We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

XmAb®20717 Alone or in Combination With Chemotherapy or Targeted Therapy in Patients With Metastatic Castration-Resistant Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05005728
Recruitment Status : Recruiting
First Posted : August 13, 2021
Last Update Posted : May 26, 2022
Sponsor:
Information provided by (Responsible Party):
Xencor, Inc.

Brief Summary:
This Phase 2 study will investigate the safety and clinical activity of XmAb20717 alone or in combination with standard of care anticancer therapies in patients with metastatic castration-resistant prostate cancer (mCRPC) who have been treated with at least 2 prior lines of anticancer therapy.

Condition or disease Intervention/treatment Phase
Metastatic Castration-Resistant Prostate Cancer Combination Product: XmAb20717 + carboplatin + cabazitaxel Combination Product: XmAb20717 + olaparib Biological: XmAb20717 monotherapy Phase 2

Detailed Description:

Detailed Description:

This is a Phase 2, open-label, multiple-dose, multiple-arm, parallel assignment study in patients with mCRPC who have progressed after treatment with at least 2 prior lines of anticancer therapy. It will enroll subjects into one of 5 molecularly defined cohorts based on the results of acceptable, documented prior diagnostic testing:

  • Cohort A: Aggressive variant (anaplastic) adenocarcinoma of the prostate (AVPCa)
  • Cohort B: Homologous recombination deficient (HRD)/cyclin-dependent kinase 12 (CDK12) mutation positive tumors that have progressed on poly-adenosine diphosphate ribose polymerase inhibitors (HRD/CDK12 PARP Progressors)
  • Cohort C: HRD/CDK12 mutation positive tumors not previously treated with PARP inhibitors (HRD/CDK12 PARP Naïve)
  • Cohort D: Microsatellite instability-high (MSI-H) or mismatch repair deficient (MMRD) tumors (MSI-H/MMRD)
  • Cohort E: No Targetable Mutations

Subjects will receive XmAb20717 alone (Cohort D) or in combination with standard therapy (XmAb20717 + carboplatin + cabazitaxel [or docetaxel if no prior treatment]: Cohorts A, B, and E; XmAb20717 + olaparib: Cohort C).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 85 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2 Multiple-Dose, Multiple-Arm, Parallel Assignment Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of XmAb®20717 Alone or in Combination With Chemotherapy or Targeted Therapies in Selected Subjects With Metastatic Castration-Resistant Prostate Cancer
Actual Study Start Date : October 22, 2021
Estimated Primary Completion Date : June 30, 2023
Estimated Study Completion Date : June 30, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Cohort A - AVPCa
XmAb20717 + carboplatin + cabazitaxel
Combination Product: XmAb20717 + carboplatin + cabazitaxel
Subjects will receive XmAb20717 10 mg/kg IV every 2 weeks plus carboplatin target AUC 4 IV every 3 weeks and cabazitaxel 20 mg/m2 IV every 3 weeks

Experimental: Cohort B - HRD/CDK12 PARP - Progressors
XmAb20717 + carboplatin + cabazitaxel
Combination Product: XmAb20717 + carboplatin + cabazitaxel
Subjects will receive XmAb20717 10 mg/kg IV every 2 weeks plus carboplatin target AUC 4 IV every 3 weeks and cabazitaxel 20 mg/m2 IV every 3 weeks

Experimental: Cohort C - HRD/CDK12 PARP Naïve
XmAb20717 + olaparib
Combination Product: XmAb20717 + olaparib
Subjects will receive XmAb20717 10 mg/kg IV every 2 weeks plus olaparib 300 mg orally twice daily

Experimental: Cohort D - MSI-H or MMRD
XmAb20717 monotherapy
Biological: XmAb20717 monotherapy
Subjects will receive XmAb20717 10 mg/kg IV every 2 weeks

Experimental: Cohort E - No Targetable Mutations
XmAb20717 + carboplatin + cabazitaxel
Combination Product: XmAb20717 + carboplatin + cabazitaxel
Subjects will receive XmAb20717 10 mg/kg IV every 2 weeks plus carboplatin target AUC 4 IV every 3 weeks and cabazitaxel 20 mg/m2 IV every 3 weeks




