CytomX and Amgen’s T cell engager showed mixed efficacy signals in an early trial in advanced solid tumors, sending the biotech’s shares down 37% even as analysts defended the data.
The Phase 1a dose-escalation study tested CX-904 — which targets the epidermal growth factor receptor (EGFR) and CD3 receptor — in patients with advanced metastatic solid tumors known to express EGFR. The trial enrolled 35 heavily pretreated patients with a median four prior lines of therapy at the data cutoff, according to a company release.
All six evaluable pancreatic cancer patients achieved disease control, including two with a confirmed partial response who had 85% and 51% tumor reductions, respectively. A third pancreatic cancer patient “maintained stable disease with no evidence of tumor growth” for three and a half months of study treatment, the company said.
CX-904 had a “favorable” safety profile with no cases of cytokine release syndrome (CRS) of any grade observed in the step-dosing cohorts, according to the company. There was some low-grade CRS in non-step dosing patients treated with the highest 6 mg dose.
Nonetheless, CytomX shares $CTMX sat at $2.60 premarket Thursday, down from Wednesday’s close of $4.19.
The companies are set to report more data by the end of the year, after which Amgen will decide whether to move the drug forward.
The Amgen-allied program is currently CytomX’s most advanced, after the biotech’s other partners, including Bristol Myers Squibb and AbbVie, dropped other clinical-stage candidates.
Amgen started co-developing CX-904 after inking a $1.5 billion package deal with CytomX back in 2017, featuring $40 million upfront. The drug candidate was designed using CytomX’s Probody platform, which adds a “masking” peptide to T cell bispecifics to limit their ability to bind to healthy tissue, thereby reducing toxicities.
“We are encouraged by the early data, particularly for the safety that validates [CytomX’s] masking tech platform and supporting higher doses,” Jefferies analysts said Thursday, adding that some “overblown” investor concerns have nonetheless “put pressure” on company shares.
Sean McCarthyThe first concern relates to the lack of efficacy in 13 evaluable colorectal cancer patients, only two of whom had tumor reductions upon treatment, according to a company presentation. But colorectal cancer is a “tough-to-treat” cold tumor for any immunotherapy, the analysts wrote. “Not a lot of progress has been made with T cell engagers yet in CRC so we would be looking to combination strategies there,” CEO Sean McCarthy said on a Wednesday call.
Another concern is unclear dose-dependent efficacy, the Jefferies analysts wrote. In the CRC cohort, the three patients who achieved stable disease were treated with the 0.75 mg, 1.5 mg and 5 mg doses, respectively, but most other patients had progressive disease irrespective of their treatment dose. The analysts said that while numbers are small, responses are still occurring at higher doses in the trial as a whole.
Editor’s note: This article was updated to clarify that both Amgen and CytomX will report more data from the Phase 1a trial by the end of the year.