Bi-specific Antibodies for Melanoma

Overseen By Sonia Contreras Martinez

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of California, San Francisco

Must not be taking: Chemotherapy, Immunosuppressants

Disqualifiers: Active infection, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 13

6 Participants Needed

Trial Summary

What is the purpose of this trial?

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).

Research Team

Adil Daud

Principal Investigator

University of California, San Francisco

Eligibility Criteria

Adults (18+) with advanced/metastatic melanoma who have progressed after PD1 or PD1/CTLA-4 therapy can join. They must have acceptable organ function, no severe drug-related toxicity from prior immunotherapies, and meet specific criteria if HIV-positive. Pregnant or breastfeeding individuals, those with active CNS metastases requiring high-dose steroids, uncontrolled conditions, or a history of certain severe reactions to monoclonal antibodies are excluded.

Inclusion Criteria

I have had up to 4 treatments for my cancer after it spread.

I have previously received BRAF targeted therapies.

My organs are functioning well, as tested within the last 14 days.

Exclusion Criteria

I am on certain medications that I cannot or do not want to stop before starting the study drugs.

Has had a severe hypersensitivity reaction to treatment with the study intervention.

I am still experiencing side effects from previous cancer treatments.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of XmAb22841 (CTLA-4 X LAG3) in combination with XmAb23104 (PD1 X ICOS) to determine the recommended phase 2 dose

24 months

Visits on days 1 & 15 of each 28-day cycle

Follow-up

Participants are monitored for safety, response, and overall survival after treatment

5 years

Every 12 weeks

Treatment Details

Interventions

• XmAb22841
• XmAb23104

Trial Overview The trial is testing the combination of two bi-specific antibodies: XmAb22841 (targeting CTLA-4 and LAG3) and XmAb23104 (targeting PD1 and ICOS). It's an early-phase study assessing safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) in participants divided into different cohorts based on their CNS disease status.

Participant Groups

Group I: Phase 1b: Dose Escalation (Cohort 3) Experimental Treatment 2 Interventions

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.

Group II: Phase 1b: Dose Escalation (Cohort 2) Experimental Treatment 2 Interventions

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.

Group III: Phase 1b: Dose Escalation (Cohort 1) Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Xencor, Inc.

Industry Sponsor

Trials

31

Recruited

2,500+