On June 21, 2021 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a clinical-stage oncology-focused biopharmaceutical company pioneering a novel class of investigational conditionally activated therapeutics based on its Probody technology platform, reported that results from its Phase 1 first-in-human study of CX-2029 in patients with advanced solid tumors were published online in the peer-reviewed journal Clinical Cancer Research (Press release, CytomX Therapeutics, JUN 21, 2021, View Source [SID1234584185]). This study showed that CX-2029, currently being co-developed by CytomX and AbbVie, was generally well-tolerated and can elicit anti-tumor responses in certain patients.
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"These results highlight that our industry-leading Probody platform can be successfully leveraged to create conditionally activated ADCs against previously undruggable targets. For the first time, CD71 has been shown to be a viable therapeutic cancer target," said Alison L. Hannah, M.D., senior vice president and chief medical officer of CytomX Therapeutics.
CD71 is a cell surface protein essential for iron uptake in dividing cells and is highly expressed in a number of solid and hematologic cancers. However, given its central role in iron metabolism, CD71 is present on most healthy cells and has been, until now, undruggable with conventional ADCs. CX-2029 is designed to be activated in the tumor microenvironment by tumor-associated proteases, thereby limiting off-tumor toxicity and creating a therapeutic window for CD71.
The goal of this Phase 1 dose-escalation, multicenter study was to evaluate the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of CX-2029. A total of 45 patients were enrolled to receive CX-2029 intravenously every three weeks at dose levels ranging from 0.1 mg/kg to 5 mg/kg.
Encouraging preliminary clinical activity was observed at doses of 2 mg/kg and higher. Notably, three of four patients with squamous non-small cell lung carcinoma (NSCLC) had stable disease (SD) or better, including two confirmed partial responses (PRs) (at doses of 3 and 5 mg/kg); and seven of eight patients with head and neck squamous cell carcinoma (HNSCC) had SD or better, including one confirmed PR at 3 mg/kg and one prolonged SD ongoing at approximately 25 weeks, as of the reported August 2020 data cutoff.
Despite having received a median of three prior lines of cancer regimens (range, 1–16), these heavily-pretreated patients generally tolerated CX-2029 well. The most common dose-dependent adverse events were anemia and neutropenia, toxicities commonly associated with the payload of this ADC (monomethyl auristatin E). Based on several safety parameters, including no cycle 1 DLTs, no discontinuations due to toxicity, and a long-term tolerability that appeared to be acceptable for chronic administration with supportive care for anemia, 3 mg/kg every 3 weeks was declared the recommended Phase 2 dose.
The ongoing Phase 2 expansion study is evaluating CX-2029 as monotherapy in four cohorts: squamous NSCLC, HNSCC, esophageal and gastroesophageal junction cancers (both adenocarcinoma and squamous histologies), and diffuse large B-cell lymphoma. Initial results are expected in the fourth quarter of 2021.