Neoplasms

All Conditions

Rare Diseases

Sarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

Patients will receive the recommended phase II dose of XmAb23104 monotherapy on day 1 and 15 of each 28-day cycle. Patients will continue XmAb23104 (day 1 \& 15, q 28 days) for up to 24 months depending on their response and tolerability to treatment. Treatment will be continued until progressive disease (PD) or toxicity or a total of 24 months of study therapy has been completed.

XmAb23104 (10 mg/kg) intravenously on days 1 and 15 of each 28-day cycle. XmAb23104 will be administered by IV infusion at a constant rate over 1 hour.

XmAb23104

Ciara Kelly, MBBCh BAO

The purpose of this study is to find out whether the study drug, XmAb23104, is an effective treatment for advanced sarcoma. The researchers will also look at whether XmAb23104 is safe and causes few or mild side effects in participants.

This phase II, open-label, single-center study.

A Study of XmAb23104 in People With Sarcoma

Phase II Study of XmAb23104 (Targeting PD-1 and ICOS), in Patients With Advanced Sarcoma

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Xencor, Inc.

Memorial Sloan Kettering Cancer Center

Skin and Connective Tissue Diseases

Nervous System Diseases

Melanoma

Central Nervous System Diseases

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Immune Checkpoint Inhibitors

Participants will receive 0.3 mg/kg of XmAb22841 (CTLA-4 X LAG3) in combination with 10 mg/kg of XmAb23104 (PD1 X ICOS) on days 1 \& 15 of a 28 day cycles for up to 4 cycles. After Cycle 4, participants will receive 10 mg/kg of XmAb23104 (PD1 X ICOS) monotherapy up to an additional 20 cycles. Participants may receive treatments up to 24 total cycles, or until unacceptable toxicity or progressive disease; whichever comes first.

After the safety and tolerability for cohort 1 has been evaluated, participants will receive 1 mg/kg of XmAb22841 (CTLA-4 X LAG3) in combination with 10 mg/kg of XmAb23104 (PD1 X ICOS) on days 1 \& 15 of a 28 day cycles for up to 4 cycles. After Cycle 4, participants will receive 10 mg/kg of XmAb23104 (PD1 X ICOS) monotherapy up to an additional 20 cycles. Participants may receive treatments up to 24 total cycles, or until unacceptable toxicity or progressive disease; whichever comes first.

After the safety and tolerability for cohort 2 has been evaluated, participants will receive 3 mg/kg of XmAb22841 (CTLA-4 X LAG3) in combination with 10 mg/kg of XmAb23104 (PD1 X ICOS) on days 1 \& 15 of a 28 day cycles for up to 4 cycles. After Cycle 4, participants will receive 10 mg/kg of XmAb23104 (PD1 X ICOS) monotherapy up to an additional 20 cycles. Participants may receive treatments up to 24 total cycles, or until unacceptable toxicity or progressive disease; whichever comes first.

XmAb22841

Adil Daud, MD

This is a first-in-human, multi-center, multi-cohort, open-label, phase Ib/II study of XmAb22841 (CTLA-4 X LAG3) administered in combination with XmAb23104 (PD1 X ICOS) in participants with a histologically or cytologically confirmed diagnosis of an advanced/metastatic melanoma. XmAb22841 (CTLA-4 X LAG3) is a bi-specific antibody targeting two different T cell membrane proteins responsible for regulation of T cell activity. It offers potential immunologic and safety advantages over existing therapies. XmAb22841 (CTLA-4 X LAG3) is being evaluated in this clinical study designed to assess the safety, tolerability, PK, and PD of escalating doses of XmAb22841 (CTLA-4 X LAG3) administered in combination with XmAb23104 (PD1 X ICOS)

The study will be conducted through the University of California Melanoma Consortium (UCMC).

PRIMARY OBJECTIVES:

I. Dose Escalation Phase (Part 1): To estimate the recommended phase 2 dose (RP2D) of XmAb22841 (CTLA-4 X LAG3) in combination XmAb23104 (PD1 X ICOS).

II. Dose Expansion Phase (Part 2): To assess clinical response as measured by objective response rate of patients treated with XmAb22841 (CTLA-4 X LAG3) in combination XmAb23104 (PD1 X ICOS)

SECONDARY OBJECTIVES:

I. To evaluate the pharmacokinetics (PK) and anti-drug antibody (ADA) immunogenicity of XmAb23104 (PD1 X ICOS) and XmAb22841 (CTLA-4 X LAG3) (Dose Escalation (Part 1) \& Dose Expansion (Part 2)).

