2021 Pipeline Updates: Examining Ongoing Clinical Research With Potential in Prostate Cancer

Over the course of 2021, breakthroughs in clinical research within the prostate cancer space abounded. Clinical trials assessing everything from promising novel targets, investigational radiopharmaceuticals, and even innovative diagnostics agents with uptake in prostate-specific membrane antigen (PSMA) account for some of the many measures that have been taken in order to push the needle forward for the treatment of prostate cancer. In the third and final part of our series examining promising innovations coming down the oncology pipeline, CancerNetwork® examines the most recent updates on these clinical trials, highlighting what may be looked to going forward to in the coming year and beyond.

Don’t forget to read part 1 of the series, featuring potential innovations in the lung cancer space, as well as part 2, which features ongoing clinical trials in breast cancer.

Novel Anti–B7-H3 ADCs Take the Spotlight in Prostate Cancer

B7-H3 protein may prove to be a promising novel target for treatment with immunotherapy in prostate cancer.¹ In fact, data on 2 B7-H3 inhibitors read out at the 2021 European Society for Medical Oncology Congress.

B7-H3 is highly expressed in a number of solid tumor malignancies such as prostate cancer, non–small cell lung cancer, breast cancer, head and neck cancer, melanoma, and squamous cell carcinoma of the head and neck. Investigators believe that it may impact immune suppression, as well as tumor-autonomous roles leading to cancer growth. Additionally, B7-H3 appears to be expressed in the epithelium, tumor-associated vascular endothelium, and stroma. In a multicohort phase 1 expansion cohort trial (NCT03729596), 93% of patients with metastatic castration-resistant prostate cancer (mCRPC) had a B7-H3 H-score of 160 or higher.

Investigators evaluated the safety and antitumor activity of antibody-drug conjugate MGC018 in a population of patients with mCRPC (n = 40).² Patients within the mCRPC cohort had a best overall response rate of 25%, including 2 confirmed partial responses (PRs) and 2 unconfirmed PRs. Those within this cohort also had a mean B7-H3 H-score of 236. Ten of 16 patients in the mCRPC cohort experienced a reduction in target lesions from baseline

Thirty-nine patients within the cohort were evaluable for prostate-specific antigen (PSA) response. Among these patients, 53.8% had reductions in PSA from baseline of 50% or greater. Additionally, 61.5% of patients continued to receive treatment.

The second phase 2 trial (NCT02923180) evaluated the anti–B7-H3 antibody enoblituzumab in patients with localized prostate cancer.3 Investigators enrolled 32 patients, 12% of whom experienced grade 3/4 adverse effects (AEs). Thirty-four percent of patients experienced pre-prostatectomy declines of over 10%. One year following surgery, 66% of patients had a PSA of 0. Additionally, the median time to PSA recurrence had not been reached (95% CI, 9.4–not evaluable).

“Virtually every prostate cancer cell expresses some degree of B7-H3, which appears to be associated with rapid recurrence and earlier metastasis,” Eugene Shenderov, MD, PhD, an assistant professor of oncology at Johns Hopkins Medicine and lead author of both studies, said in a press release. He continued, “Everything seems to point to the fact that B7-H3 is potentially an important therapeutic target in the prostate cancer setting.”

Phase 3 Clinical Research Kicking Off for 177Lu-PSMA-I&T

Curium recently received a Study May Proceed letter from the FDA in October 2021 regarding its investigational therapeutic radiopharmaceutical product 177Lu-PSMA-I&T, allowing them to advance with the phase 3 ECLIPSE trial assessing the product in patients with mCRPC.⁴ The organization is working hand-in-hand with several sites in the United States in order to initiate the multicenter, open-label randomized trial which will compare the efficacy of 177Lu-PSMA-I&T with hormone therapy in this patient population. The radiopharmaceutical works by binding to the PSMA protein.

“We are excited about advancing Lu 177 PSMA I&T to the clinical trial stage, particularly in light of our recent announcement for our Cu 64 PSMA I&T imaging agent.We believe this represents an exciting opportunity for patients nationwide and their healthcare providers,” Mike Patterson, chief executive officer at Curium, North America, said in a press release.

