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

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)

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

Study Overview

• Status: Completed
• Conditions: Neoplasms; Breast Cancer; Breast Neoplasms; Breast Neoplasms, Triple-Negative; Breast Neoplasms, Hormone Receptor Positive/HER2 Negative
• Intervention / Treatment: Drug: CX-2009; Drug: CX-072

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
• Enrollment (Actual): 125
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Cheonan, Korea, Republic of
    • Soon Chun Hyang University Cheonan Hospital SCHMC
  • Incheon, Korea, Republic of, 21565
    • Gachon University Gil Medical Center
  • Seongnam-si, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 02841
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 06273
    • Gangnam Severance Hospital
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial de Barcelona
  • Barcelona, Spain, 08036
    • Vall d'Hebron University Hospital
  • Barcelona, Spain, 08908
    • Institut Catala Oncologia
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro
  • Madrid, Spain, 28034
    • Hospital Universitario Ramn y Cajal
  • Madrid, Spain, 28050
    • NEXT Oncology
  • Sabadell, Spain, 08208
    • Hospital Parc Tauli
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
• United States
  • California
    • La Jolla, California, United States, 92093
      • Moores Cancer Center
    • Los Angeles, California, United States, 90033
      • USC Norris Cancer Center
    • Los Angeles, California, United States, 90017
      • Los Angeles Hematology Oncology Medical
    • Santa Monica, California, United States, 90404
      • UCLA David Geffen
  • Colorado
    • Lone Tree, Colorado, United States, 80124
      • Rocky Mountain Cancer Centers
  • Florida
    • Fort Myers, Florida, United States, 33901
      • FCS - South
    • Jacksonville, Florida, United States, 32207
      • Baptist Medical Center
    • Port Saint Lucie, Florida, United States, 34952
      • Hematology Oncology Assoc of the Treasure Coast
    • Saint Petersburg, Florida, United States, 33705
      • FCS - North
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health Melvin and Bren Simon Cancer Center
  • Louisiana
    • Baton Rouge, Louisiana, United States, 78809
      • Hematology Oncology Clinic
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • MGH
    • Boston, Massachusetts, United States, 02215
      • DRCI
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Allina Health System
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Nebraska Cancer Specialists
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Magee-Womens Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • MUSC
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology
  • Texas
    • Tyler, Texas, United States, 75701
      • UT Health East Texas Hope Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute Research
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists
  • Washington
    • Spokane, Washington, United States, 99208
      • Summit Cancer Centers
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	Drug: CX-2009; Intravenous administration of the CX-2009 of 6 mg/kg administered every 3 weeks (Q3W)
Experimental: ARM B - CX-2009 Monotherapy, TNBC; CX-2009 Monotherapy in advanced, metastatic Triple-Negative Breast Cancer (TNBC)	Drug: CX-2009; Intravenous administration of the CX-2009 of 6 mg/kg administered every 3 weeks (Q3W)
Experimental: ARM C - CX-2009 Combination therapy, TNBC; CX-2009 and CX-072 Combination therapy in advanced, metastatic TNBC	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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	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)	30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigator-assessed Progression-Free Survival (PFS)	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	30 Months
Duration of Response (DoR)	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)	30 Months
Overall Survival (OS)	The time from treatment initiation until death as a result of any cause	30 Months
Clinical Benefit Rate (CBR) at 16 Weeks	This will include sum of confirmed Complete plus Partial Responses plus stable disease at 16 weeks on treatment	30 Months
Clinical Benefit Rate (CBR) at 24 Weeks	This will include sum of confirmed Complete plus Partial Responses plus stable disease at 24 weeks on treatment	30 Months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): December 29, 2020
• Primary Completion (Actual): June 2, 2023
• Study Completion (Actual): June 2, 2023

Study Registration Dates

• First Submitted: October 2, 2020
• First Submitted That Met QC Criteria: October 15, 2020
• First Posted (Actual): October 22, 2020

Study Record Updates

• Last Update Posted (Estimated): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Breast cancer; PD-L1; HR+; Triple negative breast cancer; Hormone Receptor; Hormone Receptor Positive; CD166; HR-positive/HER2-non-amplified; HER2 non-amplified; N2'-deacetyl-N2'-(4-mercapto-4-methyl-1-oxopentyl)-maytansine (DM4); Cluster of Differentiation 166 (CD166); Probody; Armed antibody; Mytansine; DM4; Praluzatamab Ravtansine; Pacmilimab
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Site; Breast Diseases; Neoplasms; Breast Neoplasms; Triple Negative Breast Neoplasms
• Other Study ID Numbers: CTMX-2009-002; 2020-004618-36 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No