Clinical trial NCT04596150: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neoplasms
Breast Neoplasms
Breast Neoplasms, Triple-Negative
Breast Cancer
Breast Neoplasms, Hormone Receptor Positive/HER2 Negative
Keywords: HR-positive/HER2-non-amplified
HR+
HER2 non-amplified
Hormone Receptor
N2'-deacetyl-N2'-(4-mercapto-4-methyl-1-oxopentyl)-maytansine (DM4)
Cluster of Differentiation 166 (CD166)
Triple negative breast cancer
Breast cancer
Probody
Armed antibody
Mytansine
Hormone Receptor Positive
DM4
CD166
PD-L1
Praluzatamab Ravtansine
Pacmilimab
Lead sponsor: CytomX Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-10-22
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 30 months
Secondary outcomes:
measure: Investigator-assessed Progression-Free Survival (PFS)
timeFrame: 30 Months
measure: Duration of Response (DoR)
timeFrame: 30 Months
measure: Overall Survival (OS)
timeFrame: 30 Months
measure: Clinical Benefit Rate (CBR) at 16 Weeks
timeFrame: 30 Months
measure: Clinical Benefit Rate (CBR) at 24 Weeks
timeFrame: 30 Months
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: Los Angeles Hematology Oncology Medical
state: California
city: Los Angeles
country: United States
facility: USC Norris Cancer Center
state: California
city: Santa Monica
country: United States
facility: UCLA David Geffen
state: California
city: Lone Tree
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Fort Myers
country: United States
facility: FCS - South
state: Florida
city: Jacksonville
country: United States
facility: Baptist Medical Center
state: Florida
city: Port Saint Lucie
country: United States
facility: Hematology Oncology Assoc of the Treasure Coast
state: Florida
city: Saint Petersburg
country: United States
facility: FCS - North
state: Florida
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Health Melvin and Bren Simon Cancer Center
state: Indiana
city: Baton Rouge
country: United States
facility: Hematology Oncology Clinic
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: MGH
state: Massachusetts
city: Boston
country: United States
facility: DRCI
state: Massachusetts
city: Minneapolis
country: United States
facility: Allina Health System
state: Minnesota
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Pittsburgh
country: United States
facility: UPMC Magee-Womens Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: MUSC
state: South Carolina
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Tyler
country: United States
facility: UT Health East Texas HOPE Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute Research
state: Utah
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Spokane
country: United States
facility: Summit Cancer Centers
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Cheonan
country: Korea, Republic of
facility: Soon Chun Hyang University Cheonan Hospital SCHMC
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
city: Barcelona
country: Spain
facility: Vall d'Hebron University Hospital
city: Barcelona
country: Spain
facility: Institut Catala Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario Ramn y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
city: Madrid
country: Spain
facility: NEXT Oncology
city: Sabadell
country: Spain
facility: Hospital Parc Tauli
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
Study officials:
affiliation: CytomX Therapeutics
name: Monika Vainorius, M.D.
role: STUDY_DIRECTOR
References: