MGA012 at SITC (so far, just the dose escalation phase data):
>>A phase 1 study of the safety, tolerability, and pharmacokinetics (PK) of MGA012 (anti-PD-1 antibody) in patients with advanced solid tumors
Nehal Lakhani1, Janice M. Mehnert2, Drew Rasco3, Michael Gordon4, Joanna Lohr5, Pepi Pencheva5, Sharad Sharma5, Hua Li5, Ross LaMotte-Mohs5, Paul Moore5, Jichao Sun5, Bradley Sumrow5, Jon Wigginton5, John Powderly6
1START Midwest - South Texas Accelerated Research Therapeutics, LLC, Grand Rapids, MI, USA
2Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
3START - South Texas Accelerated Research Therapeutics, LLC, San Antonio, TX, USA
4Honor Health Research Institute, Scottsdale, AZ, USA
5MacroGenics, Inc., Rockville, MD, USA
6Carolina BioOncology Institute, Huntersville, NC, USA
Background
MGA012 is a humanized, IgG4? monoclonal antibody (mAb) that recognizes human programmed cell death protein 1 (PD-1). MGA012 binds to PD-1 expressing T cells, inhibits PD-1 and PD-L1/PD-L2 interactions, and disrupts the negative signaling axis to restore T cell function. The biological activity of MGA012 is comparable to replicas of approved anti-PD-1 mAbs when assessed in vitro, including blockade of PD-1 and PD-L1/PD-L2 interactions, inhibition of PD-1 signaling, and enhancement of T cell effector function.
Methods
This phase 1, dose escalation study will characterize the safety, tolerability, PK/PD, immunogenicity, and preliminary anti-tumor activity of MGA012 administered IV every two or four weeks in patients with advanced solid tumors. MGA012 has been evaluated in sequential dose escalation cohorts (1- 10 mg/kg) of 3 to 6 patients each, using a 3+3 design. Four tumor-specific expansion cohorts will be treated at the maximum tolerated dose of MGA012. Selective cohort expansion was allowed during escalation to gather further safety and PK/PD data.
Results
At the data cutoff, 33 patients (12M/21F, median age 63 years) with diverse tumor types were treated at doses from 1-10 mg/kg, including 21 patients on treatment at the time of data cutoff. MGA012 has demonstrated acceptable tolerability with no dose- limiting toxicities (DLTs). Treatment-related adverse events (AEs) occurred in 20/33 (61%) patients, most commonly fatigue (n=9) and nausea (n=5). Treatment-related Grade =3 AEs occurred in 3/33 (9%) patients and include increased lipase (n=2) and vaginal ulceration/inflammation (n=1). A single treatment-related serious adverse event (SAE) has been reported (aphasia occurring in conjunction with the emergence of new brain metastases). Immune-related AEs (irAEs) were limited to rash (n=3), infusion-related reaction (n=1), and vaginal ulceration/inflammation (n=1). MGA012 has PK features consistent with other IgG4 monoclonal antibodies, as well as full and sustained receptor occupancy at all dosing levels tested, consistent with its known binding characteristics. Twenty-two patients were response evaluable at the data cutoff. Three patients have experienced unconfirmed partial responses (including ovarian, MSI-high colorectal and uterine papillary serous carcinoma), and 4 additional patients experienced stable disease as a best response. Others had radiographic progressive disease or clinical progression.
Conclusions
MGA012 has demonstrated an acceptable safety profile, predictable PK/PD, and early evidence of anti-tumor activity. Subsequent to dose escalation, patients will be enrolled on tumor-specific monotherapy expansion cohorts. Future trials also are planned for combination testing of MGA012 with T cell directed, CD3-based DART® molecules.
Trial Registration
NCT03059823<<
snip
From the abstract just out. In the bio-Twitter-sphere, SITC in general seems be getting regarded as something of a bust, wrt to interpretable, market cap moving data.
Cheers, Tuck
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