Delgado LM, Taylor A, Lupinacci L, Blackman SC, Decordova S, Tall M, Heaton S, Garrett MD, Sullivan D, Bono JSD, Tolcher AW. Phase I clinical trial of an allosteric AKT inhibitor, MK-2206, using a once weekly (QW) dose regimen in patients with advanced solid tumors. Journal of Clinical Oncology. 2011;29 abstr 3037. - PubMed
    1. Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V. Revised response criteria for malignant lymphoma. Journal of Clinical Oncology. 2007;25:579–586. - PubMed
    1. Dreyling M, Morschhauser F, Bron D, Bouabdallah K, Vitolo U, Linton K, Van Den Neste E, Mappa S, Giurescu M, Childs BH, Zinzani PL. Preliminary results of a phase II study of single agent Bay 80-6946, a novel PI3K inhibitor, in patients with relapsed/refractory, indolent or aggressive lymphoma. Blood. 2013;122 abstr 87.
    1. Engelman JA. Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nature Reviews Cancer. 2009;9:550–562. - PubMed

Publication types

MeSH terms

Associated data