Study of Zanzalintinib in Combination With Immuno-Oncology Agents in Participants With Solid Tumors

NCT05176483 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: XL092-0022023-510061-10-00
• Study Type: interventional
• Target: 1,314
• Locations: 12 countries
• Sites: 117

Brief Summary

This is a multicenter Phase 1b, open label, dose-escalation and cohort-expansion study, evaluating the safety, tolerability, pharmacokinetics (PK), preliminary antitumor activity, and effect of biomarkers of zanzalintinib administered alone, and in combination with nivolumab (doublet), nivolumab + ipilimumab (triplet) and nivolumab + relatlimab (triplet) in participants with advanced solid tumors. 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.

Conditions

Renal Cell Carcinoma (RCC); Metastatic Castration-Resistant Prostate Cancer (mCRPC); Urothelial Carcinoma (UC); Solid Tumor; Hepatocellular Carcinoma (HCC); Non-small Cell Lung Cancer (NSCLC); Colorectal Cancer (CRC); Head and Neck Squamous Cell Carcinoma (HNSCC); Clear Cell Renal Cell Carcinoma (ccRCC); Non-Clear Cell Renal Cell Carcinoma (nccRCC)

Outcome Measures

Primary Outcomes (4)

• Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs), Including Immune-Mediated Adverse Events (imAEs)

  Up to 36 months

• Expansion Stage: Objective Response Rate (ORR)

  To evaluate ORR in participants with measurable disease as assessed by the Investigator per Response Evaluation Criteria in Solid Tumors guideline version 1.1 (RECIST 1.1).

  Up to 24 months

• Expansion Stage Cohort 3 (mCRPC): Progression-Free Survival (PFS)

  To evaluate duration of radiographic PFS as determined per Prostate Working Group 3 (PCWG3) criteria by Blinded Independent Radiology Committee (BIRC).

  Up to 24 months

• Expansion Stage Cohort 10 (CRC): Overall Survival (OS)

  6 months

Secondary Outcomes (2)

• Expansion Stage: Duration of Response (DOR)

  Up to 24 months

• Expansion Stage: Progression-Free Survival (PFS)

  Up to 24 months

Study Arms (7)

Zanzalintinib + Nivolumab Dose-Escalation Cohorts

EXPERIMENTAL

Approximately 12 participants will accrue across 1-2 dose levels of Zanzalintinib following the "rolling 6" design.

Drug: Zanzalintinib; Drug: Nivolumab

Zanzalintinib + Nivolumab + Ipilimumab Dose-Escalation Cohorts

EXPERIMENTAL

Approximately 12 participants will accrue across 1-2 dose levels of Zanzalintinib following the "rolling 6" design.

Drug: Zanzalintinib; Drug: Ipilimumab; Drug: Nivolumab

Zanzalintinib + Nivolumab Expansion Cohorts

EXPERIMENTAL

The recommended dose from the dose-escalation stage may be further explored in tumor-specific cohorts.

Drug: Zanzalintinib; Drug: Nivolumab

Zanzalintinib + Nivolumab + Ipilimumab Expansion Cohorts

EXPERIMENTAL

The recommended dose from the dose-escalation stage may be further explored in tumor-specific cohorts.

Drug: Zanzalintinib; Drug: Ipilimumab; Drug: Nivolumab

Zanzalintinib Single-Agent Expansion Cohorts

EXPERIMENTAL

Drug: Zanzalintinib

Zanzalintinib + Nivolumab + Relatlimab Dose-Escalation Cohorts

EXPERIMENTAL

Approximately 12 participants will accrue across 1-2 dose levels of Zanzalintinib following the "rolling 6" design.

Drug: Zanzalintinib; Drug: Nivolumab + Relatlimab

Zanzalintinib + Nivolumab + Relatlimab Expansion Cohorts

EXPERIMENTAL

The recommended dose from the dose-escalation stage may be further explored in tumor-specific cohorts.

Drug: Zanzalintinib; Drug: Nivolumab + Relatlimab

Interventions

Zanzalintinib DRUG

Zanzalintinib orally once daily (qd)

Also known as: XL092

Zanzalintinib + Nivolumab + Ipilimumab Dose-Escalation Cohorts; Zanzalintinib + Nivolumab + Ipilimumab Expansion Cohorts; Zanzalintinib + Nivolumab + Relatlimab Dose-Escalation Cohorts; Zanzalintinib + Nivolumab + Relatlimab Expansion Cohorts; Zanzalintinib + Nivolumab Dose-Escalation Cohorts; Zanzalintinib + Nivolumab Expansion Cohorts; Zanzalintinib Single-Agent Expansion Cohorts

Nivolumab DRUG

360 mg IV infusion once every 3 weeks (q3w)

Also known as: Opdivo

Zanzalintinib + Nivolumab Dose-Escalation Cohorts

Ipilimumab DRUG

1 mg/kg IV infusion once every 3 weeks (q3w) for maximum of four doses

Also known as: Yervoy

Zanzalintinib + Nivolumab + Ipilimumab Dose-Escalation Cohorts; Zanzalintinib + Nivolumab + Ipilimumab Expansion Cohorts

Nivolumab + Relatlimab DRUG

IV administration of nivolumab + relatlimab

Zanzalintinib + Nivolumab + Relatlimab Dose-Escalation Cohorts; Zanzalintinib + Nivolumab + Relatlimab Expansion Cohorts

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cytologically or histologically confirmed solid tumor that is unresectable, locally advanced or metastatic.
• 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.

