CytomX halts lead program and will seek a partner as breast cancer drug disappoints

2022-07-07

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Mixed Phase II results are forcing CytomX to slam the brakes on one of its lead cancer drugs — unless it can convince a partner to help take it further. The data come from a study of praluzatamab ravtansine, CytomX’s take on a CD166-targeting antibody-drug conjugate, in breast cancer that comprised three separate arms: Arm A focused on hormone receptor-positive, HER2-non-amplified patients; Arm B and C both recruited patients with triple-negative breast cancer, but the former tested the drug as a monotherapy and Arm C gave it in combination with an in-house anti-PD-L1 drug dubbed pacmilimab. Investigators tracked positive results in Arm A, where the therapy met the primary endpoint with an overall response rate of more than 10%. Among 47 patients, the ORR was 15%, and on the secondary endpoints, clinical benefit rate at 24 weeks was 40% and median progression-free survival was 2.6 months. Arm B, however, failed to pass the futility boundary that CytomX set as ORR was less than 10%. As a result, the biotech says it will stop enrolling new patients into both Arms B and C. “It seems to us that conditional activation Probody technology has demonstrated technical utility but the results in HR+ breast cancer HR+ breast cancer make it challenging to see advancement given the competitive dynamics in the HR+ breast cancer HR+ breast cancer market, which has been a concern for us,” Mizuho analyst Mara Goldstein wrote in a note. “We don’t disagree with the decision to halt development, but we also do not have high expectations for a partnership.” In the wake of the setback, shares $CTMX fell 22% to $1.51 after the bell Wednesday. To make things more complicated, CytomX actually tested two different doses in the study: While Arm A exclusively gave 7 mg/kg, Arm B assessed both 6 mg/kg and 7mg/kg, and Arm C studied only the lower-dose regimen. In Arm A, 30% of patients discontinued treatment for an adverse event, and the company reported Grade 3+ ocular and neuropathic toxicities of 15% and 10%, respectively. In contrast, the 6 mg/kg dose was tied to much lower toxicity. “These results from our Phase II evaluation of praluzatamab ravtansine support single-agent activity of this novel drug candidate in hormone receptor-positive breast cancer where significant unmet need remains,” CEO Sean McCarthy said in a statement. “However, 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 has inked multiple alliances with Big Pharma partners over the years on the allure of its Probody technology, which centers around a masking peptide on drugs allowing for activation under the right conditions, theoretically alleviating safety concerns. Praluzatamab ravtansine, also known as CX-2009, is often referred to as a Probody-drug conjugate because it uses one such conditionally activated antibody to home in on cancer. The antibody is conjugated to the maytansinoid DM4, a tubulin inhibitor. But the Probody tech has yet to lead to any marketed drug and Pfizer chose to drop out of its deal in 2018. Others like AbbVie, Bristol Myers Squibb, Amgen and Astellas, though, are moving forward with various candidates. CytomX says it will continue to analyze biomarker data and plans to present more findings later. The company’s next data readout will come from the AbbVie-partnered CX-2029, a Probody-drug conjugate that targets CD71, in squamous non-small cell lung cancer.

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