CytomX puts lead ADC on the block after phase 2 breast cancer data underwhelm

CytomX Therapeutics is pulling the plug on its lead candidate after getting a look at phase 2 data. One of the arms hit its primary endpoint, but the data fell short of the bar CytomX set for further development, leading it to halt work and seek a partner for the prospect.

Investigators assigned patients with hormone receptor-positive, HER2-negative breast cancer to receive 7 mg/kg of the CD166-directed antibody-drug conjugate (ADC) praluzatamab ravtansine. The other two arms enrolled triple-negative breast cancer patients, with participants in arm B receiving 6 mg/kg or 7 mg/kg of the ADC as a single agent and their counterparts in arm C taking 6 mg/kg in combination with CytomX’s anti-PD-L1 antibody pacmilimab.

In arm A, more than 10% of participants had confirmed objective responses, causing that part of the trial to hit its primary endpoint. However, the response rate in arm B was below the 10% futility threshold, prompting CytomX to stop enrollment in both of the triple-negative breast cancer arms. 

CytomX shared more data from arm A that raised doubts about the use of the 7 mg/kg dose. While the response rate in the 47-subject arm hit 15%, clearing the primary endpoint threshold, progression-free survival came in at 2.6 months. The survival result contributed to CytomX pulling back from the higher dose. 

“We do not believe the median progression-free survival at 7 mg/kg supports further evaluation at this dose. While we are encouraged by the emerging safety profile of 6 mg/kg, we do not plan to further advance this program alone given current financial market conditions and will be seeking a partnership,” CytomX CEO Sean McCarthy said in a statement.

McCarthy’s focus on safety reflects the adverse events seen in the clinical trial. In arm A, which tested the higher of the two doses, 30% of participants discontinued treatment because of an adverse event. In keeping with CytomX’s phase 1 data, ocular and neuropathic toxicities were the chief concerns with, respectively, 15% and 10% of participants suffering grade 3 or worse adverse events. 

In arm B, the toxicity profile of the 7 mg/kg dose was consistent with arm A. At the lower, 6 mg/kg dose, no patients discontinued treatment for an adverse event or had a grade 3 or worse neuropathic adverse event. Three percent of participants on the lower dose had a grade 3 or worse ocular adverse event.

CytomX’s share price fell 27% to $1.43 after the release of the data. The setback leaves CytomX looking to clinical data on partnered programs for a boost. Updated phase 2 data on the AbbVie-partnered, CD71 ADC CX-2029 are due by the end of the year. Bristol Myers Squibb has a masked version of its anti-CTLA-4 antibody Yervoy based on CytomX tech in the clinic, too. CytomX had $263 million at the end of March.