A phase I/II clinical trial is underway evaluating intravenous Oncoprex in combination with Tarceva® (erlotinib) in stage IIIB/IV lung cancer patients without an activating EGFR mutation and in patients with an activating EGFR mutation whose cancer has progressed on erlotinib therapy. Patients without the EGFR mutation represent the vast majority of lung cancer patients. However, such patients are generally not candidates for Tarceva therapy.
The Phase I portion of the trial was a dose escalation study seeking primarily to establish the safety profile of the combination of TUSC2 and erlotinib and to establish a Maximum Tolerated Dose (MTD) to be delivered to patients in the Phase II portion of trial. Inclusion criteria of the ongoing Phase II trial consist of adult patients who had either failed or are not candidates for TKI and showed disease progression.
In the Phase II Combination Trial, subjects receive Oncoprex in combination with erlotinib every 21 days until the occurrence of progressive disease (PD), unacceptable toxicity, withdrawal of consent, or study treatment discontinuation for other reasons, whichever occurs first. We believe that the results from the ongoing Phase II trial to date are encouraging. Out of 10 patients, 9 had received 2 or more cycles and were therefore evaluable for response. Four patients had tumor regression. The median duration of response is 3 months. The disease control rate (CR+PR+SD > 8weeks) was 78%, which substantially exceeds the 7% response rate (with no CRs) and 58% disease control rate reported for the LUX-Lung 1 trial, a clinical trial of afatinib in a comparable group of patients.
One patient in the Phase II combination trial had a Complete Response, or CR, under the Response Evaluation Criteria in Solid Tumors, or RECIST. This patient, a 58 year old female, upon enrollment in the study had metastatic NSCLC status following 6 cycles of pemetrexed and carboplatin and 2 cycles of maintenance pemetrexed with cancer progression. The patient’s tumor has EGFR exon 18 and 20 missense mutations, which are not sensitive to erlotinib. This patient had disappearance of both the lung primary tumor and the lung, liver, and lymph node metastases.
Tarceva® is a registered trademark of Astellas and the Roche Group of companies.