CytomX forging ahead with just one breast cancer cohort, seeks partner
Business, R&D, TherapeuticsCytomX forging ahead with just one breast cancer cohort, seeks partner
Published: Jul 07, 2022
By Vanessa Doctor, RN
BioSpace
CytomX Therapeutics isn’t into exercises in futility. The Bay area-based biopharma company is discontinuing enrollment in two arms of its three-arm Phase II study of praluzatamab ravtansine in patients with triple-negative breast cancer (TNBC) after those studies failed to meet the protocol-defined futility boundary.
Arm B, which evaluated either 6 mg/kg or 7 mg/kg of the drug in patients with inoperable, locally advanced or metastatic TNBC and Arm C, which looked into using 6 mg/kg of the drug with 1200 mg of pacmilimab, will be halted.
Only Arm A, which evaluated praluzatamab ravtansine 7 mg/kg as monotherapy, will be considered, with future activity focused on lowering the dose to 6 mg/kg due to some observed toxicities. This trial demonstrated a clinical benefit rate of 40%, and the patients showed a median progression-free survival of 2.6 months.
Praluzatamab ravtansine is a DM4-conjugated, conditionally activated antibody-drug conjugate (ADC) that targets CD166, whose expression is linked with various cancers.
“We’re disappointed to have not seen more activity in triple-negative breast cancer but our work in Arms B and C has given important insight into the safety profile of praluzatamab ravtansine at 6 mg/kg,” Amy Peterson, M.D., president and chief operating officer of CytomX, said in the company’s web presentation.
As per the May 13 data cutoff in Arm A, 47 patients unselected for CD166 expression with advanced HR+/HER2-non-amplified breast cancer were evaluable for the primary endpoint of confirmed objective response rate by central radiology review, logging an ORR of 15%.
However, the Arm B cohort logged an ORR of less than 10%, which was the main reason for the halt that affected both arms B and C. In addition, 33% of the participants had to discontinue treatment, with 15% experiencing grade 3+ ocular toxicities and 10% experiencing neuropathic toxicities. Arms A and Arm B recorded similar toxicity issues, but only Arm A showed some promise in terms of ORR.
“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. This strategy will allow us to focus our resources on other areas of our clinical and preclinical pipeline,” Sean McCarthy, D.Phil., chief executive officer and chairman of CytomX said in the same presentation.
“When we selected the DM4 payload for this program, we did so with the expectation that payload-related toxicity would be observed. The antibody masking component of praluzatamab ravtansine is designed to minimize toxicities. If we take a step back and look at the totality of our achievements with [the drug], we can say that our masking technology has allowed us to target CD166. However, the optimization related to payload toxicities has proven harder than expected and more work is required. We believe this is best achieved with a partner,” McCarthy explained.
Details of the study will be discussed at a future medical presentation.
Source: BioSpace