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Zanzalintinib in Combination With Ipilimumab and Nivolumab in Patients With Metastatic Soft Tissue Sarcoma

ConditionMetastatic Soft-tissue Sarcoma
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorWashington University School of Medicine

About 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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Histologically or cytologically confirmed soft tissue sarcoma that is metastatic or unresectable.

Must have received at least one but no more than 3 lines of therapy in the metastatic setting, with progression on last line of therapy. Neoadjuvant or adjuvant therapy completed more than one year prior does not count towards as a line of therapy in the metastatic. Individuals with alveolar soft part sarcoma may enroll without being refractory to at least one line of therapy.

Measurable disease per RECIST 1.1.

At least 18 years of age.

Disqualifiers

Translocation-driven sarcoma except for ASPS.

Prior treatment with zanzalintinib, cabozantinib, PD-1 inhibitor (eg, cemiplimab, nivolumab, pembrolizumab), PD-L1 inhibitor (eg, atezolizumab, avelumab, durvalumab), or CTLA-4 inhibitor (eg, ipilimumab).

Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.

Receipt of any type of cytotoxic, biologic, or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment.

Trial design

Design model

Sequential

Treatments tested in this trial

  • Zanzalintinib

    Drug

    Zanzalintinib will be supplied by Exelixis, Inc.

  • Ipilimumab

    Drug

    Ipilimumab will be commercially sourced.

  • Nivolumab

    Drug

    Nivolumab will be commercially sourced.

Treatment groups

18 Participants
are divided into 4 treatment groups
Group A: Dose Escalation Dose Level 1 (starting dose): Zanzalintinib + Nivolumab + IpilimumabExperimental treatment 3 interventions
Group B: Dose Escalation Dose Level 2: Zanzalintinib + Nivolumab + IpilimumabExperimental treatment 3 interventions
Group C: Dose Escalation Dose Level -1: Zanzalintinib + Nivolumab + IpilimumabExperimental treatment 3 interventions
Group D: Expansion: Zanzalintinib + Nivolumab + IpilimumabExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

Occurrence of dose-limiting toxicities (DLTs)

DLTs are defined in the protocol.

Time frame
Through day 42

Secondary outcomes

1

Frequency and grades of treatment-emergent adverse events (TEAEs)

Graded per CTCAE v5.0.

Time frame
From start of treatment through 100 days after completion of treatment (estimated to be 24 months and 100 days)
2

Rate of treatment discontinuation due to treatment-emergent adverse events (TEAEs)

Time frame
From start of treatment through completion of treatment (estimated to be 24 months)
3

Objective response rate (ORR) per RECIST 1.1 criteria

* Objective response (OR) is defined as number of participants with complete response (CR) or partial response (PR). * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. * Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Time frame
Through completion of treatment (estimated to be 24 months)
4

Clinical benefit rate (CBR) per RECIST 1.1 criteria

* Clinical benefit is defined complete response (CR), partial response (PR) or stable disease (SD) for 6 weeks. * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. * Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. * Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Time frame
Through completion of treatment (estimated to be 24 months)

Other outcomes

Sponsors and contacts

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Washington University School of Medicine

Lead sponsor

Exelixis

Collaborator

Source ClinicalTrials.gov
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