Study of Zanzalintinib in Combination With Immuno-Oncology Agents in Participants With Solid Tumors
NCT ID: NCT05176483
Last Updated: 2026-01-20
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
ACTIVE_NOT_RECRUITING
PHASE1
1314 participants
INTERVENTIONAL
2021-12-14
2030-06-28
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
In the Expansion Stage, the safety and efficacy of zanzalintinib as monotherapy and in combination therapy will be further evaluated in tumor-specific Expansion Cohorts.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
An Investigational Immuno-therapy Study to Assess the Safety, Tolerability and Effectiveness of Anti-LAG-3 With and Without Anti-PD-1 in the Treatment of Solid Tumors
NCT01968109
Study of XB002 in Subjects With Solid Tumors (JEWEL-101)
NCT04925284
Study of Safety and Tolerability of Nivolumab Treatment Alone or in Combination With Relatlimab or Ipilimumab in Head and Neck Cancer
NCT04080804
A Study Comparing Nivolumab, Nivolumab in Combination With Ipilimumab and Placebo in Participants With Localized Kidney Cancer Who Underwent Surgery to Remove Part of a Kidney
NCT03138512
A Study of Oral 7HP349 (Alintegimod) in Combination With Ipilimumab Followed by Nivolumab Monotherapy
NCT06362369
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Zanzalintinib + Nivolumab Dose-Escalation Cohorts
Approximately 12 participants will accrue across 1-2 dose levels of Zanzalintinib following the "rolling 6" design.
Zanzalintinib
Zanzalintinib orally once daily (qd)
Nivolumab
360 mg IV infusion once every 3 weeks (q3w)
Zanzalintinib + Nivolumab + Ipilimumab Dose-Escalation Cohorts
Approximately 12 participants will accrue across 1-2 dose levels of Zanzalintinib following the "rolling 6" design.
Zanzalintinib
Zanzalintinib orally once daily (qd)
Ipilimumab
1 mg/kg IV infusion once every 3 weeks (q3w) for maximum of four doses
Nivolumab
3 mg/kg IV infusion once every 3 weeks (q3w) for first four doses, and then 480 mg IV infusion once every 4 weeks (q4w)
Zanzalintinib + Nivolumab Expansion Cohorts
The recommended dose from the dose-escalation stage may be further explored in tumor-specific cohorts.
Zanzalintinib
Zanzalintinib orally once daily (qd)
Nivolumab
480 mg IV infusion once every 4 weeks (q4w)
Zanzalintinib + Nivolumab + Ipilimumab Expansion Cohorts
The recommended dose from the dose-escalation stage may be further explored in tumor-specific cohorts.
Zanzalintinib
Zanzalintinib orally once daily (qd)
Ipilimumab
1 mg/kg IV infusion once every 3 weeks (q3w) for maximum of four doses
Nivolumab
3 mg/kg IV infusion once every 3 weeks (q3w) for first four doses, and then 480 mg IV infusion once every 4 weeks (q4w)
Zanzalintinib Single-Agent Expansion Cohorts
Zanzalintinib
Zanzalintinib orally once daily (qd)
Zanzalintinib + Nivolumab + Relatlimab Dose-Escalation Cohorts
Approximately 12 participants will accrue across 1-2 dose levels of Zanzalintinib following the "rolling 6" design.
Zanzalintinib
Zanzalintinib orally once daily (qd)
Nivolumab + Relatlimab
IV administration of nivolumab + relatlimab
Zanzalintinib + Nivolumab + Relatlimab Expansion Cohorts
The recommended dose from the dose-escalation stage may be further explored in tumor-specific cohorts.
Zanzalintinib
Zanzalintinib orally once daily (qd)
Nivolumab + Relatlimab
IV administration of nivolumab + relatlimab
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Zanzalintinib
Zanzalintinib orally once daily (qd)
Nivolumab
360 mg IV infusion once every 3 weeks (q3w)
Ipilimumab
1 mg/kg IV infusion once every 3 weeks (q3w) for maximum of four doses
Nivolumab
3 mg/kg IV infusion once every 3 weeks (q3w) for first four doses, and then 480 mg IV infusion once every 4 weeks (q4w)
Nivolumab
480 mg IV infusion once every 4 weeks (q4w)
Nivolumab + Relatlimab
IV administration of nivolumab + relatlimab
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Dose-Escalation Cohorts: Participants with a solid tumor that is unresectable or metastatic and for which life-prolonging therapies do not exist or available therapies are intolerable or no longer effective.