II. To evaluate the clinical efficacy of XmAb23104 (PD1 X ICOS) and XmAb22841 (CTLA-4 X LAG3) (Dose Expansion (Part 2)).

EXPLORATORY OBJECTIVES:

I. To identify molecular (genomic, metabolic, and/or proteomic) biomarkers that may be indicative of clinical response/resistance, safety, pharmacodynamic activity, and/or the mechanism of action of XmAb22841 (CTLA-4 X LAG3) administered in combination with XmAb23104 (PD1 X ICOS) (Dose Escalation (Part 1) \& Dose Expansion(Part 2)).

OUTLINE:

Participants will initially be enrolled in the Dose Escalation Phase (Part 1).

\*\*PHASE 2 Dose Expansion (Part 2) will not be initiated\*\*.

Participants may continue trial therapy until the earlier of radiographic disease progression, withdrawal, unacceptable toxicity, completion of 24 cycles of XmAb23104 (PD1 X ICOS), or other treatment discontinuation due to unacceptable toxicity, participant withdrawal, progressive disease or death. The entire treatment duration of twenty-four 28-day cycles is approximately 2 years. After discontinuing trial therapy, participants will be followed for toxicity, response, and overall survival every 12 weeks for up to 5 years from initiation of study treatment.

The Phase 2 portion of the study will not be initiated.

XmAb23104 (PD1 X ICOS) and XmAb22841 (CTLA-4 X LAG3) in Treating Melanoma Prior Immune Checkpoint Inhibitor Therapy

Phase Ib/II Study of XmAb23104 (PD1 X ICOS) and XmAb22841 (CTLA-4 X LAG3) Combination in Metastatic Melanoma Refractory to Prior Immune Checkpoint Inhibitor Therapy With and Without CNS Disease

The number of all treatment-emergent adverse events (AEs) for each dose level and cohort, as determined by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be reported for each cohort in the dose escalation phase.

The number of all treatment-emergent, immune-related adverse events (irAEs) for each dose level and cohort, as determined by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be reported for each cohort in the dose escalation phase.

The DLT evaluation period for the initial cohort of n=3 patients will be 6 weeks after beginning treatment to account for possible delayed DLTs. The number participants experiencing DLTs during the evaluation period will be reported for each cohort in in the dose escalation phase.

Objective response (defined as a Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 best response of partial response (PR) or CR) will be assessed for each individual participant for a period of 5 years from the time of initiation of study treatment, or until CR/PR is recorded, or progression is observed, whichever occurs first for participants in the dose expansion phase

Serum levels of XmAb23104 and XmAb22841 will be assessed longitudinally to determine the AUC beginning on the first day of treatment and individual participant through the safety follow up visit.

Serum levels of XmAb23104 and XmAb22841 to determine the minimum concentration will be assessed longitudinally beginning on the first day of treatment and individual participant through the safety follow up visit.

Serum levels of XmAb23104 and XmAb22841 to determine the maximum concentration will be assessed longitudinally beginning on the first day of treatment and individual participant through the safety follow up visit.

Serum Anti-drug antibodies (ADAs) will be assessed longitudinally beginning on the first day of treatment and individual participant through the safety follow up visit.

PFS will be assessed for a period of 5 years from the time of initiation of study treatment, or until progression or death due to any cause, whichever occurs first for participants in Cohorts A \& B (dose expansion phase).

OS will be assessed for a period of 5 years from the time of initiation of study treatment, or until death due to any cause, whichever occurs first for participants in Cohorts A \& B (dose expansion phase).

DoR will be assessed from the first date of response (CR or PR per RECIST 1.1) for a period of 5 years from the time of initiation of study treatment, or until the date of progression or death due to any cause, whichever occurs first for participants Cohorts A \& B (dose expansion phase).

Clinical benefit (defined as a RECIST 1.1 response of stable disease (SD) for \> 6 months, PR, or CR) will be assessed for a period of 5 years from the time of initiation of study treatment, or until SD \> 6 months/CR/PR is recorded, or progression is observed, whichever occurs first for participants in Cohorts A \& B (dose expansion phase).

CNS response (defined as a RECIST 1.1 CNS best response of PR or CR) will be assessed for a period of 5 years from the time of initiation of study treatment, or until CNS CR/PR is recorded, or CNS progression is observed, whichever occurs first for participants in Cohort B only.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study of XmAb23104 in People With Sarcoma	NCT05879185	Sarcoma	XmAb23104	18 Years -	Memorial Sloan Kettering Cancer Center
XmAb23104 (PD1 X ICOS) and XmAb22841 (CTLA-4 X LAG3) in Treating Melanoma Prior Immune Checkpoint Inhibitor Therapy	NCT05695898	Metastatic Mela... Advanced Melano...	XmAb22841 XmAb23104	18 Years -	University of California, San Francisco

Spots Global Cancer Trial Database for xmab23104

Every month we try and update this database with for xmab23104 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for xmab23104

Every month we try and update this database with for xmab23104 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for xmab23104 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.