Zanzalintinib + Ipilimumab + Nivolumab for Soft Tissue Sarcoma

Overseen By Brian A Van Tine, M.D., Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must not be taking: Anticoagulants, CYP inhibitors

Disqualifiers: Brain metastases, Autoimmune disease, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

18 Participants Needed

Trial Summary

What is the purpose of this trial?

The investigators hypothesize that zanzalintinib in combination with ipilimumab and nivolumab will be well tolerated and serve as a potential therapeutic strategy in metastatic soft tissue sarcoma (mSTS) including myxofibrosarcoma, undifferentiated pleomorphic sarcoma, dedifferentiated liposarcoma, cutaneous angiosarcoma, and undifferentiated sarcoma histologies.

Research Team

Brian A Van Tine, M.D., Ph.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for adults with metastatic soft tissue sarcoma who've had 1-3 prior treatments (except alveolar soft part sarcoma patients). They must have progressing disease, not be pregnant, agree to contraception, and have good performance status. Exclusions include heart issues, certain other cancers or therapies recently received, autoimmune diseases, major surgery within a specific timeframe, and inability to swallow pills.

Inclusion Criteria

I've had 1-3 treatments for my cancer since it spread, but it's still growing.

I agree to use effective birth control during and after the study.

I am not pregnant and can become pregnant.

Exclusion Criteria

My heart's electrical cycle is longer than normal.

My sarcoma is caused by a genetic change, but it's not ASPS.

I cannot swallow pills or liquid medicine.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Zanzalintinib, Nivolumab, and Ipilimumab. Zanzalintinib is self-administered daily, while Nivolumab and Ipilimumab are administered intravenously every 3 weeks for 4 doses. After 4 cycles, Ipilimumab is discontinued, and Nivolumab is continued every 4 weeks with daily Zanzalintinib.

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of treatment-emergent adverse events and objective response rate.

60 months

Treatment Details

Interventions

• Ipilimumab
• Nivolumab
• Zanzalintinib

Trial Overview The study tests the combination of Zanzalintinib with Ipilimumab and Nivolumab in treating metastatic soft tissue sarcomas. It aims to determine if this drug combo is safe and effective as a new treatment strategy for these cancer types.

Participant Groups

Group I: Expansion: Zanzalintinib + Nivolumab + Ipilimumab Experimental Treatment 3 Interventions

Zanzalintinib dose determined in Dose Escalation by mouth once per day is self administered daily, and nivolumab 3 mg/kg intravenously and ipilimumab 1 mg/kg intravenously are administered intravenously every 3 weeks for a total of 4 doses. After completion of the first 4 cycles, ipilimumab is discontinued while nivolumab 480 mg intravenously is continued every 4 weeks in combination with daily zanzalintinib.

Group II: Dose Escalation Dose Level 2: Zanzalintinib + Nivolumab + Ipilimumab Experimental Treatment 3 Interventions

Zanzalintinib 60 mg by mouth once per day is self administered daily, and nivolumab 3 mg/kg intravenously and ipilimumab 1 mg/kg intravenously are administered intravenously every 3 weeks for a total of 4 doses. After completion of the first 4 cycles, ipilimumab is discontinued while nivolumab 480 mg intravenously is continued every 4 weeks in combination with daily zanzalintinib.

Group III: Dose Escalation Dose Level 1 (starting dose): Zanzalintinib + Nivolumab + Ipilimumab Experimental Treatment 3 Interventions

Zanzalintinib 40 mg by mouth once per day is self administered daily, and nivolumab 3 mg/kg intravenously and ipilimumab 1 mg/kg intravenously are administered intravenously every 3 weeks for a total of 4 doses. After completion of the first 4 cycles, ipilimumab is discontinued while nivolumab 480 mg intravenously is continued every 4 weeks in combination with daily zanzalintinib.

Group IV: Dose Escalation Dose Level -1: Zanzalintinib + Nivolumab + Ipilimumab Experimental Treatment 3 Interventions

Zanzalintinib 20 mg by mouth once per day is self administered daily, and nivolumab 3 mg/kg intravenously and ipilimumab 1 mg/kg intravenously are administered intravenously every 3 weeks for a total of 4 doses. After completion of the first 4 cycles, ipilimumab is discontinued while nivolumab 480 mg intravenously is continued every 4 weeks in combination with daily zanzalintinib.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Exelixis

Industry Sponsor

Trials

126

Recruited

20,500+

Michael M. Morrissey

Exelixis

Chief Executive Officer since 2010

PhD in Chemistry from Harvard University, BSc in Chemistry from the University of Wisconsin

Vicki L. Goodman

Exelixis

Chief Medical Officer since 2022

MD