* Expansion Cohort 1 (ccRCC): Participants with unresectable advanced or metastatic RCC with a clear cell component who have not received prior systemic therapy.
* Note: Prior non-vascular endothelial growth factor (VEGF) targeted adjuvant or neoadjuvant is allowed if disease recurrence occurred 6 months after the last dose.
* Expansion Cohort 2 (ccRCC): Participants with unresectable advanced or metastatic RCC with a clear cell component.
* Must have radiographically progressed after a combination therapy consisting of a Programmed Cell Death Protein 1 (PD-1)/Programmed death-ligand 1 (PD-L1) targeting monoclonal antibody (mAb) with a Vascular endothelial growth factor (receptor) tyrosine kinase inhibitor (VEGFR-TKI) or a PD-1 targeting mAb with a CTLA-4 mAb as the preceding line of therapy.
* Must have received no more than one prior systemic anticancer therapy for unresectable advanced or metastatic renal cell carcinoma.
* Expansion Cohort 3 (mCRPC): Men with metastatic adenocarcinoma of the prostate.
* Must have progressed during or after one novel hormone therapy (NHT) given for castration-sensitive locally advanced (T3 or T4) or metastatic castration-sensitive prostate cancer (CSPC), M0 CRPC, or mCRPC.
* Expansion Cohort 4 (UC, ICI-naive): Participants with histologically confirmed unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including the renal pelvis, ureter, urinary bladder, or urethra).
* Must have progressed during or after prior first-line platinum-based combination therapy, including participants who received prior neoadjuvant or adjuvant platinum-containing therapy with disease recurrence \< 12 months from the end of last therapy.
* Must have received no more than 1 prior line of systemic anticancer therapy for unresectable, locally advanced or metastatic disease.
* Expansion Cohort 5 (post enfortumab vedotin \[EV\] and ICI): Participants with histologically confirmed unresectable, locally advanced or metastatic predominant urothelial carcinoma.
* Progressive disease following prior EV or ineligible for EV, and progression following prior PD-1/PD-L1 inhibitor or ineligible for PD-1/PD-L1 inhibitor.
* Prior receipt of platinum-based therapy allowed but not required.
* Prior therapy with other agents allowed but not required.
* Expansion Cohort 6 (nccRCC): Participants with unresectable advanced or metastatic nccRCC of the following subtypes: Papillary, unclassified RCC, and translocation-associated, Fumarate Hydratase (FH) deficient and Succinate Dehydrogenase (SDH) deficient. Among the eligible histologic subtypes, sarcomatoid features are allowed.
* No prior systemic anticancer therapy is allowed except adjuvant or neoadjuvant therapy if disease recurrence occurred at least 6 months after the last dose.
* Expansion Cohort 7 (HCC): Participants with locally advanced, or metastatic and/or unresectable HCC that is not amenable to curative treatment or locoregional therapy.
* Expansion Cohort 8 (NSCLC): Participants with Stage IV non-squamous NSCLC with positive PD-L1 expression (tumor proportion score \[TPS\] 1-49%) and without prior systemic anticancer therapy for metastatic disease.
* Expansion Cohort 9 (NSCLC): Participants with Stage IV non-squamous NSCLC who have radiologically progressed following treatment with one prior immune checkpoint inhibitor (anti-PD-1 or anti-PD-L1) for metastatic disease.
* Expansion Cohort 10 (CRC): Participants with histologically confirmed unresectable, locally advanced, or metastatic adenocarcinoma of the colon or rectum.
* Expansion Cohort 11 (HNSCC): Participant with inoperable, refractory, recurrent or metastatic HNSCC of the oral cavity, oropharynx, hypopharynx, and larynx. PD-L1 combined positive score (CPS) ≥1.
* Expansion Cohort 12 (ccRCC): Participants with unresectable advance or metastatic RCC with a clear cell component, including participants who also have a sacromatoid feature.
* Must have received no more than two prior lines of systemic anticancer therapy for unresectable advanced or metastatic renal cell carcinoma
* Expansion Cohort 13 and Cohort 14 (ccRCC 1L): Participants with unresectable advanced or metastatic RCC with a clear component, including participants who also have a sacromatoid feature.
