A Study of XmAb20717 (Vudalimab)in Patients With Selected Advanced Gynecologic and Genitourinary Malignancies
Primary Purpose
Ovarian Cancer, Clear Cell Carcinoma, Endometrial Cancer
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
vudalimab
Sponsored by
About this trial
This is an interventional treatment trial for Ovarian Cancer focused on measuring Endometrial Cancer, Ovarian Cancer, Cervical Cancer, Prostate Cancer, Gynecological Cancer,, Fallopian Tube Cancer, Peritoneal Cancer, Clear Cell Carcinoma, vudalimab, XmAb20717
Eligibility Criteria
Inclusion Criteria:
- Able to provide written informed consent
- Adult (age ≥ 18 years)
- Cancer must have progressed after treatment with all approved and medically appropriate therapies or have no appropriate available therapies
Histologically confirmed diagnosis of one of the following tumor types, along with clinical/pathologic confirmation of the additional requirements for each indication, as appropriate:
- Persistent or recurrent clear cell carcinoma of the ovary, peritoneum, or endometrium after treatment with platinum-based systemic chemotherapy
- Persistent or recurrent high-grade serous carcinoma of the ovary, fallopian tube, or peritoneum after treatment with platinum-based systemic chemotherapy (except subjects with a diagnosis of carcinosarcoma)
- Recurrent or metastatic cervical carcinoma previously treated with standard-of-care systemic chemotherapy and FDA-approved immunotherapy, if eligible
- Advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) in patients who are not candidates for curative surgery or radiation, and that has progressed following treatment with no more than one prior line of systemic therapy and prior treatment with FDA-approved combination therapy consisting of a checkpoint inhibitor and a targeted agent
High-risk metastatic castration-resistant prostate cancer:
- Castration resistance defined as progressive disease after surgical castration, or progression in the setting of medical androgen ablation with a castrate level of testosterone (< 50 ng/dL)
- High-risk disease is any visceral, soft tissue, or lymph node metastasis(es) with/without bone metastases
- Measurable disease by Response Evaluation Criteria in Solid Tumours (RECIST 1.1)
- Adequate available archival formalin-fixed paraffin-embedded block(s)/slides containing tumor and/or adequate predose fresh tumor biopsy tissue
- Eastern Cooperative Oncology Group performance status of 0 or 1
- Female subjects of childbearing potential must agree to use a highly effective method of birth control during and for 4 weeks after completion of study. Women are considered to be of childbearing potential unless it is documented that they are over the age of 60 OR postmenopausal by history with no menses for 1 year and confirmed by follicle-stimulating hormone (using local reference ranges) OR have a history of hysterectomy and/or bilateral oophorectomy OR have a history of bilateral tubal ligation. Highly effective methods of birth control include hormonal birth control (oral, intravaginal, or transdermal), or progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or intrauterine), intrauterine devices (IUDs), intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner (provided partner is the sole sexual partner and there has been a medical assessment of surgical success), or sexual abstinence
- Fertile male subjects must be willing to practice a highly effective method of birth control during and for 4 weeks after completion of study
- Male subjects must agree not to donate sperm from screening through 4 weeks after completion of study
- Able and willing to complete the entire study according to the study schedule
Exclusion Criteria:
- - Subjects currently receiving other anticancer therapies, except that subjects with prostate cancer may continue to receive luteinizing hormone-releasing hormone (LHRH) analogue therapy
- More than 2 prior chemotherapy regimens for subjects in the cervical cancer, CCC, HGSOC, or prostate cancer cohorts
- Prior treatment with a CTLA4-targeted agent
Prior treatment with nivolumab, pembrolizumab, or any other PD1-, PDL1- or programmed cell death ligand 2- (PDL2)-directed therapy, except that:
- Subjects with MSS EC may have received anti-PD1 therapy as part of an FDA-approved regimen in the approved disease setting
- Subjects with cervical cancer may have received anti-PD1 therapy as an FDA-approved agent in the approved disease setting
- Treatment with any other anticancer therapy within 2 weeks of the start of study drug (ie, other immunotherapy, chemotherapy, radiation therapy, etc.)
