BPX-601 and BPX-603 Trials Discontinued in Advanced Solid Tumors

Bellicum Pharmaceuticals has discontinued 2 phase 1/2 trials (NCT02744287; NCT04650451) evaluating the safety and preliminary efficacy of the GoCAR T-cell products BPX-601 and BPX-603 in combination with rimiducid in heavily pretreated patients with advanced solid tumors following an assessment of the risk/benefit profile of the combination of BPX-601 and rimiducid.¹

Per the release, the last patient treated in the phase 1/2 trial evaluating BPX-601, who had metastatic castration-resistant prostate cancer (mCRPC), experienced serious immune-mediated adverse effects (AEs) including grade 4 cytokine release syndrome (CRS), representing the second dose-limiting toxicity (DLT) in this dose-escalation cohort.

As a result, the company temporarily halted enrollment in its trials and conducted a thorough review of the risk/benefit profile of the regimen, revealing clinically meaningful efficacy, including a prostate specific antigen (PSA) 50 response in 5 of 9 patients, 4 of whom also achieved a PSA90 response.

However, the company determined it does not have the proper resources to optimize the dose and schedule of BPX-601 cells and the activating agent rimiducid, or the design of the BPX-601 cell construct to amend the risk/benefit profile of the regimen. As such, the company will relay the decision with clinical trial sites and regulatory agencies, and an evaluation of the company’s strategic alternatives will take place.

BPX-601 CAR T cells are genetically engineered to express a CAR to target the prostate stem cell antigen and a rimiducid-inducible signaling domain, which functions as a molecular go-switch to enhance activation and proliferation.²

The trial evaluating BPX-601 enrolled patients with select advanced solid tumors, including mCRPC. In dose escalation, patients received an intravenous (IV) infusion of BPX-601 followed by one or more IV infusions of rimiducid. Dose escalation of BPX-601 was continued until the recommended cell dose level was reached. In dose expansion, patients received an IV infusion of BPX-601 at the recommended cell dose level followed by one or more IV infusions of rimiducid.

The single-arm study evaluating BPX-603 enrolled previously treated patients with locally advanced or metastatic HER2-positive solid tumors.³ Eligible patients received one dose of BPX-603 on day 1, followed by an IV infusion of rimiducid weekly, as tolerated, starting on day 8 and continued until treatment discontinuation criteria were met.

In the first patients treated in this trial at dose level 1 of 0.1 x 10⁶ cells/kg of BPX-603 alone or followed by weekly rimiducid, no DLTs occurred despite occurrences of serious AEs, including pleural effusion and pneumonia.⁴ Other grade 3 or greater treatment-emergent AEs included neutropenia, leukopenia, and anemia. No CRS or immune effector cell–associated neurotoxicity syndrome events were reported. In terms of efficacy, modest cell engraftment and expansion occurred. Patients were subsequently enrolled into dose level 2, which evaluated 1 x 10⁶ cells/kg alone or followed by weekly rimiducid.

In October 2020, the company announced positive interim data from the dose-escalation trial with BPX-601 in patients with relapsed/refractory metastatic pancreatic cancer.⁵ Results showed signals of rimiducid-mediated CAR T-cell activation, although clinically meaningful activity measured by RECIST v1.1 criteria was not observed. At that time, the company announced that it would begin to enroll patients with mCRPC before the year’s end and reevaluate the pancreatic cohort after completion of the safety cohort.

In December 2021, the company announced positive interim data in the mCRPC population treated with BPX-601, evidenced by a confirmed partial response.4 Additionally, in the first three-patient cohort of patients with mCRPC treated at 5 x 10⁶ cells/kg of BPX-601 followed by a single dose of rimiducid, no DLTs were observed. AEs were similar to those previously seen with BPX-601 and rimiducid in metastatic pancreatic cancer and in line with other cellular therapy regimens.

References

1. Bellicum discontinues phase 1/2 trials and initiates evaluation of strategic alternatives. News release. Bellicum Pharmaceuticals. March 14, 2023. Accessed March 15, 2023. https://ir.bellicum.com/news-releases/news-release-details/2023
2. Safety and activity study of PSCA-targeted CAR-T cells (BPX-601) in subjects with selected advanced solid tumors. ClinicalTrials.gov. Updated August 12, 2022. Accessed March 15, 2023. https://clinicaltrials.gov/ct2/show/NCT02744287
3. Safety and activity study of HER2-targeted dual switch CAR-T cells (BPX-603) in subjects with HER2-positive solid tumors. ClinicalTrials.gov. Updated August 12, 2022. Accessed March 15, 2023. https://clinicaltrials.gov/ct2/show/NCT04650451
4. Bellicum announces positive interim data from phase 1/2 GoCAR-T® studies, secures $35 million private placement equity financing priced at market. News release. December 6, 2021. Bellicum Pharmaceuticals. Accessed March 15, 2023. https://ir.bellicum.com/news-releases/news-release-details/2021
5. Bellicum announces interim BPX-601 data and corporate restructuring. News release. Bellicum Pharmaceuticals. October 29, 2020. Accessed March 15, 2023. https://ir.bellicum.com/news-releases/news-release-details/2020