* For all Expansion Cohorts except Cohort 3: Measurable disease per RECIST 1.1 as determined by the Investigator.
* For Expansion Cohorts 1 - 11 Only: Archival tumor tissue material, if available, or fresh tumor tissue if it can be safely obtained.
* Recovery to baseline or ≤ Grade 1 common terminology criteria for adverse events (CTCAE) v5 from AE(s) related to any prior treatments unless AE(s) are deemed clinically nonsignificant by the Investigator and/or stable on supportive therapy.
* Karnofsky Performance Status (KPS) ≥ 70%.
* Adequate organ and marrow function.
* Sexually active fertile participants and their partners must agree to use highly effective methods of contraception.
* Females of childbearing potential must not be pregnant at screening.
Exclusion Criteria
* For all Dose-Escalation Cohorts and Expansion Cohort 2 (ccRCC), 3 (mCRPC), Cohort 5 (UC), Cohort 9 (NSCLC), Cohort 10 (CRC), and Cohort 12: Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
* For Cohort 3 (mCRPC): Receipt of abiraterone within 1 week; cyproterone within 10 days; or receipt of flutamide, nilutamide, bicalutamide, enzalutamide, or other androgen receptor inhibitors within 2 weeks before first dose of study treatment.
* For all Dose-Escalation Cohorts and Expansion Cohort 2 (ccRCC), Cohort 3 (mCRPC), Cohort 5 (UC), Cohort 9 (NSCLC) and Cohort 10 (CRC), and Cohort 12: Receipt of any type of anticancer antibody or systemic chemotherapy within 4 weeks before first dose of study treatment.
* Any complementary medications (eg, herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks before first dose of study treatment.
* Prior external radiation therapy for bone metastasis within 2 weeks, for other tumor sites within 4 weeks, and prior radium-223 therapy within 6 weeks before first dose of study treatment, unless otherwise specified.
* Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment.
* Concomitant anticoagulation with oral anticoagulants, except for specified direct factor Xa inhibitors.
* Administration of a live, attenuated vaccine within 30 days prior to first dose.
* Uncontrolled, significant intercurrent or recent illness.
* Corrected QT interval calculated by the Fridericia formula (QTcF) \> 460 ms for females and \> 450 ms for males per electrocardiogram (ECG) within 14 days before first dose of study treatment.
* Participants with inadequately treated adrenal insufficiency.
* Pregnant or lactating females.
* Any other active malignancy within two years before first dose of study treatment, except for superficial skin cancers, or localized, low-grade tumors deemed cured and not treated with systemic therapy. Incidentally diagnosed prostate cancer is allowed if assessed as stage ≤ T2N0M0 and Gleason score ≤ 6.
* For Cohort 2 (ccRCC, 2L): Receipt of a prior triplet therapy including a VEGFR-TKI, a PD1 targeting mAb, and a CTLA-4 mAb.
* For Cohort 3 (mCRPC): Receipt of a taxane-based chemotherapy for mCRPC.
* For Cohort 4 (UC, ICI-naïve): Participants who have had recurrence within the 6 months of completing adjuvant anti-PD-(L)1 treatment.
* For Cohort 6 (nccRCC, 1L): Participants with chromophobe, renal medullary carcinoma, or pure collecting duct nccRCC.
* For Cohort 7 (HCC):
* Documented hepatic encephalopathy (HE) within 6 months before the first dose.
* Clinically meaningful ascites (ie, ascites requiring paracentesis or escalation in diuretics) within 6 months before randomization.
* Participants who have received any local anticancer therapy including surgery, percutaneous ethanol injection (PEI), radiofrequency ablation (RFA), microwave ablation (MWA), transarterial chemoembolization (TACE), or transarterial radioembolization (TARE) within 28 days prior to first dose.
* Participants with known fibrolamellar carcinoma, sarcomatoid HCC, or mixed hepatocellular cholangiocarcinoma
* For Cohort 10 (CRC, 2L+): Receipt of prior therapy with regorafenib and/or trifluridine + tipiracil (TAS-102).
* For Cohort 11 (HNSCC): Primary tumor site of the nasopharyngeal area.
