A Study of XmAb®22841 Monotherapy & in Combination w/ Pembrolizumab in Subjects w/ Selected Advanced Solid Tumors

Hepatocellular Carcinoma Clinical Trial

— DUET-4  

Official title:

A Phase 1 Multiple-Dose Study to Evaluate the Safety and Tolerability of XmAb®22841 Monotherapy and in Combination With Pembrolizumab in Subjects With Selected Advanced Solid Tumors (DUET-4)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03849469
• Other study ID #: XmAb22841-01
• Secondary ID: DUET-4
• Status: Completed
• Phase: Phase 1
• Start date: May 29, 2019
• Est. completion date: February 16, 2023

Study information

• Verified date: March 2023
• 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 and expansion study designed to define a maximum tolerated dose and/or recommended dose of XmAb22841 monotherapy and in combination with pembrolizumab; to assess safety, tolerability, pharmacokinetics, immunogenicity, and anti-tumor activity of XmAb22841 monotherapy and in combination with pembrolizumab in subjects with select advanced solid tumors.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 78
• Est. completion date: February 16, 2023
• Est. primary completion date: February 16, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

PART A (Dose Escalation Cohorts)

1. All subjects' cancer must have progressed after treatment with all available therapies that are known to confer clinical benefit, or are intolerant to treatment, or refuse standard treatment.

2. All subjects must have adequate archival tumor, or give consent to a fresh tumor biopsy.

3. Subjects have an ECOG performance status of 0-1.

4. Subjects in monotherapy and combination therapy cohorts must have histologically or

cytologically confirmed advanced or metastatic solid tumors, including the following:

1. Melanoma

2. Cervical carcinoma

3. Pancreatic carcinoma

4. Breast carcinoma that is estrogen receptor, progesterone receptor, and Her2 negative (TNBC)

5. Hepatocellular carcinoma

6. Urothelial carcinoma

7. Squamous cell carcinoma of the head and neck (HNSCC)

8. Nasopharyngeal carcinoma (NPC)

9. Renal cell carcinoma

10. Colorectal carcinoma or endometrial carcinoma

11. Small cell lung carcinoma or NSCLC

12. Gastric or gastroesophageal junction adenocarcinoma

13. Prostate adenocarcinoma

14. Epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer

15. Intrahepatic cholangiocarcinoma

5. Subjects in the combination cohorts in Part A with XmAb22841 and pembrolizumab may

have an advanced solid tumor that either:

• has progressed after treatment with all available therapies that are known to confer clinical benefit, or is intolerant or has refused standard treatment (as for the XmAb22841 monotherapy cohorts), or
• is of a tumor type for which pembrolizumab is an approved indication and has not previously been treated with an agent targeting PD1 or PDL1. PART B (Dose Expansion Cohorts) XmAb22841 Single Agent Cohort

1. Must have histologically or cytologically confirmed advanced or metastatic solid tumor that has progressed after treatment with all available therapies that are known to confer clinical benefit, or are intolerant to treatment, or refuse standard treatment. Eligible

tumor types include the following:

1. Anti-PD1 refractory melanoma (or any uveal melanoma)

2. Anti-PD1 refractory NSCLC

3. Anti-PD1 refractory renal cell carcinoma (with clear cell component)

4. Anti-PD1 refractory urothelial carcinoma

5. Head and neck squamous cell carcinoma

6. Hepatocellular carcinoma

7. Gastric adenocarcinoma

8. Cervical carcinoma

9. Breast carcinoma that is estrogen receptor, progesterone receptor, and HER2 negative (TNBC)

10. Epithelial ovarian cancer

11. Nasopharyngeal carcinoma

12. Squamous cell anal carcinoma

13. Squamous cell penile carcinoma

14. Squamous cell vulvar carcinoma XmAb22841 + Pembrolizumab Cohorts

1. Anti-PD-1 refractory melanoma (excluding uveal melanoma)

2. Anti-PD-1 naïve melanoma (excluding uveal melanoma)

3. Anti-PD-1 refractory NSCLC

4. Anti-PD1 naïve NSCLC a. Must be PD-L1 high (TPS = 50%), with no EGFR or ALK aberrations

5. Anti-PD1 naïve urothelial carcinoma

1. Must be PDL1 positive (CPS of = 10), or ineligible for any platinum-containing chemotherapy regardless of PDL1 status; or

2. Had disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy

Exclusion Criteria:

1. Prior treatment with an investigational anti-LAG3 therapy.

2. Treatment with any CTLA4 antibody within 16 weeks of the start of study drug for Cohorts 1M, 2M, 3M, 1P, and 2P; within 8 weeks for Cohorts 4M, 5M, 3P, 4P and 4Pi; and within 3 weeks for Cohorts 6M, 7Mi, 7M, 5P, and 6P.

3. Systemic antineoplastic therapy, unconjugated antibody therapy within 4 weeks of the first dose of study treatment; or radiotherapy within 2 weeks of the first dose of study treatment; or small molecule kinase inhibitors within 6 elimination half-lives of the first dose of study treatment.

4. Have received prior therapy with an anti-PD1, anti-PDL1, or anti PDL2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA4, OX 40, CD137) AND were permanently discontinued from that treatment due to an irAE.

5. Failure to recover from any irAE from prior cancer therapy to Grade = 1.

6. Failure to recover from any other toxicity (other than immune-related toxicity) related to previous anticancer treatment to Grade = 2.

7. Active known or suspected autoimmune disease (except that subjects are permitted to enroll if they have vitiligo; type 1 diabetes mellitus; 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).

8. Receipt of an organ allograft.

9. Treatment with antibiotics within 14 days prior to first dose of study drug.

10. Participants with known HIV.

11. Participants with known chronic hepatitis B virus (HBV) infection treated for less than 3 months prior to study enrollment and/or with a detectable HBV viral load; or hepatitis C virus (HCV) infection that has been treated for less than 4 weeks prior to study enrollment and/or with a detectable HCV viral load; or active HBV/HCV coinfection.

Related Conditions & MeSH terms

• Advanced or Metastatic Solid Tumors
• Anus Neoplasms
• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Ovarian Epithelial
• Carcinoma, Squamous Cell
• Cervical Carcinoma
• Cholangiocarcinoma
• Colorectal Carcinoma
• Colorectal Neoplasms
• Endometrial Carcinoma
• Endometrial Neoplasms
• Epithelial Ovarian Cancer
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Gastric or Gastroesophageal Junction Adenocarcinoma
• Hepatocellular Carcinoma
• Intrahepatic Cholangiocarcinoma
• Lung Neoplasms
• Melanoma
• Nasopharyngeal Carcinoma
• Non-small Cell Lung Carcinoma
• Ovarian Neoplasms
• Pancreatic Carcinoma
• Pancreatic Neoplasms
• Primary Peritoneal Carcinoma
• Prostate Carcinoma
• Renal Cell Carcinoma
• Small Cell Lung Carcinoma
• Squamous Cell Anal Cancer
• Squamous Cell Carcinoma of Head and Neck
• Squamous Cell Carcinoma of the Head and Neck
• Squamous Cell Penile Carcinoma
• Squamous Cell Vulvar Carcinoma
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms
• Urothelial Carcinoma
• Vulvar Neoplasms

Intervention

Biological:
• XmAb®22841
Monoclonal bispecific antibody
• Pembrolizumab (Keytruda®)
FDA-approved humanized monoclonal antibody

Locations

Country	Name	City	State
United States	University of Michigan Medical School	Ann Arbor	Michigan
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Winship Cancer Institute, Emory University	Atlanta	Georgia
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Brigham and Women's Health Care Center, Chestnut Hill	Chestnut Hill	Massachusetts
United States	Mary Crowley Cancer Research - Medical City	Dallas	Texas
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	UCSD Medical Center - Encinitas	Encinitas	California
United States	Karmanos Cancer Institute Weisberg Cancer Treatment Center	Farmington Hills	Michigan
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of Iowa Hospital and Clinics	Iowa City	Iowa
United States	Koman Family Outpatient Pavilion	La Jolla	California
United States	UC San Diego Medical Center - La Jolla (Jacobs Medical Center / Thornton Pavilion)	La Jolla	California
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	UCSD Altman Clinical and Translational Research Institute Building (ACTRI)	La Jolla	California
United States	UCSD Perlman Medical Offices	La Jolla	California
United States	UCLA Hematology & Oncology Clinic	Los Angeles	California
United States	Columbia University Medical Center	New York	New York
United States	Laura & Isaac Perlmutter Cancer Center at NYU Langone Health	New York	New York
United States	NYU Langone Medical Center (Tisch Hospital)	New York	New York
United States	Hospital of the University of Pennsylvania - Perelman Center for Advanced Medicine	Philadelphia	Pennsylvania
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	UPMC Shadyside Hospital	Pittsburgh	Pennsylvania
United States	University of Utah, Huntsman Cancer Institute	Salt Lake City	Utah
United States	UC San Diego Medical Center - Hillcrest	San Diego	California
United States	UCSD Rancho Bernardo Medical Office	San Diego	California
United States	UCSD Medical Center - Vista	Vista	California

Sponsors (2)

Lead Sponsor	Collaborator
Xencor, Inc.	ICON Clinical Research

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability profile of XmAb22841 assessed by rates of treatment-related adverse events (AEs), graded by CTCAE v4.03.	Rates of treatment-related adverse events (AEs), graded by CTCAE v4.03, and additionally categorized as either immune-related or non-immune AEs.	56 Days