Primary Outcome Measures :
  1. Incidence of treatment-emergent adverse events (safety and tolerability of XmAb20717) [ Time Frame: 8 weeks ]

Secondary Outcome Measures :
  1. Objective response rate (RECIST 1.1, as modified by PCWG3) [ Time Frame: 8 weeks ]
  2. Prostate-specific antigen (PSA) response [ Time Frame: 8 weeks ]
  3. Bone scans based on PCWG3 criteria [ Time Frame: 8 weeks ]
  4. Radiographic progression-free survival (PCWG3) [ Time Frame: 8 weeks ]
  5. Duration of response (RECIST 1.1, as modified by PCWG3) [ Time Frame: 8 weeks ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Able to provide written informed consent
  • Adult (age ≥ 18 years)
  • Histologically confirmed diagnosis of carcinoma of the prostate
  • Documented progressive mCRPC based on at least one of the following criteria:

    • PSA progression, defined as at least 2 rises in PSA with a minimum of a 1 week interval (1.0 ng/mL is the minimal starting value if confirmed rise is the only indication of progression)
    • Soft-tissue progression per RECIST 1.1
    • Progression of bone disease (evaluable disease) or 2 or more new bone lesions by bone scan
  • Progression after treatment with at least 2 prior lines of anticancer therapy approved for treatment of metastatic prostate cancer; prior treatment of subjects in Cohort D (MSI-H or MMRD) must include a checkpoint inhibitor approved by FDA for that indication
  • Subjects who did not have a surgical orchiectomy must be on androgen suppression treatment (eg, luteinizing hormone-releasing hormone agonist) with castrate level of testosterone (≤ 50 ng/dL) and be willing to continue the treatment throughout the study
  • Prior targeted or whole exome sequencing panel performed by CLIA-certified laboratory documenting:

    1. Cohort A (AVPCa) - Aggressive variant prostate cancer
    2. Cohort B or C (HRD) - Homologous recombination deficient (HRD) tumor
    3. Cohort D (MSI-H/MMRD) - Microsatellite instability-high (MSI-H) or mismatch repair deficient (MMRD) tumors (MSI-H/MMRD)
    4. Cohort E (No Targetable Mutations) - Not eligible for Cohorts A, B, C, or D
  • Evaluable disease according to PCWG3 criteria
  • Adequate archival metastatic tumor tissue or agree to undergo a biopsy of at least 1 metastatic site (fresh biopsy of primary prostate is only allowed if there is clear local disease and no other measurable disease site or biopsiable bone lesion)
  • ECOG performance status of 0 or 1
  • Able and willing to complete the study according to the study schedule

Exclusion Criteria:

Currently receiving anticancer therapies other than androgen deprivation therapy

  • Treatment with any other anticancer therapy within 2 weeks of the start of study drug (ie, other immunotherapy, chemotherapy, radiation therapy, etc.)
  • Prior treatment with any cytotoxic T-lymphocyte-associated protein (CTLA4), PD1, PDL1, or programmed cell death ligand 2 (PDL2) directed immunotherapy, except subjects in Cohort D, who will have had prior FDA-approved checkpoint inhibitor therapy
  • Grade 4 immune-mediated adverse events related to prior immunotherapy (applicable to subjects eligible for Cohort D)
  • Failure to recover from any toxicity related to previous anticancer treatment to ≤ Grade 2
  • Have known active central nervous system metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable, ie, are without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), are clinically stable, and are without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
  • Platelet count < 100 × 109/L
  • Hemoglobin level ≤ 9.0 g/dL
  • Absolute neutrophil count ≤ 1.7 × 109 for subjects who will receive cabazitaxel; < 1.0 × 109/L for all others
  • Aspartate aminotransferase at screening > 3 × upper limit of normal (ULN) for subjects without known liver involvement by tumor or > 5 × ULN for subjects with known liver involvement by tumor
  • Alanine aminotransferase at screening > 3 × ULN for subjects without known liver involvement by tumor or > 5 × ULN for subjects with known liver involvement by tumor
  • Bilirubin ≥ 1.5 × ULN (unless prior diagnosis and documentation of ongoing hemolysis or Gilbert's syndrome has been made)
  • Estimated creatinine clearance < 50 mL/minute calculated by the Cockcroft Gault or Modification of Diet in Renal Disease formulas
  • Active known or suspected autoimmune disease (except vitiligo; type 1 diabetes mellitus or residual hypothyroidism due to an autoimmune condition that is treatable with hormone replacement therapy only; psoriasis, atopic dermatitis, or another autoimmune skin condition that is managed without systemic therapy; or arthritis that is managed without systemic therapy beyond oral acetaminophen and nonsteroidal anti-inflammatory drugs)
  • Have any condition requiring systemic treatment with corticosteroids, prednisone equivalents, or other immunosuppressive medications within 14 days prior to first dose of study drug (except inhaled or topical corticosteroids or brief courses of corticosteroids given for prophylaxis of contrast dye allergic response). Subjects who are currently taking prednisone from a previous prostate cancer therapy will be permitted to enroll in the study.
  • Receipt of an organ allograft
  • Known history of left ventricular ejection fraction ≤ 40%
  • History or evidence of any other clinically unstable/uncontrolled disorder, condition, or disease other than their primary malignancy that, in the opinion of the Investigator, would pose a risk to patient safety or interfere with study evaluations, procedures, or completion
  • Evidence of any serious bacterial, viral, parasitic, or systemic fungal infections within the 30 days prior to the first dose of study drug
  • Receipt of a live-virus vaccine within 30 days prior to the first dose of study drug (seasonal flu vaccines that do not contain live virus are permitted)
  • A human immunodeficiency virus (HIV) positive subject with CD4+ T-cell (CD4+) counts < 350 cells/μL, or an HIV viral load greater than 400 copies/mL, or a history of an AIDS (acquired immunodeficiency syndrome)-defining opportunistic infection within the past 12 months, or who has not been on established antiretroviral therapy (ART) for at least 4 weeks prior to initiation of study drug dosing. (Effective ART is defined as a drug, dosage, and schedule associated with reduction and control of the viral load.)
  • Positive test for hepatitis C RNA (a subject who is hepatitis C virus [HCV] antibody positive but HCV RNA negative due to documented, curative prior antiviral treatment or natural resolution is eligible)
  • Positive test for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb; a subject whose HBsAg is negative and HBcAb is positive may be enrolled if a hepatitis B virus [HBV] DNA test is negative and the subject is retested for HBsAg and HBV DNA every 2 months)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05005728


Contacts
Layout table for location contacts
Contact: Jolene Shorr 858-275-0004 jshorr@xencor.com
Contact: Jennifer Ely 858-260-0464 jely@xencor.com

Locations
Layout table for location information
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
United States, Iowa
University of Iowa Hospitals & Clinics Recruiting
Iowa City, Iowa, United States, 52242
United States, Nebraska
GU Research Network/Urology Cancer Center Recruiting
Omaha, Nebraska, United States, 68130
United States, Nevada
Comprehensive Cancer Centers of Nevada Recruiting
Las Vegas, Nevada, United States, 89148
United States, New Mexico
XCancer New Mexico Oncology Hematology Consultants, Ltd. Recruiting
Albuquerque, New Mexico, United States, 87109
United States, New York
Montefiore Medical Center Recruiting
Bronx, New York, United States, 10461
Columbia University Recruiting
New York, New York, United States, 10032
United States, Pennsylvania
University of Pannsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
UPMC Hillman Cancer Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
United States, Washington
University of Washington/Seattle Cancer Care/Alliance Recruiting
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Xencor, Inc.
Investigators
Layout table for investigator information
Study Director: Jolene Shorr Xencor, Inc.
Layout table for additonal information
Responsible Party: Xencor, Inc.
ClinicalTrials.gov Identifier: NCT05005728    
Other Study ID Numbers: XmAb20717-04
First Posted: August 13, 2021    Key Record Dates
Last Update Posted: May 26, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Xencor, Inc.:
Prostate cancer
Metastatic castration resistant
Aggressive variant
Anaplastic
Neuroendocrine
Homologous recombination deficiency
MSI-H
CDK12
Additional relevant MeSH terms:
Layout table for MeSH terms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Carboplatin
Olaparib
Antineoplastic Agents
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action