MelanomaPhase 1DUET-4NCT03849469
A Study of XmAb®22841 Monotherapy & in Combination w/ Pembrolizumab in Subjects w/ Selected Advanced Solid Tumors
A Phase 1 study testing XmAb®22841 and Pembrolizumab (Keytruda®) in people with Melanoma and Cervical Carcinoma, run by Xencor, Inc. at 28 sites in United States.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma, Cervical Carcinoma, Pancreatic Carcinoma
- What is being tested?
- XmAb®22841 and Pembrolizumab (Keytruda®)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 28 sitesUnited States
- Study dates
- 29 May 2019to 16 Feb 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- PART A (Dose Escalation Cohorts)
- 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.
- All subjects must have adequate archival tumor, or give consent to a fresh tumor biopsy.
- Subjects have an ECOG performance status of 0-1.
- Subjects in monotherapy and combination therapy cohorts must have histologically or cytologically confirmed advanced or metastatic solid tumors, including the following:
- Melanoma
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- Cervical carcinoma
- Pancreatic carcinoma
- Breast carcinoma that is estrogen receptor, progesterone receptor, and Her2 negative (TNBC)
- Hepatocellular carcinoma
- Urothelial carcinoma
- Squamous cell carcinoma of the head and neck (HNSCC)
- Nasopharyngeal carcinoma (NPC)
- Renal cell carcinoma
- Colorectal carcinoma or endometrial carcinoma
- Small cell lung carcinoma or NSCLC
- Gastric or gastroesophageal junction adenocarcinoma
- Prostate adenocarcinoma
- Epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer
- Intrahepatic cholangiocarcinoma
- 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:
- Anti-PD1 refractory melanoma (or any uveal melanoma)
- Anti-PD1 refractory NSCLC
- Anti-PD1 refractory renal cell carcinoma (with clear cell component)
- Anti-PD1 refractory urothelial carcinoma
- Head and neck squamous cell carcinoma
- Hepatocellular carcinoma
- Gastric adenocarcinoma
- Cervical carcinoma
- Breast carcinoma that is estrogen receptor, progesterone receptor, and HER2 negative (TNBC)
- Epithelial ovarian cancer
- Nasopharyngeal carcinoma
- Squamous cell anal carcinoma
- Squamous cell penile carcinoma
- Squamous cell vulvar carcinoma
- XmAb22841 + Pembrolizumab Cohorts
- Anti-PD-1 refractory melanoma (excluding uveal melanoma)
- Anti-PD-1 naïve melanoma (excluding uveal melanoma)
- Anti-PD-1 refractory NSCLC
- Anti-PD1 naïve NSCLC
- Must be PD-L1 high (TPS ≥ 50%), with no EGFR or ALK aberrations
- Anti-PD1 naïve urothelial carcinoma
- Must be PDL1 positive (CPS of ≥ 10), or ineligible for any platinum-containing chemotherapy regardless of PDL1 status; or
- Had disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy
Who cannot join
- Prior treatment with an investigational anti-LAG3 therapy.
- 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.
- 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.
- 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.
- Failure to recover from any irAE from prior cancer therapy to Grade ≤ 1.
- Failure to recover from any other toxicity (other than immune-related toxicity) related to previous anticancer treatment to Grade ≤ 2.
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- 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).
- Receipt of an organ allograft.
- Treatment with antibiotics within 14 days prior to first dose of study drug.
- Participants with known HIV.
- 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.
Trial locations and contacts
28 sites in 1 country.
28 sites in 1 country
United States28 sites
University of Michigan Medical School
Ann Arbor, Michigan, 48109
Emory University Hospital Midtown
Atlanta, Georgia, 30308
Winship Cancer Institute, Emory University
Atlanta, Georgia, 30322
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Brigham and Women's Health Care Center, Chestnut Hill
Chestnut Hill, Massachusetts, 02467
Mary Crowley Cancer Research - Medical City
Dallas, Texas, 75230
Karmanos Cancer Institute
Detroit, Michigan, 48201
UCSD Medical Center - Encinitas
Encinitas, California, 92024
Karmanos Cancer Institute Weisberg Cancer Treatment Center
Farmington Hills, Michigan, 48334
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
University of Iowa Hospital and Clinics
Iowa City, Iowa, 52242
Koman Family Outpatient Pavilion
La Jolla, California, 92037
UC San Diego Medical Center - La Jolla (Jacobs Medical Center / Thornton Pavilion)
La Jolla, California, 92037
UCSD Altman Clinical and Translational Research Institute Building (ACTRI)
La Jolla, California, 92037
UCSD Perlman Medical Offices
La Jolla, California, 92037
UC San Diego Moores Cancer Center
La Jolla, California, 92093
UCLA Hematology & Oncology Clinic
Los Angeles, California, 90095
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
New York, New York, 10016
NYU Langone Medical Center (Tisch Hospital)
New York, New York, 10016
Columbia University Medical Center
New York, New York, 10032
Hospital of the University of Pennsylvania - Perelman Center for Advanced Medicine
Philadelphia, Pennsylvania, 19104
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
UPMC Shadyside Hospital
Pittsburgh, Pennsylvania, 15232
University of Utah, Huntsman Cancer Institute
Salt Lake City, Utah, 84112
UC San Diego Medical Center - Hillcrest
San Diego, California, 92103
UCSD Rancho Bernardo Medical Office
San Diego, California, 92127
UCSD Medical Center - Vista
Vista, California, 92081
About this study
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)
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.
