CytomX Therapeutics Presents Clinical Data From Probody Platform

CytomX Therapeutics, Inc. recently presented clinical results from two arms of the PROCLAIM (PRObody CLinical Assessment In Man) module, PROCLAIM-072. PROCLAIM-072 is an ongoing Phase 1/2 trial evaluating CX-072, a Probody therapeutic targeting PD-L1, as monotherapy and in combination with Yervoy (ipilimumab) or Zelboraf (vemurafenib) in patients with advanced, unresectable solid tumors. Data from the CX-072 monotherapy arm and ipilimumab combination arm were presented in two posters at the 2018 Annual Meeting of the European Society of Clinical Oncology (ESMO) in Munich, Germany. The data presented at ESMO were based on an August 3, 2018 data cut-off, reflecting an approximately three-month difference from the data cutoff for the presentations made at the American Society of Clinical Oncology (ASCO) Annual Meeting in June.

“Our data presented today continue to support our thesis that CX-072 has potential to be a new and differentiated combination partner for anti-cancer therapy. CX-072 has demonstrated activity both as monotherapy and in combination with ipilimumab and is generally well tolerated in both regimens,” said Sean McCarthy DPhil, President and Chief Executive Officer of CytomX Therapeutics. “We are advancing monotherapy CX-072 toward registrational studies and continuing to explore the full potential of the CX-072/ipilimumab combination. With the clinical data reported today, and at ASCO, the Probody platform is declaring its potential to deliver multiple opportunities to make a meaningful difference for cancer patients.”

The primary objectives of Parts A and A2 of this first-in-human, dose-escalation, monotherapy arm are to assess safety and tolerability, including determination of the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT) of CX-072 as monotherapy. Patients in Part A received escalating doses of CX-072 from 0.03 mg/kg to 30 mg/kg. Patients in Part A2 received escalating doses of CX-072 from 0.3 mg/kg to 10 mg/kg and had mandatory biopsies of PD-L1 positive solid tumors. At the time of the August 3, 2018 data cutoff, Parts A and A2 had enrolled 46 patients, with 11 patients still receiving treatment. Treatment duration for patients in Part A2 was limited at higher doses. Enrollment in Part A is complete and Part A2 is ongoing with patient follow-up ongoing.

The maximum tolerated dose (MTD) was not reached. As of an August 3, 2018, data cut-off, results were consistent with previous analyses. The administration of monotherapy CX-072 was generally well tolerated with the majority of treatment-related adverse events (TRAEs) Grade 1/2. Of the 46 treated patients, 5 (11%) reported Grade 3/4 TRAEs and 3 (7%) reported treatment-related serious adverse events (SAEs). Immune-related adverse events (irAE) were reported in 3 (7%) of patients.

As of an August 3, 2018, data cut-off, results showed that among 38 evaluable patients who received CX-072, objective responses by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 were observed in 3 (8%) patients, all treated at a dose of > 3 mg/kg: PD-L1 negative triple negative breast cancer (confirmed partial response (cPR); 10 mg/kg), thymic cancer (unconfirmed partial response (uPR); 3 mg/kg), and cervical cancer (uPR; 10 mg/kg).  Stable disease was observed in 15 (39%) of patients for an overall disease control rate of 47%. For the 18 patients who received CX-072 ≥3 mg/kg, objective responses were observed in 3/18 (17%) and the disease control rate was 61%. Decreased target lesions were observed in 38% (14/37) of all evaluable patients with measurable disease at baseline and in 59% (10/17) of the subset of patients who received > 3 mg/kg of CX-072.

The primary objectives of this ongoing arm of the study are to assess safety and tolerability, and to determine the MTD and DLT of CX-072 when administered in a concomitant combination schedule with ipilimumab. At the August 3, 2018 data cutoff, the study had enrolled 20 immunotherapy naïve patients who had received an average of 3 prior anti-cancer treatments in a variety of tumor types for which no anti-PD-1 or PD-L1 agents were available for their disease. Patients received the combination ipilimumab (3 mg/kg or greater) and CX-072 (escalating doses of 0.3 mg/kg to 10 mg/kg) every three weeks for four cycles followed by monotherapy CX-072 every two weeks.

As of the August 3, 2018, data cut-off date, the MTD had not yet been reached and was generally well tolerated with no new safety signals observed beyond those expected for each component of the CX-072 plus ipilimumab combination. The full dose of 3 mg/kg of ipilimumab in combination with CX-072 10 mg/kg was well tolerated. The majority of TRAEs were Grade 1/2.  Of the 20 treated patients, 4 (20%) reported a Grade 3/4 TRAE, a rate similar to that reported previously for 3 mg/kg ipilimumab monotherapy. These events included: Grade 3 colitis (n=1), Grade 3 dyspnea/Grade 3 pneumonitis (n=1), Grade 3 headache/Grade 3 hyponatremia (n=1), and Grade 3 amylase/Grade 4 lipase (n=1). Grade 3/4 irAEs were reported in 2/20 (10%) patients, 0% (0/11) at doses of >3 mg/kg CX-072 with 3 mg/kg of ipilimumab. The study is still ongoing with enrollment and dose escalation continuing.

As of an August 3, 2018, data cut-off, results also showed that among 14 evaluable patients who received ipilimumab (3 mg/kg) combined with CX-072 (0.3 to 10 mg/kg), 3 (21%) achieved objective responses by RECIST v1.1, including patients with: anal cancer (confirmed complete response (cCR); 0.3 mg/kg CX-072), testicular cancer (confirmed partial response (cPR); 1 mg/kg CX-072) and cancer of unknown primary (cPR; 3 mg/kg CX-072).  Stable disease was observed in 3 additional patients for a disease control rate of 43%.  As of the data cutoff, all 3 of the responders remained on treatment with durations of response of 7.4, 5.3, and 3.2 months, respectively.

Results from a preliminary single-dose pharmacokinetic analysis of single-agent CX-072 suggest that, as designed, CX-072 circulates predominantly as the intact masked prodrug across all dose levels with 96% intact at 30 mg/kg. Further, CX-072 is only minimally influenced by target mediated drug disposition at low doses, suggesting that masking is effective in blocking interaction with PD-L1 in the periphery.

Based upon the results from the Part A CX-072 monotherapy arm presented at ASCO in June, in the second quarter, the Company began dosing patients in Part D, the expansion arm examining CX-072 as monotherapy at 10 mg/kg in 8 undisclosed tumor types. The Company has the potential to move one or more of these indications into a registrational trial with the goal of advancing towards commercialization. The Company expects initial Part D clinical data in 2019.

The company is currently dosing patients in the Part B CX-072 combination with ipilimumab arm at 6 mg/kg of ipilimumab. The Company plans to initiate expansion modules with this combination in the first half of 2019 at doses and indications to be determined.

CytomX Therapeutics is a clinical-stage oncology-focused biopharmaceutical company pioneering a novel class of investigational antibody therapeutics based on its Probody therapeutic technology platform. Probody therapeutics are designed to exploit unique conditions of the tumor microenvironment to more effectively localize antibody binding and activity while limiting activity in healthy tissues. For more information, visit www.cytomx.com.