- A life-threatening (Grade 4) immune-mediated adverse event (AE) associated with prior administration of an immunotherapy agent
- Failure to recover from any immunotherapy-related toxicity from prior cancer therapy to ≤ Grade 1, except that subjects are eligible if a previous immunotherapy-related endocrinopathy is medically managed with hormone replacement therapy only
- Failure to recover from any other cancer therapy-related toxicity (other than immune-related toxicity) related to previous anticancer treatment to ≤ Grade 2
- Have known active central nervous system metastases and/or carcinomatous meningitis
- Platelet count < 100 × 109/L
- Hemoglobin level ≤ 9.0 g/dL
- Absolute neutrophil count < 1.5 × 109/L
- Aspartate aminotransferase (AST) 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 (ALT) 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 that subjects are permitted to enroll if they have vitiligo; type 1 diabetes mellitus or residual hypothyroidism due to an autoimmune condition that is treatable with hormone replacement therapy only; autoimmune adrenal insufficiency that is managed with low-dose corticosteroids; 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)
- • Has any condition requiring systemic treatment with corticosteroids, prednisone equivalents, or other immunosuppressive medications within 14 days prior to first dose of study drug (except that inhaled or topical corticosteroids or brief courses of corticosteroids given for prophylaxis of contrast dye allergic response are permitted)
- Receipt of an organ allograft
- History of small or large bowel obstruction within 3 months of enrollment, including subjects with palliative gastric drainage catheters. Subjects with palliative diverting ileostomy or colostomy are allowed if they have been symptom-free for more than 3 months.
- Ongoing bowel perforation or presence of bowel fistula or intra-abdominal abscess
- Subjects with refractory ascites, for example, ascites needing drainage catheter or therapeutic paracentesis more often than every 4 weeks
- Histologic diagnosis of carcinosarcoma of the ovary
- Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression
- History or evidence of any other clinically unstable/uncontrolled disorder, condition, or disease (including, but not limited to, cardiopulmonary, renal, metabolic, hematologic, or psychiatric) 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 first dose of study drug (seasonal flu and COVID-19 vaccines are permitted, as long as they do not contain live virus and are not administered within 24 hours of planned administration of XmAb20717)
- An 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 acquired immunodeficiency syndrome (AIDS)-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. HIV positive subjects who do not meet any of these exclusion criteria are eligible.)
- 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. (See the protocol for treatment requirements for subjects with HBV who become HBsAg and HBV DNA positive during the study.)
- Subject is pregnant or breastfeeding or planning to become pregnant while enrolled in the study, up to the final end-of-treatment visit
- Positive urine pregnancy test (ie, urine human chorionic gonadotropin)
Sites / Locations
- UCSD Moores Cancer CenterRecruiting
- Valkyrie Clinical TrialsRecruiting
- UCLA Medical CenterRecruiting
- Kaiser Permanente Medical GroupRecruiting
- UCSF Helen Diller Family Comprehensive Cancer CenterRecruiting
- Moffitt Cancer CenterRecruiting
- Winship Cancer Institute, Emory UniversityRecruiting
- Karmanos Cancer InstituteRecruiting
- Comprehensive Cancer Centers of Nevada-Southern HillsRecruiting
- NYU Langone HealthRecruiting
- Columbia University Medical CenterRecruiting
- University of Pennsylvania Health SystemRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
vudalimab
Arm Description
Outcomes
Primary Outcome Measures
ORR as assessed by RECIST 1.1 criteria (efficacy)
To determine the Objective Response Rate as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Secondary Outcome Measures
Full Information
NCT ID
NCT05032040
First Posted
August 31, 2021
Last Updated
October 10, 2023
Sponsor
Xencor, Inc.
Collaborators
ICON plc
1. Study Identification
Unique Protocol Identification Number
NCT05032040
Brief Title
A Study of XmAb20717 (Vudalimab)in Patients With Selected Advanced Gynecologic and Genitourinary Malignancies
Official Title
A Phase 2 Study of XmAb20717 in Patients With Selected Gynecological Malignancies and High-Risk Metastatic Castration-Resistant Prostate Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 21, 2022 (Actual)
Primary Completion Date
March 15, 2025 (Anticipated)
Study Completion Date
May 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Xencor, Inc.
Collaborators
ICON plc
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a Phase 2, multicenter, two-stage, open-label, parallel-group study designed to evaluate the efficacy and safety of vudalimab (XmAb20717) in patients with selected advanced gynecologic and genitourinary malignancies.
Detailed Description
This is a Phase 2, multicenter, two-stage, open-label, parallel-group study designed to evaluate the efficacy and safety of vudalimab in patients with selected advanced gynecologic and genitourinary malignancies and to identify tumor types for further evaluation.
In Stage 1, subjects will be enrolled into 1 of 5 tumor-specific, parallel cohorts (n = 10 each):
Platinum-resistant high-grade serous ovarian cancer (HGSOC)
Chemotherapy relapsed or refractory clear cell ovarian, endometrial, or peritoneal cancer
Immune-checkpoint-inhibitor-refractory microsatellite stable (MSS) endometrial cancer (EC)
Previously treated recurrent or metastatic cervical cancer
High-risk metastatic castration-resistant prostate cancer (mCRPC)
Within each tumor-specific cohort in Stage 1, a primary endpoint of ORR at 12 weeks, based on investigator review, will be used to determine cohort expansion into Stage 2. Each Stage 1 cohort that achieves an ORR of ≥ 20% (at least 2 out of 10 subjects with an objective response) will enroll up to an additional 20 subjects in Stage 2. Cohorts with an ORR of less than 20% will discontinue enrollment. However, additional factors will be considered in determining an expansion into Stage 2 (eg, enrollment rate, complete versus partial response, and DOR).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer, Clear Cell Carcinoma, Endometrial Cancer, Cervical Carcinoma, Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Keywords
Endometrial Cancer, Ovarian Cancer, Cervical Cancer, Prostate Cancer, Gynecological Cancer,, Fallopian Tube Cancer, Peritoneal Cancer, Clear Cell Carcinoma, vudalimab, XmAb20717
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
150 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
vudalimab
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
vudalimab
Intervention Description
Monoclonal bispecific antibody
Primary Outcome Measure Information:
Title
ORR as assessed by RECIST 1.1 criteria (efficacy)
Description
To determine the Objective Response Rate as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time Frame
12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Able to provide written informed consent
Adult (age ≥ 18 years)
Cancer must have progressed after treatment with all approved and medically appropriate therapies or have no appropriate available therapies
Histologically confirmed diagnosis of one of the following tumor types, along with clinical/pathologic confirmation of the additional requirements for each indication, as appropriate:
Persistent or recurrent clear cell carcinoma of the ovary, peritoneum, or endometrium after treatment with platinum-based systemic chemotherapy
Persistent or recurrent high-grade serous carcinoma of the ovary, fallopian tube, or peritoneum after treatment with platinum-based systemic chemotherapy (except subjects with a diagnosis of carcinosarcoma)
Recurrent or metastatic cervical carcinoma previously treated with standard-of-care systemic chemotherapy and FDA-approved immunotherapy, if eligible
Advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) in patients who are not candidates for curative surgery or radiation, and that has progressed following treatment with no more than one prior line of systemic therapy and prior treatment with FDA-approved combination therapy consisting of a checkpoint inhibitor and a targeted agent
High-risk metastatic castration-resistant prostate cancer:
Castration resistance defined as progressive disease after surgical castration, or progression in the setting of medical androgen ablation with a castrate level of testosterone (< 50 ng/dL)
High-risk disease is any visceral, soft tissue, or lymph node metastasis(es) with/without bone metastases
Measurable disease by Response Evaluation Criteria in Solid Tumours (RECIST 1.1)
Adequate available archival formalin-fixed paraffin-embedded block(s)/slides containing tumor and/or adequate predose fresh tumor biopsy tissue
Eastern Cooperative Oncology Group performance status of 0 or 1
Female subjects of childbearing potential must agree to use a highly effective method of birth control during and for 4 weeks after completion of study. Women are considered to be of childbearing potential unless it is documented that they are over the age of 60 OR postmenopausal by history with no menses for 1 year and confirmed by follicle-stimulating hormone (using local reference ranges) OR have a history of hysterectomy and/or bilateral oophorectomy OR have a history of bilateral tubal ligation. Highly effective methods of birth control include hormonal birth control (oral, intravaginal, or transdermal), or progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or intrauterine), intrauterine devices (IUDs), intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner (provided partner is the sole sexual partner and there has been a medical assessment of surgical success), or sexual abstinence
Fertile male subjects must be willing to practice a highly effective method of birth control during and for 4 weeks after completion of study
Male subjects must agree not to donate sperm from screening through 4 weeks after completion of study
Able and willing to complete the entire study according to the study schedule
Exclusion Criteria:
- Subjects currently receiving other anticancer therapies, except that subjects with prostate cancer may continue to receive luteinizing hormone-releasing hormone (LHRH) analogue therapy
More than 2 prior chemotherapy regimens for subjects in the cervical cancer, CCC, HGSOC, or prostate cancer cohorts
Prior treatment with a CTLA4-targeted agent
Prior treatment with nivolumab, pembrolizumab, or any other PD1-, PDL1- or programmed cell death ligand 2- (PDL2)-directed therapy, except that:
Subjects with MSS EC may have received anti-PD1 therapy as part of an FDA-approved regimen in the approved disease setting
Subjects with cervical cancer may have received anti-PD1 therapy as an FDA-approved agent in the approved disease setting
Treatment with any other anticancer therapy within 2 weeks of the start of study drug (ie, other immunotherapy, chemotherapy, radiation therapy, etc.)
A life-threatening (Grade 4) immune-mediated adverse event (AE) associated with prior administration of an immunotherapy agent
Failure to recover from any immunotherapy-related toxicity from prior cancer therapy to ≤ Grade 1, except that subjects are eligible if a previous immunotherapy-related endocrinopathy is medically managed with hormone replacement therapy only
Failure to recover from any other cancer therapy-related toxicity (other than immune-related toxicity) related to previous anticancer treatment to ≤ Grade 2
Have known active central nervous system metastases and/or carcinomatous meningitis
Platelet count < 100 × 109/L
Hemoglobin level ≤ 9.0 g/dL
Absolute neutrophil count < 1.5 × 109/L
Aspartate aminotransferase (AST) 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 (ALT) 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 that subjects are permitted to enroll if they have vitiligo; type 1 diabetes mellitus or residual hypothyroidism due to an autoimmune condition that is treatable with hormone replacement therapy only; autoimmune adrenal insufficiency that is managed with low-dose corticosteroids; 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)
• Has any condition requiring systemic treatment with corticosteroids, prednisone equivalents, or other immunosuppressive medications within 14 days prior to first dose of study drug (except that inhaled or topical corticosteroids or brief courses of corticosteroids given for prophylaxis of contrast dye allergic response are permitted)
Receipt of an organ allograft
History of small or large bowel obstruction within 3 months of enrollment, including subjects with palliative gastric drainage catheters. Subjects with palliative diverting ileostomy or colostomy are allowed if they have been symptom-free for more than 3 months.
Ongoing bowel perforation or presence of bowel fistula or intra-abdominal abscess
Subjects with refractory ascites, for example, ascites needing drainage catheter or therapeutic paracentesis more often than every 4 weeks
Histologic diagnosis of carcinosarcoma of the ovary
Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression
History or evidence of any other clinically unstable/uncontrolled disorder, condition, or disease (including, but not limited to, cardiopulmonary, renal, metabolic, hematologic, or psychiatric) 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 first dose of study drug (seasonal flu and COVID-19 vaccines are permitted, as long as they do not contain live virus and are not administered within 24 hours of planned administration of vudalimab
An 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 acquired immunodeficiency syndrome (AIDS)-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. HIV positive subjects who do not meet any of these exclusion criteria are eligible.)
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. (See the protocol for treatment requirements for subjects with HBV who become HBsAg and HBV DNA positive during the study.)
Subject is pregnant or breastfeeding or planning to become pregnant while enrolled in the study, up to the final end-of-treatment visit
Positive urine pregnancy test (ie, urine human chorionic gonadotropin)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nital Soni
Phone
858-500-6429
Email
nsoni@xencor.com
First Name & Middle Initial & Last Name or Official Title & Degree
Sarah Danowski
Email
sdanowski@xencor.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sandra Calman, MD
Organizational Affiliation
Xencor, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
UCSD Moores Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Individual Site Status
Recruiting
Facility Name
Valkyrie Clinical Trials
City
Los Angeles
State/Province
California
ZIP/Postal Code
90067
Country
United States
Individual Site Status
Recruiting
Facility Name
UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
92004
Country
United States
Individual Site Status
Recruiting
Facility Name
Kaiser Permanente Medical Group
City
Riverside
State/Province
California
ZIP/Postal Code
92505
Country
United States
Individual Site Status
Recruiting
Facility Name
UCSF Helen Diller Family Comprehensive Cancer Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Individual Site Status
Recruiting
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Individual Site Status
Recruiting
Facility Name
Winship Cancer Institute, Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Individual Site Status
Recruiting
Facility Name
Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Individual Site Status
Recruiting
Facility Name
Comprehensive Cancer Centers of Nevada-Southern Hills
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89148
Country
United States
Individual Site Status
Recruiting
Facility Name
NYU Langone Health
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Pennsylvania Health System
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study of XmAb20717 (Vudalimab)in Patients With Selected Advanced Gynecologic and Genitourinary Malignancies
We'll reach out to this number within 24 hrs