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

NCT05695898 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: 228511NCI-2023-00868
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Metastatic Melanoma; Advanced Melanoma

Keywords

Immune Checkpoint Inhibitor

Outcome Measures

Primary Outcomes (3)

• Number of Treatment- Emergent Adverse Events (Part 1)

  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.

  Up to 24 months

• Number of Treatment- Emergent, Immune-Related, Adverse Events (Part 1)

  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.

  Up to 24 months

• Number of Participants with Dose Limiting Toxicities (DLT) (Part 1)

  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.

  Up to 42 days

Secondary Outcomes (10)

• Objective Response Rate (Part 2)

  Up to 24 months

• Area under the curve (AUC)

  Up to 24 months

• Minimum concentration (Cmin)

  Up to 25 months

• Mean maximum concentration (Cmax)

  Up to 25 months

• Overall incidence of anti-XmAb23104 and anti-XmAb22841 antibodies

  Up to 25 months

Study Arms (3)

Phase 1b: Dose Escalation (Cohort 1)

EXPERIMENTAL

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.

Drug: XmAb22841; Drug: XmAb23104

Phase 1b: Dose Escalation (Cohort 2)

EXPERIMENTAL

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.

Drug: XmAb22841; Drug: XmAb23104

Phase 1b: Dose Escalation (Cohort 3)

EXPERIMENTAL

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.

Drug: XmAb22841; Drug: XmAb23104

Interventions

XmAb22841 DRUG

Given intravenously (IV)

Also known as: CTLA-4 X LAG3, Bavunalimab

Phase 1b: Dose Escalation (Cohort 1); Phase 1b: Dose Escalation (Cohort 2); Phase 1b: Dose Escalation (Cohort 3)

XmAb23104 DRUG

Given intravenously (IV)

Also known as: PD1 X ICOS, XmAb104

Phase 1b: Dose Escalation (Cohort 1); Phase 1b: Dose Escalation (Cohort 2); Phase 1b: Dose Escalation (Cohort 3)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have a histologically or cytologically confirmed advanced/metastatic melanoma by pathology report. Participants with cutaneous, mucosal, acral and unknown primaries will be allowed.
• Participants must have progressed on either single agent programmed cell death protein 1 (PD1) or combination PD1/ cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibition therapy.
• Participants are allowed to have up to 4 prior lines of therapy in the metastatic setting.
• NOTE: Prior BRAF targeted therapies are allowed. Prior exposure to immunotherapeutics is allowed, including LAG-3, PD1, and PD-L1 inhibitors, provided participant did not experience a \>= Grade 3 (CTCAE v5.0) drug-related toxicity on monotherapy with a Expression of lymphocyte activation gene 3 (LAG-3), PD1, or programmed death-ligand 1 (PD-L1) inhibitor.
• For Dose Escalation Phase, central nervous system (CNS) disease is not required, but it is permitted, provided the following three CNS criteria are met:
• A. CNS lesions must be asymptomatic and stable, as determined by stability on magnetic resonance imaging (MRI) at least 4 weeks prior to study enrollment.
• For Dose Expansion Phase:
• Participants in Expansion Arm A must have metastatic melanoma without CNS disease
• Participants in Expansion Arm B must have metastatic melanoma with CNS disease, and the following three CNS criteria must be met:
• A. CNS lesions must be asymptomatic and stable, as determined by stability on MRI at least 4 weeks prior to study enrollment.

You may not qualify if:

• Participants must have measurable disease according to RECIST 1.1 with the following modification for brain lesions (if brain lesions are present):
• \- Measurable brain lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 5 mm. Measurable lesions for all other non-brain sites are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>=20 mm (\>=2 cm) by chest x-ray or as \>=10 mm (\>=1 cm) with Computerized tomography (CT) scan, MRI, or calipers by clinical exam. NOTE: MRI brain (or equivalent brain imaging) is required at baseline for all patients to characterize brain disease status.
• Age \>=18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Karnofsky \>60%).
• Demonstrate adequate organ function as defined below obtained within 14 days prior to the start of study treatment:
• NOTE: Criteria must be met without packed red blood cell (pRBC) and platelet transfusion within the prior 2 weeks. Participants can be on a stable dose of erythropoietin (\>=approximately 3 months).
• Bone Marrow:
• a) Absolute neutrophil count \>=1,500/microliter (mcL) b) Platelets \>=100,000/mcL c) Hemoglobin \>=9 g/dL or \>5.6 mmol/L
• Renal:
• d) Serum creatinine or creatinine clearance (CrCl) (measured or calculated per institutional standard) OR for participants with creatinine levels \>1.5 × upper limit of normal (ULN): Glomerular Filtration Rate (GFR) must be assessed, Creatinine \<=1.5 × ULN OR for participants with creatinine levels \>1.5 × ULN: GFR \>30 mL/min/1.73 m\^2 calculated per institutional standard method.
• Hepatic:
• e) Total bilirubin (serum) \<=1.5 × ULN, unless elevated due to Gilbert's syndrome and direct bilirubin is within normal limits.
• f) Aspartate aminotransferase (AST)/ (serum glutamic-oxaloacetic transaminase (SGOT) ) \<=2.5 x ULN or For participants with liver metastasis: \<=5 x ULN g) Alanine aminotransferase (ALT)/(serum glutamic-pyruvic transaminase (SGPT)) \<=2.5 x ULN or For participants with liver metastasis: \<= 5 x ULN
• Coagulation:
• h) International Normalized Ratio (INR) or Prothrombin Time (PT) or Activated Partial Thromboplastin Time (aPTT) \<1.5 ULN (unless participant is on therapeutic anticoagulant therapy, in which case the PT/INR or aPTT should be within the range of intended use for the anticoagulant(s)).

Sponsors & Collaborators

• University of California, San Francisco: lead
• Xencor, Inc.: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Adil Daud, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: The Phase 2 Dose Expansion (Part 2) portion of the study was never initiated.

Study Record Dates

• First Submitted: January 13, 2023
• First Posted: January 25, 2023
• Study Start: February 28, 2023
• Primary Completion: April 29, 2024
• Study Completion: April 29, 2024
• Last Updated: March 26, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)