Dive Brief:
- San Francisco-based CytomX Therapeutics impressed investors Monday with the latest results for its experimental antibody-drug conjugate in hard-to-treat, late-stage colorectal cancer.
- The fresh data come from a so-called expansion portion of an ongoing Phase 1 study, which has been testing CytomX’s “masked” ADC. This portion evaluated three doses of the drug, dubbed Varseta-M, and found the two highest had response rates of 20% to 32% and extended progression-free survival by 6.8 and 7.1 months. The most common treatment-related adverse event was diarrhea, which, CytomX said, was generally manageable and reversible. However, despite an updated prophylactic regimen, 10% of a group of 20 patients still experienced severe diarrhea.
- The company said more data will be announced at upcoming medical meetings this year, and plans to engage with the Food and Drug Administration to determine a study design to evaluate the medicine as a monotherapy in advanced colorectal cancer.
Dive Insight:
CytomX previously decided to pivot away from some of its work on ADCs, a type of drug linking a toxic payload to a targeting molecule to deliver a precise attack to tumors, to focus on other candidates.
However, its lead program is an ADC with a slightly different approach to tumor targets. Varseta-M is referred to as a “masked, conditionally activated” ADC, taking aim at the epithelial cell adhesion molecule, or EpCAM, that is expressed in tumors considered “undruggable.” Varseta-M operates by opening a “therapeutic window” for the anti-EpCAM activity to work.
The drug is being assessed across stages of colorectal cancers, a type of malignancy that typically affects older adults but has been rising among younger populations. Late-stage metastatic colorectal cancer can be challenging to control, as cancer cells spread to other parts of the body. It involves various types of treatment, with systemic therapy being the primary approach.
In May, CytomX announced positive interim data from its Phase 1 dose escalation trial of Varseta-M in patients with advanced colorectal cancer. The data announced Monday provide the most substantial update yet for the masked ADC.
“These latest Phase 1 data reinforce the potential of Varseta-M to meaningfully improve the standard of care in late-line colorectal cancer,” said Sean McCarthy, CEO and chairman of CytomX, in a statement.
On March 8, ahead of the new results, Cantor Fitzgerald analysts Olivia Saunders and Sam Rodriguez wrote that most investors feel “reasonably good about efficacy,” but the “real debate is around tolerability given the historical challenges with EpCAM-targeted approaches.”
The Cantor team added that, while efficacy matters, the drug's commercial performance will depend on high grades of diarrhea, with a 20% Grade 3 — or severe — rate being a commercially viable profile. “But given that it was ~22-23% without loperamide prophylaxis, investors want to see that number come down in this data cut.”
Saunders and Rodriguez view Varseta-M as a “$750 million peak opportunity” in metastatic colorectal cancer that has progressed after three prior lines of systemic chemotherapy
CytomX shares soared about 66% in early morning trading Monday.
