On January 18, 2022 Seagen Inc. (Nasdaq:SGEN) reported data from a phase 1 clinical trial combining SEA-CD40 with chemotherapy and an anti-PD-1 in patients with metastatic PDAC at the ASCO (Free ASCO Whitepaper) GI annual meeting taking place in San Francisco, January 20 – 22, 2022 (Press release, Seagen, JAN 18, 2022, View Source [SID1234605552]). SEA-CD40 is a novel, investigational, nonfucosylated monoclonal receptor-agonistic antibody directed to CD40, which is expressed on antigen-presenting cells. In preclinical models, the combination of SEA-CD40 and chemotherapy resulted in antitumor activity which is further enhanced with anti-PD-1 treatment.

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In the ongoing phase 1 trial, SEA-CD40 was combined with chemotherapy [gemcitabine and nab-paclitaxel (GnP)], and an anti-PD-1 (pembrolizumab), in 61 patients with untreated metastatic PDAC. Of these, 40 patients received 10 mcg/kg and 21 patients received 30 mcg/kg of SEA-CD40. Key endpoints include confirmed objective response rate (cORR) per RECIST v1.1 by investigator, progression-free survival (PFS) and overall survival (OS).

Activity of SEA-CD40 in combination with GnP and pembrolizumab was observed in both doses of SEA-CD40 tested. The overall (N = 61) cORR was 44 percent, median PFS was 7.4 months (95 percent CI: 5.6-9.0), and median OS was 15.0 months (95 percent CI: 7.8-19.9).

Follow-up for efficacy is ongoing.

The regimen demonstrated a manageable and tolerable safety profile. Overall, ≥ grade 3 treatment-emergent adverse events (TEAEs) were fatigue, nausea, neutropenia, infusion-related reaction, chills, diarrhea, and pyrexia.

This combination also showed evidence of immune activation consistent with the SEA-CD40 mechanism of action.

"Preliminary activity is encouraging based on historical chemotherapy outcomes. Further survival follow up is required to inform our next steps in pancreatic cancer," said Roger Dansey, M.D., Chief Medical Officer at Seagen. "We are continuing to advance the ongoing phase 2 trial of SEA-CD40 in melanoma and in non-small cell lung cancer."

The abstract published at the ASCO (Free ASCO Whitepaper) GI meeting can be found here.

Details of Seagen Presentation at ASCO (Free ASCO Whitepaper) GI:

Abstract Title

Abstract #

Presentation

Presenter

Preliminary Results of a Phase 1 Study of SEA-CD40, Gemcitabine, Nab-Paclitaxel, and Pembrolizumab in Patients with Metastatic Pancreatic Ductal Adenocarcinoma (PDAC).

#TPS451

January 21, 2022

12:05 PST

Poster Session B: Pancreas, Small Bowel, and Hepatobiliary Tract

David Bajor, M.D.

Case Western Reserve University

More information about the SEA-CD40 phase 1 clinical trial, including enrolling centers, is available by visiting www.clinicaltrials.gov.

About Sugar-Engineered Antibody (SEA) Technology

Seagen’s proprietary SEAs are monoclonal antibodies engineered to lack fucose, a sugar molecule that can limit the potential of therapeutic antibodies to engage an anticancer immune response. Enhanced binding to effector cells results in better crosslinking and activation of CD40 signaling in immune cells. Preclinical data indicate SEAs have the potential to work alone and in combination with a broad range of anticancer therapies. The clinical activity and safety of SEAs are currently under investigation.