Clinical trial NCT03517488: A Study of XmAb®20717 in Subjects With Selected Advanced Solid Tumors
Official title: A Phase 1 Multiple Dose Study to Evaluate the Safety and Tolerability of XmAb®20717 in Subjects With Selected Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Melanoma
Breast Carcinoma
Hepatocellular Carcinoma
Urothelial Carcinoma
Squamous Cell Carcinoma of the Head and Neck
Renal Cell Carcinoma
Colorectal Carcinoma
Non-small Cell Lung Carcinoma
Gastric or Gastroesophageal Junction Adenocarcinoma
Endometrial Carcinoma
Mesothelioma
Neuroendocrine Carcinoma
Cervical Cancer
Small Cell Lung Carcinoma
Squamous Cell Carcinoma of the Anus
Castration-Resistant Prostate Carcinoma
Nasopharyngeal Carcinoma
Cholangiocarcinoma
Basal Cell Carcinoma
Ovarian Carcinoma
Fallopian Tube Carcinoma
Thymoma
Thymic Carcinoma
Squamous Cell Carcinoma of the Penis
Vulvar Carcinoma
Solid Tumors With Published Evidence of Anti-tumor Activity With Anti-PD1/PDL1 and/or Anti-CTLA4-directed Therapy
Malignant Adnexal Neoplasms
Non-squamous Cell Salivary Gland Carcinoma
Keywords: DUET-2
Melanoma
Triple Negative Breast Cancer
Hepatocellular Cancer
Urothelial Cancer
Renal Cell Cancer
Head and Neck Cancer
MSI-high Colorectal Cancer
MSI-high Endometrial Cancer
Non-small Cell Lung Cancer
Gastric Cancer
Gastroesophageal Junction Cancer
Mesothelioma
High-grade Neuroendocrine Cancer
Cervical Cancer
Small Cell Lung Cancer
Anal Cancer
Prostate Cancer
Nasopharyngeal Cancer
Bile Duct Cancer
Basal Cell Skin Cancer
Ovarian Cancer
Fallopian Tube Cancer
Malignant Adnexal Tumor
Thymus Cancer
Penile Cancer
Vulvar Cancer
Salivary Gland Cancer
Lead sponsor: Xencor, Inc.
Sponsor class: INDUSTRY
Collaborators: name: ICON plc
First posted: 2018-05-07
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a Phase 1, multiple dose, ascending dose escalation study to define a MTD/RD and regimen of XmAb20717, to describe safety and tolerability, to assess PK and immunogenicity, and to preliminarily assess anti-tumor activity of XmAb20717 in subjects with selected advanced solid tumors.


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed diagnosis of one of the following advanced solid tumors:

PART A (Dose Escalation Cohorts)

1. Melanoma;
2. Breast carcinoma that is estrogen receptor, progesterone receptor, and Her2 negative (triple-negative breast cancer; TNBC);
3. Hepatocellular carcinoma;
4. Urothelial carcinoma;
5. Squamous cell carcinoma of the head and neck;
6. Renal cell carcinoma (clear cell predominant type);
7. Microsatellite instability-high or mismatch repair deficient colorectal carcinoma or endometrial carcinoma;
8. Non-small cell lung carcinoma;
9. Gastric or gastroesophageal junction adenocarcinoma
10. Mesothelioma;
11. High-grade neuroendocrine carcinoma, including small cell carcinoma of the lung
12. Cervical cancer;
13. Squamous cell carcinoma of the anus

PART B (Dose Expansion Cohorts):

1. Melanoma
2. Renal cell carcinoma (clear cell predominant type)
3. Non-small cell lung carcinoma
4. Castrate-resistant adenocarcinoma of the prostate, 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)
5. Nasopharyngeal carcinoma
6. Cholangiocarcinoma
7. Basal cell carcinoma
8. Squamous cell carcinoma of the anus
9. Mesothelioma
10. Ovarian or fallopian tube carcinoma
11. Malignant adnexal neoplasms (including, but not limited to, sebaceous carcinoma, trichilemmal carcinoma, pilomatrix carcinoma, eccrine carcinoma, hidradenocarcinoma, adnexal carcinoma with divergent differentiation, papillary digital eccrine adenocarcinoma, microcystic adnexal carcinoma, and clear cell eccrine carcinoma)
12. Thymoma
13. Thymic carcinoma
14. Squamous cell carcinoma of the penis
15. Neuroendocrine carcinoma
16. Vulvar cancer
17. Non-squamous cell salivary gland carcinoma (except adenoid cystic carcinoma)
18. Subjects with other solid tumors for which there is published evidence of anti-tumor activity with anti-PD1/PDL1 and/or anti-CTLA4-directed therapy but for which there is no FDA-approved anti-PD1/PDL1 or CTLA4-directed checkpoint inhibitor treatment may be eligible for Part B after approval by the Medical Monitor.

    * All subjects' cancer must have progressed after treatment with all standard therapies or have no appropriate available therapies.
    * Subjects, except those with adenocarcinoma of the prostate, must have measurable disease by RECIST 1.1.
    * Have available adequate archival formalin-fixed paraffin-embedded block(s)/slides containing tumor or adequate pre-dose fresh tumor biopsy tissue
    * ECOG performance status of 0 - 1
    * Subjects with adenocarcinoma of the prostate must have evaluable disease (measurable or nonmeasurable lesions) by PCWG3.

Exclusion Criteria:

* Subjects currently receiving other anticancer therapies, with the exception of subjects with adenocarcinoma of the prostate, who may continue luteinizing hormone-releasing hormone (LHRH) analogue therapy.
* Treatment with any CTLA4 antibody within 6 weeks of the start of study drug.
* Treatment with nivolumab or any PDL1 or PDL2-directed antibody within 4 weeks of the start of study drug.
* Treatment with pembrolizumab within 4 - 12 weeks of the start of study drug (cohort dependent).
* Treatment with any other anticancer therapy within 2 weeks of the start of study drug (i.e., other immunotherapy, chemotherapy, radiation therapy, etc.). Subjects with prostate cancer may continue LHRH analogue therapy.
* A life-threatening (Grade 4) immune-mediated AE related to prior immunotherapy.
* Failure to recover from any immune-related toxicity from prior cancer therapy to ≤ Grade 1, except if previous immune-related endocrinopathy is medically managed with hormone replacement therapy only.
* Failure to recover from any other toxicity (other than immune-related toxicity) related to previous anticancer treatment to ≤ Grade 2.
* Have known active CNS metastases and/or carcinomatous meningitis. Participants 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, are clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
* 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; 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 non-steroidal 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.
* Prior treatment with any checkpoint inhibitor therapy regimen that targets both PD1/L1 and CTLA-4.

Primary outcomes:
measure: Determine the safety and tolerability profile of XmAb20717
timeFrame: 56 Days
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute
state: California
city: Los Angeles
country: United States
facility: UCLA Hematology-Oncology Clinic (Westwood)
state: California
city: San Diego
country: United States
facility: University of California San Diego Moores Cancer Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Medical Center
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medicine
state: Illinois
city: Fairway
country: United States
facility: The University of Kansas Clinical Research Center
state: Kansas
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center at NYU Langone
state: New York
city: New York
country: United States
facility: Columbia University Medical Center - Herbert Irving Pavilion
state: New York
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah, Huntsman Cancer Institute
state: Utah
city: Charlottesville
country: United States
facility: Emily Couric Clinical Cancer Center
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
Study officials:
affiliation: Xencor, Inc.
name: Zequn Tang, MD
role: STUDY_DIRECTOR
References: