A Study of XmAb®20717 in Subjects With Selected Advanced Solid Tumors

Hepatocellular Carcinoma Clinical Trial

— DUET-2  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03517488
• Other study ID #: XmAb20717-01
• Secondary ID: DUET-2
• Status: Completed
• Phase: Phase 1
• Start date: July 10, 2018
• Est. completion date: September 6, 2022

Study information

• Verified date: November 2022
• Source: Xencor, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: September 6, 2022
• Est. primary completion date: June 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Anus Neoplasms
• Basal Cell Carcinoma
• Breast Carcinoma
• Breast Neoplasms
• Carcinoma
• Carcinoma, Basal Cell
• Carcinoma, Neuroendocrine
• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Squamous Cell
• Castration-Resistant Prostate Carcinoma
• Cervical Cancer
• Cholangiocarcinoma
• Colorectal Carcinoma
• Colorectal Neoplasms
• Endometrial Carcinoma
• Endometrial Neoplasms
• Fallopian Tube Carcinoma
• Gastric or Gastroesophageal Junction Adenocarcinoma
• Hepatocellular Carcinoma
• Lung Neoplasms
• Malignant Adnexal Neoplasms
• Melanoma
• Mesothelioma
• Mesothelioma, Malignant
• Nasopharyngeal Carcinoma
• Neuroendocrine Carcinoma
• Non-small Cell Lung Carcinoma
• Non-squamous Cell Salivary Gland Carcinoma
• Ovarian Carcinoma
• Renal Cell Carcinoma
• Small Cell Lung Carcinoma
• Solid Tumors With Published Evidence of Anti-tumor Activity With Anti-PD1/PDL1 and/or Anti-CTLA4-directed Therapy
• Squamous Cell Carcinoma of Head and Neck
• Squamous Cell Carcinoma of the Anus
• Squamous Cell Carcinoma of the Head and Neck
• Squamous Cell Carcinoma of the Penis
• Thymic Carcinoma
• Thymoma
• Urothelial Carcinoma
• Uterine Cervical Neoplasms
• Vulvar Carcinoma
• Vulvar Neoplasms

Intervention

Biological:
• XmAb20717
Monoclonal bispecific antibody

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	Emily Couric Clinical Cancer Center	Charlottesville	Virginia
United States	University of Chicago Medicine	Chicago	Illinois
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	The University of Kansas Clinical Research Center	Fairway	Kansas
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute	Los Angeles	California
United States	UCLA Hematology-Oncology Clinic (Westwood)	Los Angeles	California
United States	Columbia University Medical Center - Herbert Irving Pavilion	New York	New York
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Providence Portland Medical Center	Portland	Oregon
United States	University of Utah, Huntsman Cancer Institute	Salt Lake City	Utah
United States	University of California San Diego Moores Cancer Center	San Diego	California
United States	University of California San Francisco Medical Center	San Francisco	California
United States	Seattle Cancer Care Alliance	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Xencor, Inc.	ICON plc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine the safety and tolerability profile of XmAb20717	Treatment-related adverse events as assessed by CTCAE v4.03	56 Days