Curium noted that they expect to manufacture 177Lu-PSMA-I&T in a facility in Noblesville, Indiana, which will allow them to leverage centralized production capabilities and logistical expertise.

“We are committed to working closely with the FDA to potentially bring this new therapeutic radiopharmaceutical agent to patients and their healthcare professionals,” Ed Porter, vice president of Medical and Compliance at Curium, explained.“We look forward to engaging additional clinical trial sites as we finalize our clinical development program.”

PROPELLER Trial Examining 64Cu SAR-bisPSMA Hits Recruiting Halfway Mark

A total of 15 of 30 patients have been enrolled on the phase 1 PROPELLER trial (NCT04839367), which seeks to assess the diagnostic value of 64Cu SAR-bisPSMA in those with untreated and confirmed prostate cancer who are scheduled to undergo radical prostatectomy.⁵

“We are excited to have quickly and successfully recruited half of the patients planned for the PROPELLER trial with all 3 sites actively recruiting and imaging prostate cancer patients across Australia. We have been able to not only generate strong preliminary clinical data since the trial commencement in July 2021, but also validate our on-demand distribution model where the 64Cu-SAR-bisPSMA has been shipped to the trial sites across Australia from a central manufacturing facility with minimal delays or interruptions,” Alan Taylor, PhD, executive chairperson at Clarity Pharmaceuticals, said in a press release.

The multicenter, blinded review, dose-ranging, non-randomized PET imaging trial will administer 64Cu-SAR-bisPSMA to patients prior to undergoing surgery. The study has 4 particular goals:

1. Identify safe and tolerability of 64Cu SAR-bisPSMA
2. Assess different dose levels
3. Identify ability of 64Cu SAR-bisPSMA to detect primary disease
4. Assess ability of 64Cu SAR-bisPSMA to detect primary disease vs 68Ga PSMA-11

The trial will enroll patients who are 18 years or older with a life expectancy of more than 3 months. Patients are also required to have confirmed disease via histopathology with plans to receive radical prostatectomy. Adequate renal function is also required.

“The preliminary data from the patients imaged in the PROPELLER trial to date look very promising as it supports the evidence of higher uptake of 64Cu SAR-bisPSMA in the tumours that has been shown in the pre-clinical studies. Higher uptake in the tumours means that they are more visible on the PET scans and hence have a higher chance of being detected. These initial results are encouraging for further development of this product as a diagnostic, and the higher uptake and retention also make it an exciting therapeutic target with 67Cu,” Louise Emmett, MD, FAANMS, FRACP, a clinical research leader in advanced prostate cancer, assistant professor, and director of theranostics and nuclear medicine at Garvan Institute of Medical Research, concluded.

References

1. Studies find B7-H3 protein a novel, promising target for prostate cancer treatments. News release. John Hopkins Medicine. November 2, 2021. Accessed December 9 ,2021. https://bit.ly/3pLqxD2
2. Shenderov E, Mallesara G, Wysocki P, et al. MGC018, an anti-B7-H3 antibody-drug conjugate (ADC), in patients with advanced solid tumors: preliminary results of phase 1 cohort expansion. Ann Oncol. 2021;32(suppl 5):S626-S677. doi:10.1016/annonc/annonc702
3. Shenderov E, Mallesara GHG, Wysocki P, et al. MGC018, an anti-B7-H3 antibody-drug conjugate (ADC), in patients with advanced solid tumors: preliminary results of phase I cohort expansion. Ann Oncol. 2021;32(suppl 5): 626-S677. doi:10.1016/annonc/annonc702
4. Curium initiates ECLIPSE, a phase 3 clinical trial for its investigational Lu 177 PSMA I&T. News release. Curium. October 27, 2021. Accessed December 13, 2021. https://bit.ly/31XFjP5
5. Fifty percent recruitment milestone for PROPELLER prostate cancer trial. News release. Clarity Pharmaceuticals. December 1, 2021. Accessed December 13, 2021. https://prn.to/31Up4lV