CDX-1140 Demonstrates Clinical and Biological Activity in Patients with Advanced Solid Tumors in Phase 1 Dose Escalation Study
-Recommended and maximum tolerated dose defined as 1.5 mg/kg for further study-
-Expansion cohort in head and neck squamous cell carcinoma added based on observed clinical activity-
-Clinical trial collaboration with
CDX-1140 is currently in a Phase 1 dose escalation study. The study includes both monotherapy and combination cohorts with CDX-301, Celldex’s dendritic cell growth factor, designed to increase the number of dendritic cells which are critical to initiating antitumor immunity and are a key target for CDX-1140. Celldex intends to add additional combination cohorts with mechanisms that the Company believes could be complementary or synergistic with CDX-1140 and has prioritized a combination with KEYTRUDA® (pembrolizumab).
“CDX-1140 has exceeded the hurdles we defined for Phase 1 monotherapy development and has potential to be a best in class CD40 agonist,” said
“At 1.5 mg/kg, CDX-1140 has achieved one of the highest systemic dose levels in the CD40 agonist class and is associated with manageable immune-related adverse events that are consistent with approved, effective therapies like checkpoint inhibitors,” said
Promising clinical activity emerging with CDX-1140 monotherapy and combination with CDX-301 (n=38 patients with pre- and post-scans; n=7 patients awaiting assessment; enrollment ongoing). Patients were heavily pretreated (median of 4 prior therapies) and per protocol were required to have received all standard of care treatments prior to study entry.
- Two patients with radiographic evidence of tumor necrosis among 5 patients with recurrent/refractory HNSCC, including prior checkpoint inhibition therapy, treated with CDX-1140 monotherapy doses of 0.72mg/kg or higher
- Patient one: dramatic shrinkage of a large, protruding neck mass on physical exam after two doses of CDX-1140 at 1.5 mg/kg, evidence of tumor necrosis/cavitation on CT scan, patient reported decreased tumor pain
- Patient two: cavitation of greater than 50% of lung metastases on CT scan after one dose of CDX-1140 at 3 mg/kg
- A patient with gastroesophageal carcinoma with RECIST response after two cycles of CDX-1140 at 0.36 mg/kg plus CDX-301
- 41% shrinkage of liver and lymph node target lesions, including near complete resolution of the liver lesion
- Response duration of four months
- Six patients with stable disease: n=4 CDX-1140 monotherapy; n=2 CDX-1140/CDX-301 combination; duration 1.8 months to 5.4 months; one patient with immune unconfirmed progressive disease (iUPD) noted on first scan who has since continued treatment without confirmation of progressive disease for 10+ months at CDX-1140 at 0.09 mg/kg plus CDX-301
CDX-1140 monotherapy and combination with CDX-301 has been generally well tolerated to date
- CDX-1140 monotherapy dose escalation completed to 3.0 mg/kg, with maximum tolerated dose and recommended Phase 2 dose determined to be 1.5 mg/kg
- Mostly grade 1 or grade 2 drug related adverse events
- Mostly low grade, transient changes in serum liver transaminases
- 2 of 6 patients with pneumonitis at CDX-1140 3.0 mg/kg exceeding MTD
- No dose limiting toxicities to date in the CDX-301 combination cohorts up to 0.72 mg/kg CDX-1140; CDX-1140 at 1.5 mg/kg plus CDX-301 cohort currently ongoing
Potent pharmacological effects associated with immune activation observed
- Transient induction of inflammatory cytokines and chemokines associated with dendritic cell and T cell activation at higher dose levels
- Similar activation observed with each cycle of therapy
- Peripheral blood immune cells have upregulated immune activation markers
- CDX-301 markedly increases the number of dendritic cells and is associated with higher IL-12p40 induction; IL-12 is a key molecule for inducing anti-tumor T cell responses
Based on the clinical activity observed in HNSCC, Celldex is actively enrolling up to an additional 15 patients with HNSCC at 1.5 mg/kg CDX-1140 monotherapy. Dose escalation of CDX-1140 in combination with CDX-301 is nearing completion with patients currently enrolling to the 1.5 mg/kg CDX-1140 cohort. In addition, Celldex has amended the ongoing Phase 1 study to evaluate CDX-1140 in combination with KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy under a clinical trial collaboration agreement with
KEYTRUDA® is a registered trademark of
Celldex is developing targeted therapeutics to address devastating diseases for which available treatments are inadequate. Our pipeline includes immunotherapies and other targeted biologics derived from a broad set of complementary technologies which have the ability to engage the human immune system and/or directly inhibit tumors to treat specific types of cancer or other diseases. Visit www.celldex.com.
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Senior Vice President, Corporate Affairs & Administration
Source: Celldex Therapeutics, Inc.