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

Breast Cancer Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04596150
• Other study ID #: CTMX-2009-002
• Secondary ID: 2020-004618-36
• Status: Completed
• Phase: Phase 2
• Start date: December 29, 2020
• Est. completion date: June 2, 2023

Study information

• Verified date: January 2024
• Source: CytomX Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 125
• Est. completion date: June 2, 2023
• Est. primary completion date: June 2, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

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

Locations

Country	Name	City	State
Korea, Republic of	Soon Chun Hyang University Cheonan Hospital SCHMC	Cheonan
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Gangnam Severance Hospital	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona
Spain	Institut Catala Oncologia	Barcelona
Spain	Vall d'Hebron University Hospital	Barcelona
Spain	Hospital Universitario HM Sanchinarro	Madrid
Spain	Hospital Universitario Ramn y Cajal	Madrid
Spain	NEXT Oncology	Madrid
Spain	Hospital Parc Tauli	Sabadell
Spain	Hospital Clinico Universitario de Valencia	Valencia
United States	University of Maryland	Baltimore	Maryland
United States	Hematology Oncology Clinic	Baton Rouge	Louisiana
United States	DRCI	Boston	Massachusetts
United States	MGH	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	MUSC	Charleston	South Carolina
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	FCS - South	Fort Myers	Florida
United States	Indiana University Health Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Baptist Medical Center	Jacksonville	Florida
United States	Moores Cancer Center	La Jolla	California
United States	Rocky Mountain Cancer Centers	Lone Tree	Colorado
United States	Los Angeles Hematology Oncology Medical	Los Angeles	California
United States	USC Norris Cancer Center	Los Angeles	California
United States	University of Wisconsin	Madison	Wisconsin
United States	Allina Health System	Minneapolis	Minnesota
United States	Tennessee Oncology	Nashville	Tennessee
United States	Nebraska Cancer Specialists	Omaha	Nebraska
United States	UPMC Magee-Womens Hospital	Pittsburgh	Pennsylvania
United States	Hematology Oncology Assoc of the Treasure Coast	Port Saint Lucie	Florida
United States	FCS - North	Saint Petersburg	Florida
United States	Huntsman Cancer Institute Research	Salt Lake City	Utah
United States	UCLA David Geffen	Santa Monica	California
United States	Summit Cancer Centers	Spokane	Washington
United States	UT Health East Texas HOPE Cancer Center	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
CytomX Therapeutics

Countries where clinical trial is conducted

United States,  Korea, Republic of,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Overall Survival (OS)	The time from treatment initiation until death as a result of any cause	30 Months
Secondary	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
Secondary	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