Shares of Celldex Therapeutics Inc. gained 25.5 percent Monday – a reaction to the company reporting positive final data on CDX-011 in a Phase II study in metastatic breast cancer.

Results were presented Saturday at the San Antonio Breast Cancer Symposium (SABCS) and build on interim data released in May. (See BioWorld Today, May 25, 2012.)

The firm's targeted therapy, CDX-011 (glembatamumab vedotin), is an antibody-drug conjugate (ADC) that targets and binds to GPNMB, a specific protein that is expressed in breast cancer, which promotes the migration, invasion and metastasis of the disease.

CDX-011 consists of a fully human monoclonal antibody, CR011, linked to the drug monomethyl-auristatin E (MMAE). The ADC technology, comprising MMAE and a stable linker system for attaching it to CR011, was licensed from Seattle Genetics Inc.

The final results were from the company's randomized Phase IIb EMERGE study of CDX-011 in patients with glycoprotein NMB (GPNMB)-expressing, advanced, heavily pretreated breast cancer. The protein also is highly expressed in triple-negative breast cancers where it is associated with increased risk of recurrence.

"We are very pleased with the clinical data from what was a heavily treated breast cancer patient population," Anthony Marucci, president and CEO of Celldex, told BioWorld Today. "The median number of prior courses of therapy for the CDX-011 arm was six, and on the investigator's choice arm, the median number of prior courses of therapy was five."

A total of 122 patients were treated in the study, with 81 patients randomized to the CDX-011 arm and 41 patients to the investigator's choice (IC) single-agent chemotherapy arm, of which 15 later crossed over to receive CDX-011 . In total, 81 CDX-011 patients (including crossovers) and 36 IC patients had on-study radiographic assessments and were evaluable for response. Nearly all patients had Stage IV, or metastatic, disease.

Treatment of patients with both triple-negative breast cancer and high GPNMB expression showed high overall response rates for the CDX-011 arm (CDX-011 ORR of 33 percent vs. 0 percent in the IC arm) and an overall survival and progression-free survival benefit (PFS) for CDX-011 that reached statistical significance (CDX-011 median survival of 10 months vs. IC of 5.5 months).

In patients with high GPNMB expression, a high response rate was observed in the CDX-011 arm (CDX-011 ORR of 32 percent vs. IC of 13 percent) and a trend of improvement in overall survival and PFS was demonstrated for the CDX-011 arm.

The company is hoping that those results will lead to an accelerated approval pathway for the targeted therapy, and Marucci said Celldex will be having discussions with the FDA before the end of the year.

"CDX-011 was one of the promising antibodies identified from CuraGen Corp.'s genomics database, which we added to our pipeline through the acquisition of the company in 2009," Marucci said. (See BioWorld Today, June 1, 2009.)

According to Thomas Davis, chief medical officer at Celldex, a number of research groups have been trying to understand the biology of GPNMB. Peter Siegel and a team of researchers at the Department of Medicine, for example, identified that GPNMB expression is associated with the basal/triple-negative subtype and is a prognostic marker of worst outcomes in patients with breast cancer.

Other researchers have shown that it is active in bone metabolism, and tumors that overexpress GPNMB are more likely to metastasize to bone, he added.

The results presented, the company said, establish proof of principle with evidence of higher activity in patient subgroups with high GPNMB expression (expression in 25 percent or greater of tumor cells), including those with triple-negative disease, an aggressive subtype of breast cancer that is associated with poor disease outcome. According to estimates, about 20 percent of breast cancer patients have triple-negative disease, with about 35 percent of those patients expressing GPNMB.

Although those data likely will have to be confirmed in a larger pivotal study, it appears that CDX-011 could be a promising new targeted therapy for patients with metastatic triple-negative breast cancers, a patient population that currently lacks any targeted therapy options.

Celldex's shares (NASDAQ:CLDX) closed at $6.93 Monday.

In other SABCS news:

• Adherex Technologies Inc., of Research Triangle Park, N.C., presented preliminary interim data from a Phase II trial testing its eniluracil in combination with 5-FU and leucovorin (EFL) in metastatic breast cancer patients who had rapid disease progression on capecitabine treatment. Data showed that 89 percent had clinical benefit, 33 percent had tumor responses and patients on EFL had ongoing median progression-free survival of 117 days vs. 42 days for capecitabine. Final efficacy and safety data are expected in the second quarter of 2013. Eniluracil is a mechanism-based inactivator of DPD, the enzyme that breaks down 5-FU. Shares of Adherex (OTCBB:ADHX) fell 15 cents, or 22.3 percent, to close Monday at 51 cents.

• Genentech Inc., of South San Francisco, a member of the Roche Group, reported updated survival results from the Phase III CLEOPATRA trial, showing that the combination of Perjeta (pertuzumab), Herceptin (trastuzumab) and docetaxel chemotherapy significantly extended the lives of people with previously untreated HER2-positive metastatic breast cancer, compared to Herceptin, chemotherapy and placebo. Results showed that the risk of death was reduced by 34 percent for people in the Perjeta arm (p = 0.0008). At the time of analysis, median overall survival in the Perjeta arm had not been reached. Perjeta was approved earlier this year based largely on progression-free survival data from the CLEOPATRA study. (See BioWorld Today, June 12, 2012.)

• Merrimack Pharmaceuticals Inc., of Cambridge, Mass., reported Phase I results showing that MM-302, a nanotherapeutic encapsulation of anthracycline chemotherapy doxorubicin with anti-HER2 antibody fragments attached to its surface, was found to be safe and tolerable. Of the 22 evaluable patients in the heavily pretreated breast cancer population, 12 achieved stable disease and two patients achieved a partial response, for a total clinical benefit rate of 64 percent. Meanwhile, a study of a potential companion imaging diagnostic was shown to predict treatment response in preclinical models.

• Puma Biotechnology Inc., of Los Angeles, reported results from an ongoing Phase II trial showing that PB272 (neratinib) in combination with temsirolimus had acceptable tolerability in patients with HER2-positive metastatic breast cancer with disease progression on Herceptin (trastuzumab, Roche AG). Efficacy results showed that for the 27 evaluable patients, 12 (44 percent) experienced a partial response and one patient (4 percent) experienced prolonged stable disease for greater than six months, for a clinical benefit rate of 48 percent. Patients who experienced partial responses to the combination treatment demonstrated a maximum change in the size of their target lesions of between 33 percent and 83 percent.