CD40 agonist primes T-cell response to treat pancreatic cancer, early trial results show
Immune checkpoint inhibition has revolutionized cancer treatment, but not all patients and tumors respond. Priming T cells by stimulating CD40 shows promise in treating pancreatic cancer.
“CD40 activation is a promising pathway to pursue clinically, especially for patients with pancreatic and other cancers that are immune to checkpoint therapy,” said Katelyn T. Byrne, PhD, Perelman School of Medicine Abramson Cancer Center, University of Pennsylvania. “Agonistic CD40 is a reasonable partner for combination treatment.”
Byrne opened the Clinical Trials Plenary Session Immuno-oncology and Cell Therapy Trials on Saturday, April 10, with results from a phase Ib trial of the agonistic CD40 antibody selicrelumab in neoadjuvant treatment of resectable pancreatic ductal adenocarcinoma. Registrants can watch a replay of this clinical trials plenary anytime until June 21, 2021.
Sixteen patients were enrolled at four sites before surgery. Patients in one arm received selicrelumab alone, and those in a second arm received a combination of selicrelumab plus gemcitabine/nab-paclitaxel. The median survival for all 16 patients was 23.4 months, median disease free survival 13.8 months, and eight patients were alive a median of 20 months after surgery. The one-year survival rate was 81.8 percent for arm I and 100 percent for arm II.
Second interim analysis confirms pembrolizumab effective for metastatic cutaneous SCC
A preplanned second analysis of the global KEYNOTE-629 study of pembrolizumab confirms that the agent is a viable treatment for locally advanced (LA) and recurrent or metastatic (R/M) cutaneous squamous cell carcinoma (cSCC). Initial results showed an objective response rate of 24.4 percent for R/M cSCC after a medium follow-up of 11.4 months.
Brett G.M. Hughes, MSci, MBBS, Royal Brisbane and Women’s Hospital and University of Queensland, reported efficacy and safety data for the LA cohort at 13.4 months follow-up and the RM cohort at 23.8 months.
The objective response rate was 50 percent for the LA cohort and 35.2 percent for the R/M cohort. Neither cohort has yet reached the median duration of response.
“Most responses were quite deep and significant, and the treatment was relatively well-tolerated by this elderly population,” Hughes said. “These data establish pembrolizumab as a treatment option for cSCC.”
CD19/CD20 CAR-T promising treatment for lymphoma
Results from a first-in-human anti-CD19/CD20 bispecific CAR-T trial showed positive results treating multiple lymphomas. Five lymphoma patients who had failed multiple lines of prior therapy were treated in a phase I dose-escalation trial.
Infusions were well-tolerated, reported Sanaz N. Ghafouri, MD, University of California, Los Angeles.
Three patients in a lower-dose arm and the only patient in the higher-dose arm had a complete response. Four of the five patients had ongoing complete remission after a median follow-up of 13 months. Median duration of response, progression-free survival, and overall survival have not yet been reached.
“Early results demonstrate exceptional safety and promising clinical efficacy,” Ghafouri said. “Further analysis with more patients and longer follow-up is needed.”
Longer follow-up confirms autologous TIL success in advanced melanoma
A 28-month analysis of the Iovance C-144-01 trial of an autologous tumor infiltrating lymphocyte (TIL) therapy, lifileucel, confirms initial positive reports from patients with unresectable or metastatic melanoma that has progressed on checkpoint inhibitors. The phase II multicenter study of 66 patients used cryopreserved TIL product expanded from autologous tumors, manufactured at a central facility, and infused back into patients.
All 66 patients reported at least one treatment-emergent adverse event. Event profiles were consistent with underlying advanced disease and the safety profile of IL-2 administered after lifileucel.
The objective response rate was 36.4 percent, and the median duration of response had not been reached at a median of 28.1 months.
“Responses are ongoing,” said Jason Alan Chesney, MD, PhD, James Graham Brown Cancer Center, University of Louisville. “Lifileucel has demonstrated efficacy and durability of response. It represents a viable therapeutic option that warrants further investigation in patients with metastatic melanoma.”
Safety and efficacy of atezolizumab-bevacizumab combination in high-risk HCC population matches broad trial results
Initial results of the IMbrave 150 trial found that the combination of atezolizumab (atezo) + bevacizumab (bev) is more effective than sorafenib (sor) in unresectable HCC. An additional 12 months of follow-up showed similar results, with a median overall survival (OS) of 19.2 months for atezo + bev vs. 13.4 months for sor and hazard ratio of 0.66 for combination therapy.
An analysis of patients with high-risk found similar results, with a median OS of 7.6 months for combination therapy versus 5.5 months for sor and a hazard ratio of 0.62. Adverse events were similar in high-risk and non-high-risk patients.
“The risk-benefit assessment remains in favor of atezo + bev regardless of patient risk status,” said
Richard S. Finn, MD, Jonsson Comprehensive Cancer Center and the Geffen School of Medicine at the University of California, Los Angeles. “The combination is standard of care for previously untreated, unresectable hepatocellular carcinoma.”