23 Nov Laminar Pharma initiates recruitment in expansion cohorts of clinical study with 2OHOA in cancer
Palma de Mallorca (Spain), November 23rd 2015 –
Laminar Pharma announced today that in the Dose Escalation TC held this morning with all the Clinical Investigators and the Medical Monitor of the MIN-001-1203 study with 2OHOA, it was agreed that the Maximum Tolerated Dose (MTD) in this study will be set as 12g per day (4g TDS, three times daily). As from today two additional safety expansion cohorts (one with 10 glioma patients and another with 10 patients with solid biopsiable tumours) will start recruiting participants at a dose of 12g/day (4g TDS) in order to evaluate the effect of 2OHOA in different biomarkers and to further explore preliminary efficacy in glioma patients.
The main primary objective of the MIN-001-1203 clinical study has already been achieved with the identification of the MTD. 2OHOA has proved to be safe and generally well tolerated up to 12g/day (4g three times daily), while at 16g/day (8g twice daily) frequent gastrointestinal effects occurred in most patients. No other toxicity effects related to the medication reported in any of the 32 patients treated with doses ranging from 0.5g to 16g per day. Promising clinical activity confirmed in 4 patients (3 with glioblastoma, GBM), including one GBM patient with a sustained tumour regression after 26 months of treatment.
7 cohorts of the MIN-001-1203 study have already been completed, with doses ranging from 500mg/day to 16g/day. 32 patients (12 with glioma) have been treated in these first 7 cohorts, 28 of which have completed at least one cycle of treatment and are evaluable for safety assessment. 2OHOA, administered as an oral suspension 2 or 3 times daily, has been generally well tolerated up to 12 g/day, while patients have had difficulties to handle the large volume of medication required for the 16g/day (8g twice daily) dose, experiencing frequent gastrointestinal effects that in some cases were difficult to manage. Nodrug-related serious adverse events (SAE), or other relevant toxicity effects associated to the investigational product have been reported in any of the 32 patients treated, other than the tolerability issues experienced at the highest dose levels (gastrointestinal effects). The pharmacokinetic (PK) profile was dose-proportional with no accumulation up to 4g/day and no food interactions were observed. At doses up to 4g/day the t1/2 ranged from 1,5 to 3,8h, while at 12 gr/day t1/2 was 9,4h. Accumulation was observed at doses of 8g/day and higher.
Even though this is safety study which does not contemplate patient selection criteria with a view of exploring efficacy (particularly in the dose escalation part just completed) relevant clinical activity has been reported in 4 patients, 3 of them with GBM, including one GBM patient (ongoing) that has achieved a sustained partial response (PR) on RANO criteria (tumour shrinkage >91%) lasting now for more than 26 months. Two other GBM patients have had Stable Disease (SD) for 6 months and a fourth patient with progressive mesothelioma had SD lasting for 10 months.
MIN-001-1203 is a Phase I/IIA, open label, non-randomized, safety, pharmacokinetics, pharmacodynamics and efficacy study of 2OHOA for adult patients with advanced solid tumors including malignant glioma. The study will be performed in two phases – a dose escalation phase following a standard “3+3” design to establish dose-limiting toxicity (DLT) and a safe dose of 2OHOA followed by two expanded safety cohorts (10 malignant glioma and 10 other advanced solid tumours suitable for biopsy) treated at the maximum tolerated dose (MTD). If the MTD is well tolerated in the expanded safety cohorts, that dose becomes the recommended Phase 2 dose (RP2D)
Laminar Pharma is now opening a new fund-raising campaign in order to conduct a PIIb study with 2OHOA in GBM which, if successful, could lead to a conditional approval in Europe for the treatment of newly-diagnosed GBM in combination with radiotherapy and temozolomide.