Encouraging Anti-Tumor Activity for BXCL701 in mCRPC
On February 11, 2021, BioXcel Therapeutics, Inc. (NASDAQ:BTAI) presented updated data for the ongoing Phase 1b/2 clinical trial of BXCL701, the company’s oral innate immune system modulator, at the 2021 ASCO GU Cancers Symposium. The multicenter, open label trial is designed to determine the safety and efficacy of BXCL701 used in combination with pembrolizumab in patients with metastatic castration resistant prostate cancer (mCRPC) with either therapy-induced neuroendocrine (t-NEPC) or adenocarcinoma phenotype (NCT03910660). A schematic of the trial is shown below, with final efficacy results presented for patients with adenocarcinoma in the Phase 1b portion of the study and preliminary results presented for patients with adenocarcinoma in the Phase 2 portion of the study.
The following table shows the best response for patients in both the Phase 1b (n=7) and Phase 2 (n=15) portion of the study. For patients in the Phase 1b portion of the study, there was a disease control rate (DCR) of 100%, with one patient experiencing a partial response (PR) and another three patients experiencing stable disease (SD). In addition, one patient experienced a PSA50 response (50% reduction from peak PSA value). For the Phase 2 portion of the study, five of the patients were evaluable by RECIST 1.1 and there was a DCR of 80%. One patient experienced a PSA50 response and out of four evaluable patients for circulating tumor cells (CTC), 1 patient had a response (defined as conversion from ≥5/7.5 mL to <5/7.5 mL).
The following graph shows the best PSA response for patients in both the Phase 1b and Phase 2 portion of the trial. A total of 6/17 (35%) had any PSA response while 2/17 (12%) had a PSA70 response.
The poster presentation also highlighted a few of the best responders from the trial:
• PID 207: This patient had five prior systemic therapies (bicalutamide, abiraterone+prednisone, enzalutamide, sipuleucel, docetaxel+cabazitaxel). Thus far, they have received 16 cycles of BXCL701+pembrolizumab. The patient exhibited a PSA50 response by 6 weeks with a maximum reduction of 84% (baseline PSA = 163.1 ng/mL). The patient also exhibited a RECIST 1.1 PR by 12 weeks with a 35% reduction in target lesions and the disappearance of 2/5 non-target lymph nodes.
• PID 908: This patient had five prior systemic therapies (leuprolide, sipuleucel, enzalutamide, docetaxel, cabazitaxel). Thus far, they have received 5 cycles of BXCL701+pembrolizumab. A PSA50 response occurred at 3 weeks and is ongoing at 15 weeks (99% reduction; 25 ng/mL to 0.2 ng/mL). The patient also experienced a CTC conversion at 3 weeks. Lastly, the patient had a RECIST 1.1 minor response (19% reduction in target lesions) that is ongoing.
• PID 909: This patient had five prior systemic therapies (bicalutamide, leuprolide, enzalutamide, docetaxel, abiraterone+prednisone). Thus far, they have received 4 cycles of BXCL701+pembrolizumab. There was a 40% reduction in PSA (111.4 ng/mL to 66.9 ng/mL) at 12 weeks and a RECIST 1.1 minor response (27% reduction in target lesions) that is ongoing.
Regarding safety, the following table shows the reported adverse events that were judged by the investigator to be related to BXCL701. The majority of events were low grade and a number of them were consistent with cytokine activation. Grade 3 hypotension was seen in a patient during the first week of treatment, thus step up dosing was implemented for all new patients for the first week of treatment with 0.2 mg BXCL701 administered twice a day. Escalation to 0.3 mg twice a day was permitted if no treatment related adverse events Grade >1 or skipped doses due to hypotension or orthostasis occurred during the first week of treatment.
The Phase 1b/2 results for BXCL701 in combination with pembrolizumab for the treatment of advanced prostate cancer are encouraging, particularly the PSA responses seen in heavily pretreated patients who have few treatment options available. We look forward to additional updates from the trial later in the year. At this point the majority of the company’s value is based on the potential for BXCL501, however based on the Phase 1b/2 results we have increased the contribution of BXCL701 to our model, which has slightly increased our valuation to $145.
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