On December 20, 2021 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of conditionally activated therapeutics, reported preliminary Phase 2 results in patients with either advanced squamous non-small cell lung cancer (sqNSCLC) or head and neck squamous cell carcinoma (HNSCC), who were treated with CX-2029 – a CD71-directed conditionally activated antibody-drug conjugate (ADC) being co-developed by CytomX and AbbVie (Press release, CytomX Therapeutics, DEC 20, 2021, View Source [SID1234597454]).

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"We are pleased to report these first results from the ongoing Phase 2 expansion study of CX-2029, a novel ADC developed with the CytomX Probody Therapeutic platform. We are encouraged that the response rate in heavily-pretreated and unselected sqNSCLC patients at this recent data cut off is trending with our stated target of 20% and enrollment in this tumor type continues towards our goal of 25 efficacy-evaluable patients. No new safety signals were observed and we are also encouraged by the low discontinuation rate due to adverse events. These preliminary results corroborate our previous Phase 1 observations and open a potential sqNSCLC commercial opportunity in the growing post-checkpoint inhibitor setting where there are limited treatment options," said Sean McCarthy, D.Phil., president, chief executive officer and chairman of CytomX Therapeutics. "We continue to work closely with our partner, AbbVie, and look forward to completing the expansion phase of the CX-2029 development program and providing further data updates in 2022."

As of the data cutoff on October 29, 2021, 23 patients with sqNSCLC and 29 patients with HNSCC had received at least one dose of CX-2029 at 3 mg/kg (safety population), of whom 16 sqNSCLC patients and 25 HNSCC patients had at least one post baseline assessment (efficacy-evaluable population), including, per protocol, 5 patients (2 sqNSCLC and 3 HNSCC) enrolled in the previously reported Part B (tumor biopsy cohorts). The median follow-up time was 3.8 months (range, 0.2-20.1). In the 16 efficacy evaluable patients with sqNSCLC, objective response rate (ORR) by local investigator was 18.8 percent, including two confirmed partial responses (PRs) and one unconfirmed PR that confirmed seven days after the data cutoff. Two of these responses were ongoing and the third had a response duration of 5.6 months. The disease control rate (DCR), which includes patients with a complete response, PR or stable disease, was 87.5 percent. In the 25 efficacy evaluable patients with HNSCC, there was one confirmed PR (ORR 4.0%) and a DCR of 56.0 percent, including one unconfirmed PR. Below is a summary table.

sqNSCLC HNSCC
Safety Evaluable Efficacy Evaluable Confirmed PR Safety Evaluable Efficacy Evaluable Confirmed PR
Part B 2 2 1 3 3 1
Part C 21 14 2* 26 22 0**
Total 23 16 3 29 25 1
ORR 18.8% 4.0%
*Includes one unconfirmed PR that confirmed after the data cutoff. **One unconfirmed PR was observed (will not confirm).

Safety analysis was conducted on all sqNSCLC and HNSCC patients who received at least one dose of CX-2029 at 3 mg/kg (N=52), either in Part B (N=5), or in the expansion cohorts (N=47). The median number of prior therapies in the metastatic setting was two (range, 1-5) for sqNSCLC and three (range, 1-9) for HNSCC. All patients with sqNSCLC had received prior platinum and prior checkpoint inhibition; in HNSCC, all but one patient received prior platinum and all but two, prior checkpoint inhibition.

The safety profile was consistent with previous Phase 1 observations, with no new safety signals identified. The most common treatment-related adverse events (TRAEs) in 10% or more of patients (All Grade, Grade 3) were anemia (78.8%, 67.3%), infusion related reactions (69.2%, 3.8%), fatigue (19.2%, 1.9%), and nausea (13.5%, 0.0%), and decreased neutrophil count (13.6%, 9.6% (plus one Grade 4 event 1.9%)). The most common reason for treatment discontinuation was disease progression (44.2%), three patients (5.8%) discontinued for a treatment-related adverse event (anemia; 2 Grade 2, 1 Grade 3). TRAEs leading to dose interruption or reduction were 40.4% and 34.6%, respectively. Thirteen patients, eight with sqNSCLC and five with HNSCC, were still on treatment as of the data cut off.

Conference Call & Webcast
CytomX management will host a conference call and a simultaneous webcast today at 5 p.m. ET (2 p.m. PT) to discuss these results. To join the conference call, please dial (877) 809-6037 (domestic) or (615) 247-0221 (international) and reference the conference ID 8065625. A live webcast of the call can be accessed via the Events and Presentations page of CytomX’s website at View Source A replay of the webcast will also be available for 30 days following the call.

About CX-2029
Co-developed by CytomX and AbbVie, CX-2029 is a conditionally activated antibody-drug conjugate (ADC) comprised of a CD71-directed humanized monoclonal antibody conjugated via a cleavable linker to the microtubule inhibitor, monomethyl auristatin E (MMAE), with a drug-to-antibody ratio (DAR) of 2. A key feature of CX-2029 is its masking peptide, which covers and blocks the cellular binding region of the antibody. Tethered to the antibody via a protease-cleavable linker, the masking peptide is designed to be removed in a protease-rich tumor microenvironment, enabling the then unmasked ADC to engage its target and deliver the toxic payload inside tumor cells. The goal is to have CX-2029 remain inert while in circulation, with the intent of limiting binding in healthy tissues until it is activated by tumor-associated proteases. CX-2029 is being evaluated as monotherapy in a Phase 2 expansion study (NCT03543813) designed to enroll patients in four cohorts; squamous non-small cell lung cancer, squamous head and neck cancer, esophageal and gastroesophageal junction cancers (both adenocarcinoma and squamous histologies), and diffuse large B-cell lymphoma.