CDX-1140

Shows activity

Also known as:

CDX 1140

Cancer types include:

breast cancer melanoma ovarian cancer sarcoma squamous cell carcinoma of the skin

HealthScout AI Analysis

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Overview

CDX-1140 (Celldex Therapeutics) is an investigational, fully human agonist monoclonal antibody targeting CD40. It has been evaluated in a first‑in‑human, phase 1 study (CDX1140‑01; NCT03329950) as monotherapy and in combinations (with FLT3L/CDX‑301, pembrolizumab, or chemotherapy). A randomized phase 2 trial in recurrent ovarian cancer is ongoing combining pembrolizumab + bevacizumab with or without CDX‑1140 (NCT05231122). (cdek.pharmacy.purdue.edu)

Mechanism of action

Target: CD40 on antigen‑presenting cells (dendritic cells, macrophages, B cells) and some tumor cells. CDX‑1140 is an IgG2 agonist that can activate CD40 signaling with minimal Fcγ‑receptor cross‑linking requirements and does not block CD40L, potentially allowing cooperative signaling. Preclinical studies show activation of dendritic and B cells and direct antitumor effects in CD40‑positive lymphoma and certain epithelial models. (aacrjournals.org)

Efficacy

Monotherapy and CDX‑301 combination (early phase 1 signals): Conference updates reported tumor shrinkage/necrosis signals in head and neck squamous cell carcinoma (HNSCC) and a complete response in one follicular lymphoma patient receiving CDX‑1140 + CDX‑301. These are uncontrolled, early findings. (ir.celldex.com)
Pembrolizumab combination (anti‑PD‑1/PD‑L1–refractory solid tumors): At SITC 2022, an expansion cohort of the phase 1 trial reported, among 6 evaluable HNSCC patients, 1 ongoing complete response (~16 months at report) and 1 case of stable disease; among 5 evaluable NSCLC patients, 4 had stable disease (up to 13 months). Detailed response rates across the full cohort were not reported. (onclive.com)

No peer‑reviewed, full‑length journal article reporting mature clinical outcomes was identified; available data derive from meeting abstracts, trial listings, and company scientific updates. (aacrjournals.org)

Safety

Dose finding: In phase 1, the recommended phase 2 dose (RP2D) for systemic dosing was established at 1.5 mg/kg IV. At 3.0 mg/kg, pneumonitis events occurred; most treatment‑related adverse events at or below the RP2D were grade 1–2 with transient liver enzyme elevations. Earlier interim data noted a dose‑limiting pneumonitis at 0.18 mg/kg during escalation; later updates reported generally manageable toxicity at doses up to the RP2D. (ir.celldex.com)
Combination with pembrolizumab: Described as generally well tolerated in the SITC 2022 expansion cohort report. Specific high‑grade immune‑related events were not detailed in the abstract summary. (onclive.com)

Ongoing/Planned studies

Phase 1 (completed): CDX1140‑01 (NCT03329950) included monotherapy and combinations (with CDX‑301, pembrolizumab, chemotherapy) to define MTD/RP2D and explore preliminary activity. (cdek.pharmacy.purdue.edu)
Phase 2 (recruiting): Randomized study in recurrent ovarian cancer testing pembrolizumab + bevacizumab with or without CDX‑1140 (NCT05231122). (cdek.pharmacy.purdue.edu)
In situ immunomodulation approach: A phase 1 trial (NCT04616248) is testing intratumoral CDX‑301/radiation plus CDX‑1140 and poly‑ICLC; trial-in-progress details were presented at ASCO 2024. (ascopubs.org)

Bottom line

CDX‑1140 is a differentiated CD40 agonist antibody with Fc‑independent agonism and non‑blocking of CD40L. Early clinical signals include a small number of objective responses (e.g., an ongoing CR in refractory HNSCC with pembrolizumab, and a CR in follicular lymphoma with CDX‑301), alongside disease stabilization in some patients. Safety has generally been manageable at the RP2D of 1.5 mg/kg, with pneumonitis emerging at higher doses. Robust, peer‑reviewed efficacy data (response rates, PFS/OS) have not yet been published. (aacrjournals.org)

Active trials using CDX-1140

Found 3 active trials using this drug:

Randomized Phase 2 Clinical Trial of Pembrolizumab Combined With Bevacizumab With or Without Agonist Anti-CD40 CDX-1140 in Patients With Recurrent Ovarian Cancer

Sponsor: Roswell Park Cancer Institute (other) Phase: 2 Start date: March 12, 2024

HealthScout AI summary: Adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer (serous/endometrioid/clear cell), platinum-sensitive or -resistant, ≤3 prior lines, measurable disease, and ECOG 0–1 are randomized to pembrolizumab plus bevacizumab with or without CDX-1140. CDX-1140 is an investigational agonist anti-CD40 antibody intended to activate dendritic/B cells and augment T-cell antitumor responses.

ClinicalTrials.gov ID: NCT05231122

A Phase I Study of In Situ Immunomodulation With CDX-301, Radiotherapy, CDX-1140, and Poly-ICLC in Patients With Unresectable and Metastatic Solid Tumors With Injectable Palpable Disease

Sponsor: University of Southern California (other) Phase: 1 Start date: Jan. 9, 2023

HealthScout AI summary: Adult patients with unresectable and metastatic melanoma, cutaneous SCC, BCC, Merkel cell carcinoma, high-grade sarcomas, or HER2-negative breast cancer with palpable, injectable lesions are eligible for this trial evaluating intratumoral CDX-301 (Flt3 ligand), radiotherapy, CDX-1140 (agonistic anti-CD40 antibody), and Poly-ICLC, with additional arms including pembrolizumab (PD-1 inhibitor) and tocilizumab (IL-6 receptor antagonist). The study focuses on safety and immunologic activity of this multi-agent in situ immunomodulation approach.

ClinicalTrials.gov ID: NCT04616248

Phase 1 Pilot Study With Dose Expansion of Chemotherapy in Combination With CD40 Agonist and Flt3 Ligand in Metastatic HER2 Negative Breast Cancer

Sponsor: University of Texas Southwestern Medical Center (other) Phase: 1 Start date: April 20, 2022

HealthScout AI summary: This trial enrolls adults with unresectable stage III or IV HER2 negative metastatic breast cancer (including both triple negative and hormone receptor positive disease) who have progressed after prior therapy, testing the combination of pegylated liposomal doxorubicin with the CD40 agonist antibody CDX-1140 and the Flt3 ligand CDX-301 (a dendritic cell growth factor) to evaluate safety and early efficacy. All participants ultimately receive all three agents, with sequencing varying by cohort.

ClinicalTrials.gov ID: NCT05029999