Study to Evaluate the Safety and Antitumor Activity of CX-2009 Monotherapy and in Combination With CX-072 in Advanced Breast Cancer

• ClinicalTrials.gov Identifier: NCT04596150
• Recruitment Status: Active, not recruiting
• First Posted: October 22, 2020
• Last Update Posted: February 23, 2023
• Sponsor: CytomX Therapeutics
• Information provided by (Responsible Party): CytomX Therapeutics

Tracking Information

• First Submitted Date: October 2, 2020
• First Posted Date: October 22, 2020
• Last Update Posted Date: February 23, 2023
• Actual Study Start Date: December 29, 2020
• Estimated Primary Completion Date: April 30, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 15, 2020)

Objective Response Rate (ORR) [ Time Frame: 30 months ]

ORR is the proportion of patients in the efficacy-evaluable population with a best response of Complete Response (CR) or Partial Response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by Central Radiology Review (CRR)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 15, 2020)

• Investigator-assessed Progression-Free Survival (PFS) [ Time Frame: 30 Months ]
  The time from the date of the first dose of study treatment until documentation of objective tumor progression based on RECIST v1.1 or until death due to any cause
• Duration of Response (DoR) [ Time Frame: 30 Months ]
  The time that measurement criteria are met for CR or PR (based on RECIST v1.1) until the date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since treatment started)
• Overall Survival (OS) [ Time Frame: 30 Months ]
  The time from treatment initiation until death as a result of any cause
• Clinical Benefit Rate (CBR) at 16 Weeks [ Time Frame: 30 Months ]
  This will include sum of confirmed Complete plus Partial Responses plus stable disease at 16 weeks on treatment
• Clinical Benefit Rate (CBR) at 24 Weeks [ Time Frame: 30 Months ]
  This will include sum of confirmed Complete plus Partial Responses plus stable disease at 24 weeks on treatment

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate the Safety and Antitumor Activity of CX-2009 Monotherapy and in Combination With CX-072 in Advanced Breast Cancer
• Official Title: A Phase 2, Open-Label Study to Evaluate the Safety and Antitumor Activity of Praluzatamab Ravtansine (CX-2009) in Advanced HR-Positive/HER2-Negative Breast Cancer and of Praluzatamab Ravtansine as Monotherapy and in Combination With Pacmilimab (CX-072) in Advanced Triple-Negative Breast Cancer (CTMX-2009-002)
• Brief Summary: A Phase 2, clinical study in advanced, metastatic breast cancer that will evaluate CX-2009 monotherapy in both Hormone Receptor(HR) positive/HER2 negative breast cancer and in TNBC, and evaluate CX-2009+CX-072 in TNBC

Detailed Description

Eligible patients will be enrolled to the treatment arm based on breast cancer subtype.

Patients will receive study treatment on Day 1 of a Q3W cycle. Treatment with CX-2009 monotherapy (Arms A and B) or CX-2009 in combination with CX-072 (Arm C) will be given until disease progression or symptomatic deterioration, unacceptable toxicity necessitating treatment discontinuation, or if the patient meets certain study defined criteria for discontinuation. On-treatment tumor assessments, will occur every 6 weeks per RECIST v1.1 for the first 48 weeks, and every 12 weeks thereafter.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Neoplasms
• Breast Neoplasms
• Breast Neoplasms, Triple-Negative
• Breast Cancer
• Breast Neoplasms, Hormone Receptor Positive/HER2 Negative

Intervention

• Drug: CX-2009
  Intravenous administration of the CX-2009 of 6 mg/kg administered every 3 weeks (Q3W)
• Drug: CX-072
  Intravenous administration of the CX-072 of 1200 mg administered every 3 weeks (Q3W)

