Poster Session During the 2019 Annual Meeting of the American Association for Cancer Research. Photo Courtesy 2019 AACR.

Clinical and preclinical data for CX-2009, a Probody-drug Conjugate or PDC designed to target the cell surface protein CD166 and deliver the tubulin-destabilizing maytansine payload, DM4, to cancer cells, were presented at the annual meeting of the American Association for Cancer Research (AACR), held March 29 – April 3, 2019, in Atlanta, Georga.

CD166, the drugs target, is highly and homogeneously expressed on multiple tumor types. In preclinical studies, CD166 has been shown to effectively internalize antibody-drug conjugates or ADCs resulting in potent cell killing in vitro.

CX-2009, which is being developed by CytomX Therapeutics, has shown anti-cancer activity in multiple preclinical models.

?Collectively, these data presented during the annual meeting highlights the potential opportunity for CX-2009, a novel first-in-class CD166-targeting anti-cancer agent,? noted Sean McCarthy, D. Phil., president, chief executive officer and chairman of CytomX Therapeutics.

?In our first clinical dose escalation with CX-2009, we have seen clear evidence of tumor shrinkage in multiple cancers in heavily pretreated patients and an encouraging safety profile. The safety profile of CX-2009 is of particular note given the widespread expression of CD166 on normal tissues and suggests that CytomX masking technology can allow targeting of novel, broadly distributed antigens,” McCarthy explained.

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“Moreover, our preclinical and clinical research is revealing a relationship between target levels and anti-cancer activity, further validating CD166 as a potential new point of intervention in cancer treatment. In addition, our preclinical research into the combination of CX-2009 with a PD-1 Probody provides preliminary evidence for the potential of these two mechanisms to synergize with each other.

Proclaim studies

CX-2009 is being studied within Proclaim clinical trial program (PRObody CLinical Assessment In Man), an international modular umbrella clinical trial program that includes Phase I/II development of multiple Probody therapeutics.

Among the trials in the program is the PROCLAIM-CX-2009 study, is a dose-finding Phase I/II study evaluating CX-2009 as monotherapy in patients with select cancer types, including non-small cell lung cancer, breast cancer, ovarian cancer, endometrial cancer, cholangiocarcinoma (bile duct cancer), head and neck cancer and castration-resistant prostate cancer.

The objectives of the study are to establish the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of CX-2009.

Preliminary results

Preliminary results of PROCLAIM-CX-2009, a First-in-Human, Dose-Finding trial of Study CytomX Probody-drug Conjugate CX-2009 in patients with advanced solid tumors were presented by Funda Meric-Bernstam. MD., Chair of the Department of Investigational Cancer Therapeutics, Medical Director of the Institute for Personalized Cancer Therapy, and Professor, Divisions of Cancer Medicine and Surgery, MD Anderson Cancer Center [1]

Meric-Bernstam reported data from the dose-escalation phase (Part A and A2) of the ongoing PROCLAIM-CX-2009 study in seven selected tumor types. As of a February 26, 2019 data snapshot, 78 patients were enrolled. Of 71 patients evaluable for efficacy, for patients who received ?4 mg/kg of CX-2009 and had at least one post-baseline on-study tumor assessment, 15/39 (38%) achieved tumor shrinkage, including seven unconfirmed partial responses (4 patients with breast cancer, 2 with ovarian cancer and one with head and neck cancer). 29/39 (74%) achieved stable disease or better at the time of the first on-treatment scan.

CX-2009 was generally well tolerated. The maximum tolerated dose (MTD) was not reached at the highest dose level tested of 10 mg/kg. The most common treatment-related adverse events (TRAE) were grade 1 and 2 and included nausea (32%), fatigue (24%) and decreased appetite (23%). The most common grade 3/4 TRAE was keratitis (8%).

CX-2009 targeting PD-1

Anti-tumor activity of CX-2009 studied in a syngeneic mouse model showed that the combination treatment of CX-2009 with a surrogate mouse anti-PD-1 Probody significantly inhibited tumor growth in mouse CT-26 tumors engineered to express human CD166, as compared to either agent as a monotherapy.

In addition, CX-2009 was shown to induce immunogenic cell death of cancer cells in vitro while sparing T cells, an action that may enhance T-cell priming. These results, presented by Erwan Le Scolan, Ph.D., Senior Scientist at CytomX highlight the potential to combine the PDC CX-2009 with a Probody therapeutic targeting the PD pathway, such as the CytomX anti-PD-L1 Probody, CX-072, as well as potentially combining other antibody drug conjugates or PDCs with immune checkpoint inhibitors.

Treatment of Patient-derived Xenograft Models in a Mouse Clinical Trial Format

In a separate study researchers at CytomX evaluated the anti-tumor activity of CX-2009 in 198 PDX tumor models in a mouse clinical trial format dosed with 5 mg/kg of CX-2009 every 2 weeks for 3 doses.

As part of the study, 129 models (65%) had been dosed at the time of data cutoff. Results from the ongoing study, presented by Bob Liu, Ph.D., Senior Scientist at CytomX, showed anti-tumor activity in 82% of the models compared to control. Tumor shrinkage relative to pre-dosing was observed in 22% of models relative to untreated controls, and 48% of CX-2009-treated tumors yielded tumor growth inhibition of greater than 50%. CD166 mRNA level was associated with anti-tumor activity, which may provide a strategy for prospectively identifying patients most likely to respond to CX-2009.

“Based on these integrated observations presented at AACR 2019, we are excited to advance CX-2009 to the next phase of development,? CytomX McCarthy concluded.


[1] PROCLAIM-CX-2009: A Trial to Find Safe and Active Doses of an Investigational Drug CX-2009 for Patients With Selected Solid Tumors – NCT03149549 [Clinical Trial]

Last Editorial Review: April 3, 2019

Featured Image: Poster Session at the American Association for Cancer Research Annual Meeting, Sunday March 31, 2019. Courtesy:? 2010 ? 2019 AACR/Todd Buchanan. Used with permission.

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