You may not qualify if:

• For all Dose-Escalation cohorts: Prior treatment with zanzalintinib. For all Expansion Cohorts: Prior treatment with zanzalintinib, nivolumab, ipilimumab or relatlimab with the following exceptions: Prior PD-1/PD-L1, Lymphocyte-activation gene 3 (LAG-3) and cCytotoxic T lymphocyte associated protein 4 (CTLA-4) targeting therapy for locally advanced or metastatic disease is allowed for Cohort 2 (ccRCC), Cohort 5 (UC), Cohort 9 (NSCLC), and Cohort 12 (ccRCC), and prior treatment in the neoadjuvant or adjuvant setting is allowed for Cohort 13 and Cohort 14 (ccRCC 1L).
• 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.

Sponsors & Collaborators

• Exelixis: lead

Study Sites (122)

Exelixis Clinical Site #67

Phoenix, Arizona, 85054, United States

RECRUITING

Exelixis Clinical Site #1

Tucson, Arizona, 85711, United States

RECRUITING

Exelixis Clinical Site #123

Palo Alto, California, 94304, United States

RECRUITING

Exelixis Clinical Site #59

Santa Barbara, California, 93463, United States

RECRUITING

Exelixis Clinical Site #87

Littleton, Colorado, 80124, United States

RECRUITING

Exelixis Clinical Site #62

New Haven, Connecticut, 06510, United States

RECRUITING

Exelixis Clinical Site #49

Newark, Delaware, 19713, United States

ACTIVE NOT RECRUITING

Exelixis Clinical Site #48

Celebration, Florida, 34747, United States

RECRUITING

Exelixis Clinical Site #11

Gainesville, Florida, 32610, United States

RECRUITING

Exelixis Clinical Site #78

Jacksonville, Florida, 32224, United States

RECRUITING

Exelixis Clinical Site #47

Miami, Florida, 33136, United States

RECRUITING

Exelixis Clinical Site #61

Plantation, Florida, 33322, United States

RECRUITING

Exelixis Clinical Site #8

Tampa, Florida, 33612, United States

RECRUITING

Exelixis Clinical Site #26

Chicago, Illinois, 60612, United States

RECRUITING

Exelixis Clinical Site #4

Indianapolis, Indiana, 46250, United States

RECRUITING

Exelixis Clinical Site #122

Louisville, Kentucky, 40202, United States

RECRUITING

Exelixis Clinical Site #14

Baltimore, Maryland, 21201, United States

RECRUITING

Exelixis Clinical Site #7

Boston, Massachusetts, 02215, United States

RECRUITING

Exelixis Clinical Site #65

Detroit, Michigan, 48201, United States

RECRUITING

Exelixis Clinical Site #13

Detroit, Michigan, 48202, United States

RECRUITING

Exelixis Clinical Site #68

Rochester, Minnesota, 55905, United States

RECRUITING

Exelixis Clinical Site #2

Omaha, Nebraska, 68130, United States

RECRUITING

Exelixis Clinical Site #5

Omaha, Nebraska, 68130, United States

ACTIVE NOT RECRUITING

Exelixis Clinical Site #55

Las Vegas, Nevada, 89052, United States

RECRUITING

Exelixis Clinical Site #88

East Brunswick, New Jersey, 08816, United States

RECRUITING

Exelixis Clinical Site #105

Hackensack, New Jersey, 07601, United States

RECRUITING

Exelixis Clinical Site #60

New York, New York, 10032, United States

RECRUITING

Exelixis Clinical Site #6

New York, New York, 10065, United States

RECRUITING

Exelixis Clinical Site #76

Syracuse, New York, 13210, United States

RECRUITING

Exelixis Clinical Site #12

Durham, North Carolina, 27710, United States

RECRUITING

Exelixis Clinical Site #10

Cleveland, Ohio, 44106, United States

RECRUITING

Exelixis Clinical Site #51

Portland, Oregon, 97239, United States

RECRUITING

Exelixis Clinical Site #104

Hershey, Pennsylvania, 17033, United States

RECRUITING

Exelixis Clinical Site #98

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Exelixis Clinical Site #32

Pittsburgh, Pennsylvania, 15212, United States

RECRUITING

Exelixis Clinical Site #24

