On July 6, 2022 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of conditionally activated oncology therapeutics, reported that the Phase 2 study of praluzatamab ravtansine in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-non-amplified breast cancer (Arm A) met its primary efficacy endpoint of confirmed objective response rate (ORR) of greater than 10 percent by central radiology review (Press release, CytomX Therapeutics, JUL 6, 2022, View Source [SID1234616502]). Praluzatamab ravtansine is a DM4-conjugated, conditionally activated antibody-drug conjugate (ADC) targeting CD166 and is wholly owned by CytomX.
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As of the data cutoff on May 13, 2022, 47 patients unselected for CD166 expression with advanced HR+/HER2-non-amplified breast cancer were evaluable for the primary efficacy endpoint. The ORR by central radiology review was 15 percent. Clinical benefit rate at 24 weeks by investigator (CBR24), as defined in the protocol as any response (confirmed or unconfirmed) or stable disease for 24 weeks, was 40 percent; median progression-free survival was 2.6 months. All patients in Arm A were treated at the initial Phase 2 starting dose of 7 mg/kg administered every three weeks. Arm B did not pass protocol-defined futility boundary (ORR was less than 10%) in patients with advanced triple-negative breast cancer (TNBC) and enrollment into Arms B and C will be discontinued.
As of this data cut, the safety profile of praluzatamab ravtansine in Arm A was generally consistent with toxicities observed in Phase 1 and with the DM4 payload; namely, high-grade toxicities or toxicities resulting in dose modifications were predominantly ocular or neuropathic in nature. Thirty percent of patients discontinued treatment for an adverse event (AE). Grade 3+ ocular and neuropathic toxicities were 15 and 10 percent, respectively. Arm B evaluated both 7 mg/kg and 6 mg/kg in patients with TNBC. The toxicity profile of 7 mg/kg starting dose was consistent with Arm A. In the 6 mg/kg cohort, no patients discontinued treatment for an AE and Grade 3+ ocular or neuropathic related events were lower at 3, and 0 percent, respectively. Biomarker analysis is ongoing. CytomX intends to submit data from this study for presentation at a medical conference in the second half of 2022.
"These results from our Phase 2 evaluation of praluzatamab ravtansine support single-agent activity of this novel drug candidate in hormone receptor-positive breast cancer where significant unmet need remains," said Sean McCarthy, D.Phil., chief executive officer and chairman at CytomX Therapeutics. "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."
Kathy D. Miller, MD, Ballvé Lantero Professor of Oncology, Indiana University Simon Comprehensive Cancer Center, Indianapolis, Indiana, and lead investigator of the Phase 2 study stated, "In this Phase 2 study, praluzatamab ravtansine showed single-agent activity in an unselected population of patients with advanced HR+/HER2-non-amplified breast cancer; additional clinical studies at 6 mg/kg are warranted."
Conference Call & Webcast
CytomX management will host a conference call and a simultaneous webcast today at 5:00 pm ET (2:00 pm PT) to discuss these results. Participants may register for the conference call here and are advised to do so at least 10 minutes prior to joining the call. A live webcast of the call can be accessed via the Events and Presentations page of CytomX’s website at View Source
About Praluzatamab Ravtansine
Praluzatamab ravtansine is a conditionally activated antibody-drug conjugate (ADC) comprised of a CD166-directed humanized monoclonal antibody conjugated to the maytansinoid DM4, a tubulin inhibitor. Praluzatamab ravtansine utilizes CytomX Probody platform technology, which incorporates a masking peptide to cover and block 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 ADC to be unmasked and engage its target to deliver the toxic DM4 payload inside tumor cells. The goal is to have praluzatamab ravtansine remain inert while in circulation to limit binding in healthy tissues until it is activated by tumor-associated proteases. Praluzatamab ravtansine was evaluated in a three-arm Phase 2 study (NCT04596150) in patients with hormone receptor-positive/HER2-non-amplified breast cancer and patients with triple-negative breast cancer.
About the Phase 2 Study of Praluzatamab Ravtansine in Breast Cancer (NCT04596150)
Arm A of the study evaluated praluzatamab ravtansine as monotherapy (7 mg/kg, Q3W) in patients with inoperable, locally advanced or metastatic hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-non-amplified breast cancer. Patients received 0 to 2 prior cytotoxic chemotherapies in the inoperable, locally advanced, or metastatic setting, regardless of the level of CD166 expression.
Arm B assessed praluzatamab ravtansine as a single agent (6 or 7 mg/kg, Q3W) in patients with inoperable, locally advanced or metastatic triple-negative breast cancer (TNBC). Patients received 1 to 3 prior lines of chemotherapy for inoperable, locally advanced, or metastatic disease and had CD166 expression.
Arm C studied praluzatamab ravtansine (6 mg/kg, Q3W) in combination with pacmilimab (1200 mg, Q3W), CytomX’s proprietary conditionally activated anti-PD-L1 antibody, in patients with TNBC. Eligibility was the same as Arm B with the additional requirement that patients’ tumors were programmed death-ligand 1 (PD-L1)-positive by an FDA-approved test.