Study Arms

• Experimental: ARM A - CX-2009 Monotherapy, HR-positive/HER2-negative
  CX-2009 Monotherapy in advanced, metastatic Hormone Receptor (HR)-positive / Human Epidermal growth factor Receptor 2 (HER2)-negative breast cancer
  Intervention: Drug: CX-2009
• Experimental: ARM B - CX-2009 Monotherapy, TNBC
  CX-2009 Monotherapy in advanced, metastatic Triple-Negative Breast Cancer (TNBC)
  Intervention: Drug: CX-2009
• Experimental: ARM C - CX-2009 Combination therapy, TNBC
  CX-2009 and CX-072 Combination therapy in advanced, metastatic TNBC
  Interventions:

  • Drug: CX-2009
  • Drug: CX-072

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: August 5, 2022): 125
• Original Estimated Enrollment (submitted: October 15, 2020): 150
• Estimated Study Completion Date: April 30, 2023
• Estimated Primary Completion Date: April 30, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

INCLUSION CRITERIA:

• Arm A: inoperable, locally advanced or metastatic HR-positive/HER2-negative breast cancer. Patients must have received 0 to 2 prior cytotoxic chemotherapy in the inoperable, locally advanced, or metastatic setting
• Arm B and Arm C: inoperable, locally advanced or metastatic TNBC; archival or fresh tumor tissue must have high CD166 expression by immunohistochemistry (IHC). Patients must have received 1 - 3 prior lines of therapy for inoperable, locally advanced, or metastatic TNBC
• Arm C only: Patients must be Programmed Death Ligand 1 (PD-L1) positive by an FDA-approved test. For patients who have received prior checkpoint inhibitors (CPI) therapy: if the CPI was the most recent treatment given prior to enrollment into this study, the patient must not have progressed within 120 days of the first dose of the CPI
• Measurable disease per RECIST v1.1
• Adults, at least 18 years of age
• Eastern Cooperative Oncology Group performance status of 0 or 1
• Adequate baseline Laboratory Values
• Patients of childbearing potential or those with partners of childbearing potential must agree to use a highly effective method of birth control at least 1 month prior to first dose, during study treatment, and for a period of 50 days after the last dose of CX-2009 and 105 days after the last dose of CX-072 (Arm C).
• Patients with brain metastases that are ≤ 1 cm, are asymptomatic, and require no treatment may be eligible after discussion with Medical Monitor.
• Additional inclusion criteria may apply

EXCLUSION CRITERIA:

• History of malignancy that was active within the previous 2 years. Exceptions include localized cancers that are not related to the current cancer being treated, that are considered to have been cured, and in the opinion of the Investigator present a low risk for recurrence
• Untreated symptomatic brain and/or leptomeningeal metastases
• Unresolved prior therapy-related acute toxicity Grade > 1, including neuropathy. Alopecia and other nonacute toxicities are not exclusionary
• Active or chronic corneal disorder
• Serious concurrent illness
• History of allogeneic tissue/solid organ transplant, stem cell transplant, or bone marrow transplant

• Arm C only:

  • History of or current active autoimmune diseases
  • History of myocarditis regardless of the cause
  • History of intolerance to prior immune CPI therapy defined as the need to discontinue treatment due to an immune-related Adverse Event (AE)
  • Immunosuppressive therapy including chronic systemic steroid (≥ 10 mg daily prednisone equivalents) within 14 days of Cycle 1 Day 1 (C1D1). However, patients who require brief courses of steroids (eg, as prophylaxis for IV contrast or for treatment of an allergic reaction) may be eligible with Medical Monitor approval. Inhaled or topical steroids are permitted.
• History of severe allergic or anaphylactic reactions to previous monoclonal antibody (mAb) therapy or known hypersensitivity to any component of Probody therapeutic
• Prior treatment with maytansinoid-containing drug conjugates (eg, DM1 or DM4 antibody drug conjugate, including trastuzumab emtansine)
• Pregnant or breastfeeding
• Additional exclusion criteria may apply

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Korea, Republic of, Spain, United States

Administrative Information

• NCT Number: NCT04596150
• Other Study ID Numbers: CTMX-2009-002; 2020-004618-36 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: CytomX Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: CytomX Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Monika Vainorius, M.D.; CytomX Therapeutics

• PRS Account: CytomX Therapeutics
• Verification Date: March 2022