31st May 2020 –VAXIMM Announces First Results from Phase I/II Trial in Progressive
Glioblastoma with Oral T-cell Immunotherapy VXM01 in Combination with PD-L1
Inhibitor Avelumab to be Presented at ASCO2020 Conference, which is summarized
as follows：
The safety run-in results from a Phase I/II study in progressive
glioblastoma with its lead product candidate, oral VXM01, in combination with
the PD-L1 inhibitor avelumab are being presented as an oral presentation at the
2020 American Society of Clinical Oncology (ASCO) Virtual Meeting being held
May 29-31, 2020. The trial is part of a collaboration with Merck KGaA,
Darmstadt, Germany and Pfizer Inc.
Background: VEGFR2 overexpression in
glioblastoma serves as a target for VEGFR2 primed T cells using VXM01 DNA
vaccine encoding for VEGFR2. VXM01 is delivered in a bacterial Ty21a carrier
suitable for oral administration. A previous phase I/II study in 14 patients
with progressive glioblastoma showed that detection of VEGFR2 specific T cells
as well as altered intra-tumoral immunity is correlated with prolonged overall
survival, one partial response was reported with VXM01 alone. Three patients
received nivolumab in addition to VXM01, which resulted in one complete and one
partial clinical response. Based on these findings, a trial combining VXM01 and
avelumab was designed.
Methods:A multicentre, open-label phase I/II study
(EudraCT 2017-003076-31) in progressive glioblastoma includes 30 patients
(24 non-resectable, 6 resectable) previously treated with
temozolomide/radiotherapy. VXM01 is administered on day 1, 3, 5, 7 followed by
boostings q4w. Avelumab 800mg is given intravenously q2w. Treatment continues
up to week 48 followed by a 2 year observation period. The safety run-in phase
of dose groups treated with VXM01 106 or 107 CFU
plus avelumab was completed with 9 patients. Safety evaluation by the Data
Safety Monitoring Board was performed after 3 and 9 patients treated for at
least 5 weeks. Endpoints include safety and tolerability, objective response
rate (ORR), clinical response using immune-response assessment in Neurooncology
criteria (iRANO), and immunological assays like ELISpot, FACS, TCR-sequencing
and tumor stainings.
Results: No treatment-related toxicities were observed. Three
partial responses with tumor reductions of 58, 81 and 95% to baseline were
reported in 9 patients. Two of these patients are progression-free > 6
months. Significant VEGFR2 specific T cell responses were measured in several
patients, and pre-existing intra-tumoral T cells are positively associated with
the effectiveness of the immunotherapy combination.
Conclusions: VXM01 in combination with avelumab was safe and
produces detectable peripheral VEGFR-2 specific immune responses. Three patients
had an objective response.
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