A Phase II, 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 Identifier:
CTMX-2009-002
CT.gov Identifier:
NCT04596150
EudraCT Identifier:
202101000000
EU Trial (CTIS) Number:
N/A
Study Contact Information:
(210) 593-5651 or [email protected]
Terminated/Withdrawn

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Study Summary

To evaluate CX-072 in combination with CX-2009 in patients with triple negative breast cancer (TNBC).

To 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

To investigate the safety and activity of CX-2009 monotherapy (7 mg/kg Q3W) and the combination of CX-2009 (7 mg/kg Q3W) + CX-072 (1200 mg Q3W) in patients with previously treated locally advanced or metastatic HER2- BC

To evaluate tolerability, pharmacokinetics, and antidrug antibodies with CX-2009 as monotherapy and in combination with CX-072.

Radiology assessments will be done Q6W.

This study will also evaluate safety and tolerability, pharmacokinetics, and antidrug antibodies with praluzatamab ravtansine as monotherapy and in combination with pacmilimab.

To evaluate the antitumor activity and characterize the safety and pharmacokinetics profiles of praluzatamab ravtansine, as monotherapy and in combination with pacmilimab, in patients with HER2-non-amplified breast cancer.

To evaluates CX-2009 as monotherapy in patients with advanced HR+/HER2− BC (Arm A) and TNBC (Arm B), and in combination with pacmilimab (a

conditionally activated PD-L1) in TNBC (Arm C)

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Breast Cancers
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    II
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Experimental: ARM A - CX-2009 Monotherapy, HR-positive/HER2-negative
    • Read More
  • Drug: Experimental: ARM B - CX-2009 Monotherapy, TNBC
  • Drug: Intervention/treatment
  • Drug: Experimental: ARM C - CX-2009 Combination therapy, TNBC
  • Drug: Drug: CX-072
  • Drug: Eligible patients will be enrolled to the treatment arm based on breast cancer subtype.
  • Drug: 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.
  • Drug: Arm A
  • Drug: All treatments will be given until disease progression or unacceptable toxicity.
  • Drug: ESMO Breast Cancer 2021:
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Terminated/Withdrawn

    Requirements information
    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 < or = 1 cm, are asymptomatic, and require treatment may be eligible after discussion with Medical Monitor.
    • Additional inclusion criteria may apply
    • 2-4 prior regimens (not including single-agent hormonal therapy)
    • Key eligibility criteria for the mHR+/HER2- BC cohort include 2–4 prior regimens in the metastatic setting (excluding single-agent endocrine therapy). No CD166 screening required for HR+/HER2- BC but mTNBC must be CD166+
    • Key eligibility criteria for all cohorts include: ECOG 0-1, acceptable end-organ function, measurable disease, willingness to receive ocular prophylaxis for DM-4 related toxicity, and available tumor tissue for CD166 evaluation. Eligibility criteria for HR+ BC include: 2-4 prior regimens (excluding single-agent hormonal therapy with up to 2 prior cytotoxic regimens) and a prior CDK 4/6 inhibitor in the metastatic setting; eligibility criteria for TNBC include CD166 by IHC >1% by central assessment, 1-3 prior regimens in the metastatic setting and prior taxane.
    • HR-positive/HER2-negative breast cancer
    • 1. Must have inoperable, locally advanced or metastatic HR-positive/HER2-negative breast cancer
    • 2. Histologically confirmed HR-positive/HER2-negative breast cancer based on the most recent analyzed biopsy defined as
    • 3. ER/PgR > 10%
    • 4. HER2 negative: IHC 0 or 1+ or HER2/CEP17 ratio 2.0 and average
    • HER2 copy number < 4.0 signals/cell by ISH
    • 5. Must have received at least 2 but no more than 4 prior systemic lines of treatment regimens for inoperable, locally advanced, or metastatic breast cancer (not including single-agent hormonal therapy).
    • 6. At least 1 cyclin-dependent kinase inhibitor 4/6 in any setting is
    • required.
    • 7. 0 to 2 prior cytotoxic chemotherapy in the inoperable, locally
    • advanced, or metastatic setting (eg, microtubulin-targeted agents,
    • including taxanes, antimetabolites, anthracyclines, alkylating agents,
    • topoisomerase 1 or 2 inhibitor)
    • 8. Patients with brain metastases that are ≤ 1 cm, are asymptomatic,
    • and require treatment may be eligible after discussion with Medical
    • Monitor.
    • 9. Patients with central nervous system lesions that are equivocal (ie,
    • may or may not be brain metastases) as assessed by the Investigator
    • may be enrolled without definitive local treatment.
    • TNBC
    • 10. Must have inoperable, locally advanced, or metastatic TNBC
    • 11. Histologically confirmed TNBC based on the most recent analyzed biopsy as defined in the protocol.
    • 12. Archival or fresh tumor tissue must have high CD166 expression by
    • IHC.
    • 13. Must have received at least 1 but no more than 3 prior systemic lines of treatment regimens for inoperable, locally advanced, or metastatic TNBC
    • 14. Prior receipt of a taxane (paclitaxel or docetaxel)-based regimen in
    • any setting (neoadjuvant, adjuvant, localized, or advanced/metastatic
    • disease) is required.
    • 15. If a patient has disease progression within 12 months following
    • completion of adjuvant therapy, the adjuvant therapy will count toward the number of treatments required for eligibility.
    • 16. Patients with known germline BRCA 1 or 2 mutations must have
    • received a platinum or poly ADP ribose polymerase (PARP) inhibitor.
    • 17. Arm B only: Patients whose tumors test positive for PD-L1 by an
    • approved test may enroll to Arm B only if they cannot be (re)treated
    • with a checkpoint inhibitor (CPI) for safety reasons (e.g., underlying
    • autoimmune disease, prior CPI treatment caused Grade 3 or 4 irAE
    • requiring permanent discontinuation)
    • 18. Arm C only: 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.
    • 19. Patients must have tumor tissue known to be positive for PD-L1
    • expression.
    • 20. Patients with brain metastases that are ≤ 1 cm, are asymptomatic, and require treatment may be eligible after discussion with Medical Monitor.
    • 21. Arms B and C: Patients with brain and/or leptomeningeal metastases are eligible if they have received standard-of-care treatment and are determined to be radiologically and clinically stable (ie, 2 scans at least 28 days apart, including the scan obtained during the screening period) and must not require radiation therapy or corticosteroids within 2 weeks prior to C1D1.
    • 22. Patients with central nervous system lesions that are equivocal (ie, may or may not be brain metastases) as assessed by the Investigator may be enrolled without definitive local treatment.
    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
    • For mTNBC patients who receive the doublet, key exclusion criteria include known PD-L1-negative tumor status, and progression within 120 days of first dose of an IO agent
    • key exclusion criteria include known PDL1 negative tumor, history of autoimmune disease, and progression within 120 days of 1st dose of an immuno-oncology agent. Pts with corneal disorders will be excluded.
    • Patients of childbearing potential should not get pregnant or breastfeed for 50 days for CX 2009 and 105 days for CX-072 after the last dose of study drug.

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (CIOCC)
    Madrid, Spain, 28050
    Investigator
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Breast Cancers