* For Cohorts 1 (ccRCC, 1L), 2 (ccRCC, 2L), 4, 5 (UC), 7 (HCC), 8 (NSCLC 1L PD-L1 low), 9 (NSCLC, 2L+), 10 (CRC, microsatellite stable \[MSS\], 2L+), and 11 (HNSCC):
* Troponin T (TnT) or I (TnI) \> 2 × institutional upper limit of normal (ULN).
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Exelixis
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Medical Director
Role: STUDY_DIRECTOR
Exelixis
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Exelixis Clinical Site #67
Phoenix, Arizona, United States
Exelixis Clinical Site #1
Tucson, Arizona, United States
Exelixis Clinical Site #123
Palo Alto, California, United States
Exelixis Clinical Site #59
Santa Barbara, California, United States
Exelixis Clinical Site #87
Littleton, Colorado, United States
Exelixis Clinical Site #62
New Haven, Connecticut, United States
Exelixis Clinical Site #49
Newark, Delaware, United States
Exelixis Clinical Site #48
Celebration, Florida, United States
Exelixis Clinical Site #11
Gainesville, Florida, United States
Exelixis Clinical Site #78
Jacksonville, Florida, United States
Exelixis Clinical Site #47
Miami, Florida, United States
Exelixis Clinical Site #61
Plantation, Florida, United States
Exelixis Clinical Site #8
Tampa, Florida, United States
Exelixis Clinical Site #26
Chicago, Illinois, United States
Exelixis Clinical Site #4
Indianapolis, Indiana, United States
Exelixis Clinical Site #122
Louisville, Kentucky, United States
Exelixis Clinical Site #14
Baltimore, Maryland, United States
Exelixis Clinical Site #7
Boston, Massachusetts, United States
Exelixis Clinical Site #65
Detroit, Michigan, United States
Exelixis Clinical Site #13
Detroit, Michigan, United States
Exelixis Clinical Site #68
Rochester, Minnesota, United States
Exelixis Clinical Site #2
Omaha, Nebraska, United States
Exelixis Clinical Site #5
Omaha, Nebraska, United States
Exelixis Clinical Site #55
Las Vegas, Nevada, United States
Exelixis Clinical Site #88
East Brunswick, New Jersey, United States
Exelixis Clinical Site #105
Hackensack, New Jersey, United States
Exelixis Clinical Site #60
New York, New York, United States
Exelixis Clinical Site #6
New York, New York, United States
Exelixis Clinical Site #76
Syracuse, New York, United States
Exelixis Clinical Site #12
Durham, North Carolina, United States
Exelixis Clinical Site #10
Cleveland, Ohio, United States
Exelixis Clinical Site #51
Portland, Oregon, United States
Exelixis Clinical Site #104
Hershey, Pennsylvania, United States
Exelixis Clinical Site #98
Philadelphia, Pennsylvania, United States
Exelixis Clinical Site #32
Pittsburgh, Pennsylvania, United States
Exelixis Clinical Site #24
Pittsburgh, Pennsylvania, United States
Exelixis Clinical Site #9
Myrtle Beach, South Carolina, United States
Exelixis Clinical Site #3
Nashville, Tennessee, United States
Exelixis Clinical Site #46
Austin, Texas, United States
Exelixis Clinical Site #111
Dallas, Texas, United States
Exelixis Clinical Site #89
Dallas, Texas, United States
Exelixis Clinical Site #73
Irving, Texas, United States
Exelixis Clinical Site #50
Plano, Texas, United States
Exelixis Clinical Site #70
Tyler, Texas, United States
Exelixis Clinical Site #66
Charlottesville, Virginia, United States
Exelixis Clinical Site #33
Milwaukee, Wisconsin, United States
Exelixis Clinical Site #116
Albury, , Australia
Exelixis Clinical Site #35
Birtinya, , Australia
Exelixis Clinical Site #16
Brisbane, , Australia
Exelixis Clinical Site #42
Saint Leonards, , Australia
Exelixis Clinical Site #36
Sydney, , Australia
Exelixis Clinical Site #94
