AACR Annual Meeting 2024: news roundup
Read the latest news highlights from the AACR 2024 Annual Meeting (5 –10 April 2024, CA, USA), providing insights into the latest advancements and discoveries in cancer research and treatment.
Two-pronged approach of SYNC-T yields promising results for prostate cancer subtype
A pilot study of a biologic drug-device, termed SYNC-T (in situ T Cell education and stimulation), yields positive results for metastatic castrate-resistant prostate cancer (mCRPC), a tumor type that traditionally has a poor response to immunotherapy.
First, a probe is used to freeze a section of the tumor, inducing oncolysis and the release of neoantigens. Immediately after oncolysis, the researchers introduced a drug termed SV-102. At the AACR Annual Meeting, the team presented data from the Phase I clinical trial of the SYNC-T, involving 15 individuals with mCRPC.
“SV-102 simultaneously blocks two distinct mechanisms of immune suppression and activates two distinct mechanisms of immune enhancement, allowing the vaccine-induced T cells to activate and mount a systemic antitumor immune response,” explained study author Charles Link (Lankenau Institute for Medical Research, PN, USA and Syncromune, FL, USA).
Among the 13 evaluable patients, 11 exhibited an objective response, with five complete responses and six partial responses reported. The remaining two evaluable patients had stable disease when data analysis was conducted. Six patients reported mild to moderate treatment-related adverse events.
“Our results indicate that SYNC-T is associated with a high response rate without generating severe toxicity in this initial group of patients, which opens up opportunities to expand the role of immunotherapy in mCRPC. Further, this approach uses standard procedures already employed by urologists and radiologists, which means the treatment could potentially be rapidly adopted by treating physicians,” Link added.
Have drugs granted US FDA accelerated approval lived up to their expectations?
A cohort study has revealed that fewer than half of the 46 cancer drugs granted FDA accelerated approval from 2013–2017 demonstrated clinical benefit in confirmatory trials after 5+ years of follow-up.
Between 2013–2023, 129 drugs were granted accelerated approval in the US. In this study, the researchers evaluated the efficacy and quality of life improvements of these drugs post-approval, a previously unexplored aspect. Of the 46 drugs that had reached the 5-year mark, 41% did not improve overall survival or quality of life in their confirmatory trials.
The team also uncovered notable changes to FDA processes, with a shift towards longer timeframes for conversion to regular approval (1.6 to 3.6 years) and shorter times for drug withdrawal (9.9 to 3.6 years).
“Faster, appropriate withdrawal decisions are a good thing for patients, as they ensure that ineffective drugs are on the market for a shorter period of time,” explained study author Ian TT Liu (Brigham and Women’s Hospital and Harvard Medical School, MA, USA).
“We hope these findings will encourage greater communication between patients and physicians about the uncertainty surrounding cancer drugs approved on preliminary surrogate measures and the potential risks and benefits of a given treatment,” Liu added.
Read about the latest FDA drug approvals here.
PETRA trial highlights the potential of selective PARP inhibitors
A Phase I/II trial termed PETRA, which evaluated the PARP1-specific inhibitor saruparib in several cancer types, has demonstrated promising objective response rates and progression-free survival outcomes for certain breast cancer patients.
All of the PARP inhibitors that are currently approved by the US FDA block both PARP1 and PARP2. “When we were developing first-generation PARP inhibitors, we weren’t able to increase the doses above a certain threshold because of toxicity. By designing selective PARP1 inhibitors, we have a great opportunity to improve safety, tolerability, pharmacokinetics, pharmacodynamics, efficacy, and combinability with other therapies,” commented Timothy Yapp (The University of Texas MD Anderson Cancer Center, TX, USA), who presented the findings at AACR 2024.
The PETRA trial evaluated saruparib across several tumor types, homologous recombination repair (HRR)-deficient breast, ovarian, pancreatic and prostate cancer, among the 31 breast cancer patients enrolled in the trial, the objective response rate was 48.4%, median duration of response was 7.3 months and median progression-free survival was 9.1 months. Further details regarding the safety profile of this drug across the patient cohort can be found here.