- Conditions
- Melanoma, Cervical Carcinoma, Pancreatic Carcinoma, Triple Negative Breast Cancer, Hepatocellular Carcinoma, Urothelial Carcinoma
- Being tested
- XmAb®22841, Pembrolizumab (Keytruda®)
- Keywords
- DUET-4, Advanced solid tumors, Metastatic solid tumors, Melanoma, Cervical Cancer, Pancreatic Cancer, Triple Negative Breast Cancer, Hepatocellular/Liver Cancer, Urothelial Cancer, Renal Cell Cancer, Squamous Cell Carcinoma of the Head and Neck, Non-small Cell Lung Cancer, Small Cell Lung Cancer, Gastric Cancer, Gastroesophageal Junction Cancer, Lymphocyte-activation gene 3 (LAG3), Cytotoxic T-lymphocyte-associated protein 4 (CTLA4), Prostate Cancer, Nasopharyngeal carcinoma, Epithelial ovarian cancer
- Medical subject headings
- Melanoma, Uterine Cervical Neoplasms, Pancreatic Neoplasms, Triple Negative Breast Neoplasms, Carcinoma, Hepatocellular, Carcinoma, Transitional Cell, Squamous Cell Carcinoma of Head and Neck, Nasopharyngeal Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XmAb®22841Biological
Monoclonal bispecific antibody
Pembrolizumab (Keytruda®)Biological
FDA-approved humanized monoclonal antibody
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Arm 1: XmAb®22841 Monotherapy Receives: Biological: XmAb®22841 |
| Arm 2 | Experimental | Arm 2: Combination of XmAb®22841 and Pembrolizumab (Keytruda®) Receives: Biological: XmAb®22841; Biological: Pembrolizumab (Keytruda®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 56 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2019
- Study start29 May 2019
- Primary completion16 Feb 2023
- Study completion16 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- Xencor, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- ICON Clinical Research
- Responsible party
- Sponsor
- Investigators
- Benjamin Thompson, MD, PhD, Study director, Xencor, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03849469
- Sponsor's protocol ID
- XmAb22841-01
- Other IDs
- DUET-4
- Acronym
- DUET-4
- Status last verified
- Mar 2023
- First submitted
- 19 Feb 2019
- Last updated
- 30 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wong RL, Yu EY. Refining Immuno-Oncology Approaches in Metastatic Prostate Cancer: Transcending Current Limitations. Curr Treat Options Oncol. 2021 Jan 12;22(2):13. doi: 10.1007/s11864-020-00808-x.
PubMed 33433743
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03849469
- Acronym / sponsor ID
- DUET-4 / XmAb22841-01
- Conditions
- Melanoma, Cervical Carcinoma, Pancreatic Carcinoma, Triple Negative Breast Cancer, Hepatocellular Carcinoma, Urothelial Carcinoma
- Keywords
- DUET-4, Advanced solid tumors, Metastatic solid tumors, Melanoma, Cervical Cancer, Pancreatic Cancer, Triple Negative Breast Cancer, Hepatocellular/Liver Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 78 participants (actual)
- Lead sponsor
- Xencor, Inc.Industry (pharma, biotech, devices)
- Collaborators
- ICON Clinical Research
- Study start
- 29 May 2019 (actual)
- Primary completion
- 16 Feb 2023 (actual)
- Study completion
- 16 Feb 2023 (actual)
- First posted
- 21 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Biological: XmAb®22841Arm 1: XmAb®22841 Monotherapy |
| Arm 2 | Experimental | Biological: XmAb®22841, Biological: Pembrolizumab (Keytruda®)Arm 2: Combination of XmAb®22841 and Pembrolizumab (Keytruda®) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (49 listed)
- PART A (Dose Escalation Cohorts)
- 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.
- All subjects must have adequate archival tumor, or give consent to a fresh tumor biopsy.
- Subjects have an ECOG performance status of 0-1.
- Subjects in monotherapy and combination therapy cohorts must have histologically or cytologically confirmed advanced or metastatic solid tumors, including the following:
Key exclusion criteria (11 listed)
- Prior treatment with an investigational anti-LAG3 therapy.
- 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.
- 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.
- 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.
- Failure to recover from any irAE from prior cancer therapy to Grade ≤ 1.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| XmAb®22841Monoclonal bispecific antibody | Biological | Arm 1, Arm 2 |
| Pembrolizumab (Keytruda®)FDA-approved humanized monoclonal antibody | Biological | Arm 2 |
Primary outcome
Safety and tolerability profile of XmAb22841 assessed by rates of treatment-related adverse events (AEs), graded by CTCAE v4.03.
Time frame: 56 Days
Rates of treatment-related adverse events (AEs), graded by CTCAE v4.03, and additionally categorized as either immune-related or non-immune AEs.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2023.
- Derived from this study: PubMed 33433743Wong RL, Yu EY. Refining Immuno-Oncology Approaches in Metastatic Prostate Cancer: Transcending Current Limitations. Curr Treat Options Oncol. 2021 Jan 12;22(2):13. doi: 10.1007/s11864-020-00808-x.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Benjamin Thompson, MD, PhD study director
Xencor, Inc.
28 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing XmAb®22841 and Pembrolizumab (Keytruda®) in people with Melanoma and Cervical Carcinoma, run by Xencor, Inc. at 28 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 49 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability profile of XmAb22841 assessed by rates of treatment-related adverse events (AEs), graded by CTCAE v4.03. (time frame: 56 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03849469, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2023.