Graz, , Austria
Exelixis Clinical Site #31
Salzburg, , Austria
Exelixis Clinical Site #29
Vienna, , Austria
Exelixis Clinical Site #106
Wein, , Austria
Exelixis Clinical Site #39
Anderlecht, , Belgium
Exelixis Clinical Site #37
Kortrijk, , Belgium
Exelixis Clinical Site #85
Besançon, , France
Exelixis Clinical Site #96
Bordeaux, , France
Exelixis Clinical Site #79
Caen, , France
Exelixis Clinical Site #118
Clermont-Ferrand, , France
Exelixis Clinical Site #109
Lyon, , France
Exelixis Clinical Site #92
Marseille, , France
Exelixis Clinical Site #64
Nice, , France
Exelixis Clinical Site #83
Paris, , France
Exelixis Clinical Site #91
Paris, , France
Exelixis Clinical Site #80
Rennes, , France
Exelixis Clinical Site #63
Saint-Herblain, , France
Exelixis Clinical Site #75
Strasbourg, , France
Exelixis Clinical Site #84
Vandœuvre-lès-Nancy, , France
Exelixis Clinical Site #115
Villejuif, , France
Exelixis Clinical Site #103
Essen, , Germany
Exelixis Clinical Site #113
Hamburg, , Germany
Exelixis Clinical Site #108
Heidelberg, , Germany
Exelixis Clinical Site #82
Herne, , Germany
Exelixis Clinical Site #93
Jena, , Germany
Exelixis Clinical Site #112
München, , Germany
Exelixis Clinical Site #102
Nürtingen, , Germany
Exelixis Clinical Site #107
Trier, , Germany
Exelixis Clinical Site #95
Tübingen, , Germany
Exelixis Clinical Site #86
Beersheba, , Israel
Exelixis Clinical Site #72
Haifa, , Israel
Exelixis Clinical Site #52
Jerusalem, , Israel
Exelixis Clinical Site #71
Petah Tikva, , Israel
Exelixis Clinical Site #69
Tel Aviv, , Israel
Exelixis Clinical Site #38
Ẕerifin, , Israel
Exelixis Clinical Site #121
Ancona, , Italy
Exelixis Clinical Site #117
Bologna, , Italy
Exelixis Clinical Site #90
Florence, , Italy
Exelixis Clinical Site #101
Milan, , Italy
Exelixis Clinical Site #81
Milan, , Italy
Exelixis Clinical Site #40
Napoli, , Italy
Exelixis Clinical Site #74
Ravenna, , Italy
Exelixis Clinical Site #30
Grafton, , New Zealand
Exelixis Clinical Site #45
Hamilton, , New Zealand
Exelixis Clinical Site #20
Bydgoszcz, , Poland
Exelixis Clinical Site #28
Gdansk, , Poland
Exelixis Clinical Site #34
Otwock, , Poland
Exelixis Clinical Site #54
Poznan, , Poland
Exelixis Clinical Site #114
Wroclaw, , Poland
Exelixis Clinical Site #41
Badajoz, , Spain
Exelixis Clinical Site #53
Barcelona, , Spain
Exelixis Clinical Site #15
Barcelona, , Spain
Exelixis Clinical Site #27
Barcelona, , Spain
Exelixis Clinical Site #120
L'Hospitalet de Llobregat, , Spain
Exelixis Clinical Site #57
Madrid, , Spain
Exelixis Clinical Site #43
Madrid, , Spain
Exelixis Clinical Site #58
Madrid, , Spain
Exelixis Clinical Site #77
Madrid, , Spain
Exelixis Clinical Site #19
Madrid, , Spain
Exelixis Clinical Site #100
Madrid, , Spain
Exelixis Clinical Site #18
Pamplona, , Spain
Exelixis Clinical Site #119
Santander, , Spain
Exelixis Clinical Site #23
Seville, , Spain
Exelixis Clinical Site #56
Valencia, , Spain
Exelixis Clinical Site #25
Valencia, , Spain
Exelixis Clinical Site #21
Chur, , Switzerland
Exelixis Clinical Site #22
Sankt Gallen, , Switzerland
Exelixis Clinical Site #44
Winterthur, , Switzerland
Exelixis Clinical Site #110
Cambridge, , United Kingdom
Exelixis Clinical Site #99
London, , United Kingdom
Exelixis Clinical Site #97
Middlesex, , United Kingdom
Countries
Review the countries where the study has at least one active or historical site.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2023-510061-10-00
Identifier Type: CTIS
Identifier Source: secondary_id
XL092-002
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.