01 Aug Laminar Pharma closes patient recruitment in its first clinical study with 2OHOA in cancer
Laminar Pharma announces the closure of patient recruitment in its first clinical study with 2OHOA (MIN-001-1203), a Phase I/IIa open label, non-randomized, safety, pharmacokinetics, pharmacodynamics and preliminary efficacy study of 2OHOA in adult patients with advanced solid tumors including malignant glioma. Five centres have participated in the study, three in Spain and two in the UK.
Palma de Mallorca (Spain), August 1st 2016 –
54 patients with advanced solid tumours have participated in the Phase I/IIa clinical study with 2OHOA, half of them with malignant glioma. Results show an excellent safety profile, with no drug-related relevant toxicity effects associated with the investigational product reported, even at doses well above the expected therapeutic range. Very encouraging clinical activity has been observed in nine patients with refractory advanced solid tumours, six of them with malignant glioma.
The study comprised two parts: 1) a dose-escalation phase where 32 patients have been treated with different doses and in which the Maximum Tolerated Dose (MTD) was defined as 12 g/day (4 g three times daily) and 2) an expanded safety part with two cohorts, one with malignant glioma patients (n=12) and another with other advanced solid tumors (n=10), in both cases treated at the MTD (12 g/day).
7 cohorts were completed in the dose escalation phase, with doses ranging from 0.5 g/day to 16 g/day. 32 patients (15 of them 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 two or three 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 (8 g twice daily) dose, experiencing frequent gastrointestinal effects that in some cases were difficult to manage. No drug-related serious adverse events 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). In the safety expansion phase, 22 patients have been treated with the MTD (12 g/day, 4g three times daily) in two cohorts, 18 of them being eligible for safety assessment. The results of these two expansion cohorts re-confirm the excellent safety profile of 2OHOA, with no drug-related relevant adverse effects reported.
Overall the 54 patients have received 2OHOA treatment for more than 125 months (182 cycles), 46 of them being eligible for the safety assessment. 22 patients have been dosed with 2OHOA at the Maximum Tolerated Dose (12 g/day) over a total period of more than 63 months (>90 cycles), confirming an excellent safety and tolerability profile.
Promising anti-cancer activity of 2OHOA as single agent has been confirmed in several patients with advanced refractory solid tumours. Five patients in the dose escalation part and four in the expanded safety phase have shown objective clinical benefit according to RANO (for glioma) or RECIST (for other solid tumors) criteria. 6 patients with refractory malignant glioma have experienced clinical benefit, including one GBM patient that has had a marked shrinkage (-93% over baseline) of the target lesion for almost 3 years. Other four refractory malignant glioma patients have shown stable disease (SD) for at least 6 months, two of them still ongoing with SD in cycles 11 (7 months) and 10 (6 months) respectively. All available data of the study is currently being evaluated and the patient samples collected for biomarker and genetic evaluation are being analyzed at different labs in order to complete the official report of the clinical study.
The positive results of this first MIN-001-1203 trial warrants further clinical development of 2OHOA and Laminar Pharma is now planning a next Phase IIb study in order to evaluate the therapeutic potential and safety of this product in combination with the Standard of Care (SoC, radiotherapy plus Temozolomide), compared with the SoC alone, in subjects with newly-diagnosed malignant glioma. If results of the Phase IIb study are positive, Laminar Pharma will seek conditional approval as a first line treatment, in combination with current SoC) for glioblastoma in Europe.