A Phase l Open-Label, Dose Escalation and Cohort Expansion Study, to Assess the Safety and Activity of the Antibody-Drug Conjugate CDX-014 in Advanced or Metastatic Renal Cell Carcinoma (RCC) and Advanced or Metastatic Ovarian Clear Cell Carcinoma (OCCC)

This is a study to determine the safety of CDX-014 and effectiveness (how well the drug works).

Start Date01 Jun 2016

Sponsor / Collaborator

Celldex Therapeutics, Inc.

100 Clinical Results associated with CDX-014

100 Translational Medicine associated with CDX-014

100 Patents (Medical) associated with CDX-014

Literatures (Medical) associated with CDX-014

01 Dec 2020·Investigational New DrugsQ3 · MEDICINE

Safety and efficacy of CDX-014, an antibody-drug conjugate directed against T cell immunoglobulin mucin-1 in advanced renal cell carcinoma

Q3 · MEDICINE

Article

Author: Choueiri, Toni K ; Rogalski, Mark ; Keler, Tibor ; Hawthorne, Thomas ; McGregor, Bradley A ; Gordon, Michael ; George, Saby ; Flippot, Ronan ; Quinn, David I ; Agarwal, Neeraj

CDX-014 is an antibody-drug conjugate directed against TIM-1, a surface marker highly expressed in renal cell carcinoma (RCC) and ovarian carcinoma. This phase I, first-in-human trial was conducted to evaluate the safety and preliminary activity of CDX-014 in patients with advanced refractory RCC, following a dose-escalation and dose expansion design. CDX-014 was administered intravenously at doses ranging from 0.15 to 2.0 mg/kg every 2 or 3 weeks until progression or unacceptable toxicity. Sixteen patients received at least one dose of CDX-014. The maximum tolerated dose was not identified. Most frequent adverse grade 1 or 2 adverse events included nausea (38%), fatigue, alopecia, elevation of AST and decreased appetite (25% each). Adverse events of grade 3 or more included hyperglycemia (19%), urosepsis (6%), and one multi-organ failure (6%) responsible for one treatment-related death. Two patients discontinued therapy for adverse events including fatigue grade 2 and urosepsis grade 4. CDX-014 showed antitumor activity with one prolonged partial response and a clinical benefit rate (objective response or stable disease >6 months) of 31%. The two patients that exhibited the most marked tumor shrinkage had high TIM-1 expression on tumor tissue. Overall, CDX-014 exhibited a manageable toxicity profile and early signs of activity, supporting further evaluation of antibody-drug conjugates in patients with advanced RCC and potentially other TIM-1 expressing cancers. Trial registration https://clinicaltrials.gov/ct2/show/NCT02837991 NCT02837991; July 20, 2016.

01 Dec 2016·Molecular Cancer TherapeuticsQ2 · MEDICINE

Development of a Novel Antibody–Drug Conjugate for the Potential Treatment of Ovarian, Lung, and Renal Cell Carcinoma Expressing TIM-1

Q2 · MEDICINE

Article

Author: Forsberg, Eric M. ; Gergel, Lauren E. ; Pilsmaker, Catherine D. ; Crocker, Andrea ; Hammond, Russell A. ; Wallace, Paul K. ; Thomas, Lawrence J. ; Keler, Tibor ; Storey, James R. ; Vitale, Laura ; Minderman, Hans ; Boyer, James M. ; O'Neill, Thomas ; Sundarapandiyan, Karuna ; Widger, Jenifer ; Dolnick, Ree Y. ; Marsh, Henry C.

AbstractT-cell immunoglobulin and mucin domain 1 (TIM-1) is a type I transmembrane protein that was originally described as kidney injury molecule 1 (KIM-1) due to its elevated expression in kidney and urine after renal injury. TIM-1 expression is also upregulated in several human cancers, most notably in renal and ovarian carcinomas, but has very restricted expression in healthy tissues, thus representing a promising target for antibody-mediated therapy. To this end, we have developed a fully human monoclonal IgG1 antibody specific for the extracellular domain of TIM-1. This antibody was shown to bind purified recombinant chimeric TIM-1-Fc protein and TIM-1 expressed on a variety of transformed cell lines, including Caki-1 (human renal clear cell carcinoma), IGROV-1 (human ovarian adenocarcinoma), and A549 (human lung carcinoma). Internalization studies using confocal microscopy revealed the antibody was rapidly internalized by cells in vitro, and internalization was confirmed by quantitative imaging flow cytometry. An antibody–drug conjugate (ADC) was produced with the anti-TIM-1 antibody covalently linked to the potent cytotoxin, monomethyl auristatin E (MMAE), and designated CDX-014. The ADC was shown to exhibit in vitro cytostatic or cytotoxic activity against a variety of TIM-1–expressing cell lines, but not on TIM-1–negative cell lines. Using the Caki-1, IGROV-1, and A549 xenograft mouse models, CDX-014 showed significant antitumor activity in a clinically relevant dose range. Safety evaluation in nonhuman primates has demonstrated a good profile and led to the initiation of clinical studies of CDX-014 in renal cell carcinoma and potentially other TIM-1–expressing tumors. Mol Cancer Ther; 15(12); 2946–54. ©2016 AACR.

100 Deals associated with CDX-014

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Metastatic Clear Cell Renal Cell Carcinoma	Phase 2	US	Celldex Therapeutics, Inc.	01 Jun 2016
Metastatic Renal Cell Carcinoma	Phase 2	US	Celldex Therapeutics, Inc.	01 Jun 2016
Ovarian clear cell carcinoma	Phase 2	US	Celldex Therapeutics, Inc.	01 Jun 2016
Papillary Renal Cell Carcinoma	Phase 2	US	Celldex Therapeutics, Inc.	01 Jun 2016
Ovarian Cancer	Phase 2	US	Celldex Therapeutics, Inc.	-
Renal Cell Carcinoma	Phase 2	-	Amgen, Inc.	-
Renal Cell Carcinoma	Phase 2	US	Celldex Therapeutics, Inc.	-
Renal Cell Carcinoma	Phase 2	-	Celldex Therapeutics, Inc.	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02837991 (Pubmed \| Invest New Drugs) Manual	Phase 1	Advanced Renal Cell Carcinoma Third line	16	CDX-014	(rfisfjoeam) = The maximum tolerated dose was not identified. llkjjypszy (wynfglusdq ) View more	Positive	01 Dec 2020
NCT02837991 (ESMO2019)	Phase 1	Advanced Renal Cell Carcinoma	16	CDX-014	(obelbnrjew) = zxqhiihije salmbklbxd (dirslqwyix ) View more	-	30 Sep 2019

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

CDX-014

Overview

Basic Info

Structure

Gene Sequence

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation