DUET-2: A Study of XmAb®20717 in Subjects With Selected Advanced Solid Tumors

Sponsor

Xencor, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03517488

Collaborator

ICON plc (Industry)

154

Enrollment

Locations

Arm

52.7

Anticipated Duration (Months)

9.1

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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	Biological: XmAb20717	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

154 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1 Multiple Dose Study to Evaluate the Safety and Tolerability of XmAb®20717 in Subjects With Selected Advanced Solid Tumors

Actual Study Start Date :

Jul 10, 2018

Anticipated Primary Completion Date :

Nov 30, 2022

Anticipated Study Completion Date :

Nov 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: XmAb20717 XmAb20717 administered by intravenous dosing on Days 1 and 15 of each 28-day cycle for a total of two cycles	Biological: XmAb20717 Monoclonal bispecific antibody

Arm

Intervention/Treatment

Experimental: XmAb20717

XmAb20717 administered by intravenous dosing on Days 1 and 15 of each 28-day cycle for a total of two cycles

Biological: XmAb20717

Monoclonal bispecific antibody

Outcome Measures

Primary Outcome Measures

Determine the safety and tolerability profile of XmAb20717 [56 Days]
Treatment-related adverse events as assessed by CTCAE v4.03

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

PART A (Dose Escalation Cohorts)

Melanoma;
Breast carcinoma that is estrogen receptor, progesterone receptor, and Her2 negative (triple-negative breast cancer; TNBC);
Hepatocellular carcinoma;
Urothelial carcinoma;
Squamous cell carcinoma of the head and neck;
Renal cell carcinoma (clear cell predominant type);
Microsatellite instability-high or mismatch repair deficient colorectal carcinoma or endometrial carcinoma;
Non-small cell lung carcinoma;
Gastric or gastroesophageal junction adenocarcinoma
Mesothelioma;
High-grade neuroendocrine carcinoma, including small cell carcinoma of the lung
Cervical cancer;
Squamous cell carcinoma of the anus

PART B (Dose Expansion Cohorts):

Melanoma
Renal cell carcinoma (clear cell predominant type)
Non-small cell lung carcinoma
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)
Nasopharyngeal carcinoma
Cholangiocarcinoma
Basal cell carcinoma
Squamous cell carcinoma of the anus
Mesothelioma
Ovarian or fallopian tube carcinoma
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)
Thymoma
Thymic carcinoma
Squamous cell carcinoma of the penis
Neuroendocrine carcinoma
Vulvar cancer
Non-squamous cell salivary gland carcinoma (except adenoid cystic carcinoma)
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute	Los Angeles	California	United States	90048
2	UCLA Hematology-Oncology Clinic (Westwood)	Los Angeles	California	United States	90095
3	University of California San Diego Moores Cancer Center	San Diego	California	United States	92093-0698
4	University of California San Francisco Medical Center	San Francisco	California	United States	94115
5	Emory University	Atlanta	Georgia	United States	30322
6	University of Chicago Medicine	Chicago	Illinois	United States	60637
7	The University of Kansas Clinical Research Center	Fairway	Kansas	United States	66205
8	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
9	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York	United States	10016
10	Columbia University Medical Center - Herbert Irving Pavilion	New York	New York	United States	10032
11	Providence Portland Medical Center	Portland	Oregon	United States	97213
12	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
13	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania	United States	15232
14	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
15	University of Utah, Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112
16	Emily Couric Clinical Cancer Center	Charlottesville	Virginia	United States	22903
17	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109