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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for advanced melanoma, a type of skin cancer. Researchers aim to assess the safety and tolerability of two new drugs, XmAb22841 and XmAb23104, when used together. These drugs enhance the body's immune response against cancer. Individuals with advanced melanoma who have not responded to certain treatments might be suitable candidates. The University of California Melanoma Consortium conducts the trial. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Do I have to stop taking my current medications for the trial?

The trial requires participants to stop certain therapies before starting the study drugs, including chemotherapy, radiation, biological cancer therapy, and investigational agents. If you are currently on these treatments, you will need to discontinue them before participating in the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that XmAb22841 and XmAb23104 are undergoing tests together to determine their effectiveness in treating advanced melanoma. This marks the first human trial of these treatments, so information about their safety remains limited. These treatments are special antibodies targeting two specific proteins on T cells. They aim to enhance the immune system's response and may cause fewer side effects than current treatments.

The study is in an early phase, meaning researchers closely observe how patients handle the treatments and monitor any side effects. Participants will be carefully monitored to ensure their safety during the treatment process. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about XmAb22841 and XmAb23104 for melanoma because these treatments represent a new generation of cancer therapies known as bi-specific antibodies. Unlike traditional therapies that target a single protein, these bi-specific antibodies simultaneously target multiple proteins involved in cancer growth: XmAb22841 targets CTLA-4 and LAG3, while XmAb23104 targets PD1 and ICOS. This dual-targeting approach may enhance the immune system's ability to attack cancer cells more effectively than current standard treatments like single-agent checkpoint inhibitors. This novel mechanism of action offers hope for improved outcomes in melanoma patients where existing therapies may fall short.

What evidence suggests that this trial's treatments could be effective for melanoma?

This trial will evaluate the use of bi-specific antibodies for melanoma, specifically XmAb22841 and XmAb23104, in different dose escalation cohorts. Studies have shown that combining various immune therapies can benefit patients with advanced melanoma. XmAb22841, which participants in this trial may receive, targets CTLA-4 and LAG3, proteins that regulate the immune system, potentially enhancing the body's ability to fight cancer. Research suggests that adding LAG3 blockers to PD-1 blockers has yielded good results with manageable side effects. XmAb23104, another treatment option in this trial, targets PD-1 and ICOS, aiming to boost the immune system and overcome resistance to current treatments. Although the data remains early, these combined therapies show promise for better control of melanoma. ^{1 6 7 8 9}

Who Is on the Research Team?

Adil Daud

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

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 previously received BRAF targeted therapies.

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

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

Exclusion Criteria

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

I am on long-term steroid treatment above normal replacement levels.

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS9595

Phase Ib/II study of XmAb23104 (PD1 X ICOS) and ... We postulate that treatment with XmAb23104 and XmAb22841 will enhance immune activation, overcome resistance, and improve disease control for patients ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9599469/

LAG3-PD1 or CTLA4-PD1 Inhibition in Advanced Melanoma We performed an indirect cross-comparison of LAG3-PD1 and CTLA4-PD1 inhibition in patients with previously untreated advanced melanoma.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05695898

XmAb23104 (PD1 X ICOS) and XmAb22841 (CTLA-4 ... 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 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10357068/

The introduction of LAG-3 checkpoint blockade in melanoma LAG-3 inhibition in combination with PD-1 inhibition offered impressive efficacy with modest increases in toxicity over single agent PD-1 inhibitor.

5. nature.com nature.com/articles/s41571-022-00602-8

LAG3 inhibition improves outcomes Immune-checkpoint inhibitors targeting PD-1 and CTLA4 have dramatically improved the outcomes of patients with metastatic melanoma; however, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12047404/

Advances in LAG3 cancer immunotherapeutics - PMC NCT05695898 is the first trial to target four receptors: LAG3, CTLA4, PD1, and ICOS using two BsAbs, XmAb22841 (CTLA4 x LAG3) and Xmab23104 (PD1 x ICOS), in ...

7. adisinsight.springer.com adisinsight.springer.com/trials/700360994

Phase Ib/II Study of XmAb23104 (PD1 X ICOS ... - AdisInsight 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 ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05695898

XmAb23104 (PD1 X ICOS) and XmAb22841 (CTLA-4 ... 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 ...

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2019.37.15_suppl.e14141

Effect of antibiotic exposure in patients with metastatic ... 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 ...