Celldex Therapeutics Inc. (NASDAQ: CLDX) was another big mover coming out of the Annual Meeting for the American Society of Clinical Oncology (ASCO). Unfortunately, the move was to the downside. Celldex reported data from its Phase 1 portion of a Phase 1/2 dose escalation and cohort expansion study examining the combination of varlilumab, Celldex’s CD27, and Bristol-Myers Squibb Co.’s (NYSE: BMY) anti-PD-1 immunotherapy Opdivo (nivolumab) for the treatment of ovarian and colorectal cancer.
Combining varlilumab and Opdivo was well tolerated at all dose levels tested, without any evidence of increased autoimmunity or inappropriate immune activation.
The firms observed three partial responses (PR) in this portion of the trial. First a patient with PD-L1 negative, MMR proficient colorectal cancer, experienced a 95% decrease in target lesions, including resolution of 4/5 target lesions, one 6 mm mesenteric nodule remains. A Second patient with squamous cell head and neck cancer achieved a confirmed PR (59% shrinkage) and experienced progression free survival of 6.7 months. Finally, a patient with ovarian cancer experienced a single timepoint PR (49% shrinkage) but discontinued treatment to a dose-limiting toxicity.
The companies did note that continuous activation by immune agonists may not be optimal as it could lead to immune exhaustion and dampen the effect of combination therapy. The Phase 2 portion of this study includes alternate varlilumab dosing regimens to evaluate continuous versus intermittent immune activation at higher and lower dose levels and varied frequency. The Phase 2 portion of the study is expected to complete enrollment in early 2018.
Dr. Rachel Sanborn, co-director of the Providence Thoracic Oncology Program; and Phase I Clinical Trials Program, at the Earle A. Chiles Research Institute, Providence Cancer Center, commented:
Combining PD-1 inhibition with a potent T cell activating agent provides the opportunity to broaden the number of patients that benefit from checkpoint blockade. While early, we have evidence that this combination does not add toxicity, can turn some ‘immune-cold’ tumors hot, and may have clinical benefit, including in some patients who are not likely to respond to monotherapy. Further elucidating the role of intermittent versus chronic T cell activation through the comparison of alternate varlilumab dosing regimens is an essential component of the ongoing Phase 2 study and could be important in optimizing the potential of this combination.
Celldex shares were trading down 11.5% to $2.42 on Tuesday. The stock has a 52-week trading range of $2.37 to $5.02 and a consensus analyst price target of $6.50.
Shares of Bristol-Myers were last seen down 1% at $51.73, with a consensus price target of $57.18 and a 52-week range of $46.01 to $77.12.