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

Exelixis Clinical Site #9

Myrtle Beach, South Carolina, 29572, United States

RECRUITING

Exelixis Clinical Site #3

Nashville, Tennessee, 37203, United States

RECRUITING

Exelixis Clinical Site #46

Austin, Texas, 78705, United States

RECRUITING

Exelixis Clinical Site #111

Dallas, Texas, 75246, United States

RECRUITING

Exelixis Clinical Site #89

Dallas, Texas, 75246, United States

RECRUITING

Exelixis Clinical Site #73

Irving, Texas, 75063, United States

RECRUITING

Exelixis Clinical Site #50

Plano, Texas, 75075, United States

RECRUITING

Exelixis Clinical Site #70

Tyler, Texas, 75601, United States

RECRUITING

Exelixis Clinical Site #66

Charlottesville, Virginia, 22903, United States

RECRUITING

Exelixis Clinical Site #33

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Exelixis Clinical Site #116

Albury, 2640, Australia

RECRUITING

Exelixis Clinical Site #35

Birtinya, 4575, Australia

RECRUITING

Exelixis Clinical Site #16

Brisbane, 4102, Australia

RECRUITING

Exelixis Clinical Site #42

Saint Leonards, 2065, Australia

RECRUITING

Exelixis Clinical Site #36

Sydney, 2109, Australia

RECRUITING

Exelixis Clinical Site #94

Graz, 8036, Austria

RECRUITING

Exelixis Clinical Site #31

Salzburg, 5020, Austria

COMPLETED

Exelixis Clinical Site #29

Vienna, 1020, Austria

RECRUITING

Exelixis Clinical Site #106

Wein, 1090, Austria

RECRUITING

Exelixis Clinical Site #39

Anderlecht, 1070, Belgium

RECRUITING

Exelixis Clinical Site #37

Kortrijk, 8500, Belgium

RECRUITING

Exelixis Clinical Site #85

Besançon, 25030, France

RECRUITING

Exelixis Clinical Site #96

Bordeaux, 33000, France

RECRUITING

Exelixis Clinical Site #79

Caen, 14076, France

RECRUITING

Exelixis Clinical Site #118

Clermont-Ferrand, 63011, France

RECRUITING

Exelixis Clinical Site #109

Lyon, 69008, France

WITHDRAWN

Exelixis Clinical Site #92

Marseille, 13273, France

RECRUITING

Exelixis Clinical Site #64

Nice, 06189, France

RECRUITING

Exelixis Clinical Site #83

Paris, 75010, France

RECRUITING

Exelixis Clinical Site #91

Paris, 75015, France

WITHDRAWN

Exelixis Clinical Site #80

Rennes, 35042, France

RECRUITING

Exelixis Clinical Site #63

Saint-Herblain, 44805, France

RECRUITING

Exelixis Clinical Site #75

Strasbourg, 67200, France

RECRUITING

Exelixis Clinical Site #84

Vandœuvre-lès-Nancy, 54519, France

RECRUITING

Exelixis Clinical Site #115

Villejuif, 94805, France

RECRUITING

Exelixis Clinical Site #103

Essen, 45147, Germany

RECRUITING

Exelixis Clinical Site #113

Hamburg, 22763, Germany

RECRUITING

Exelixis Clinical Site #108

Heidelberg, 69120, Germany

RECRUITING

Exelixis Clinical Site #82

Herne, 44625, Germany

RECRUITING

Exelixis Clinical Site #93

Jena, 07747, Germany

RECRUITING

Exelixis Clinical Site #112

München, 81737, Germany

COMPLETED

Exelixis Clinical Site #102

Nürtingen, 72622, Germany

RECRUITING

Exelixis Clinical Site #107

Trier, 54292, Germany

RECRUITING

Exelixis Clinical Site #95

Tübingen, 72076, Germany

RECRUITING

Exelixis Clinical Site #86

Beersheba, 8410101, Israel

RECRUITING

Exelixis Clinical Site #72

Haifa, 3109601, Israel

RECRUITING

Exelixis Clinical Site #52

Jerusalem, 9112001, Israel

RECRUITING

Exelixis Clinical Site #71

Petah Tikva, 4941492, Israel

RECRUITING

Exelixis Clinical Site #69

Tel Aviv, 6423906, Israel

RECRUITING

Exelixis Clinical Site #38

Ẕerifin, 7030000, Israel

RECRUITING

Exelixis Clinical Site #121

Ancona, 60020, Italy

RECRUITING

Exelixis Clinical Site #117

Bologna, 40138, Italy

RECRUITING

Exelixis Clinical Site #90

Florence, 50134, Italy

RECRUITING

Exelixis Clinical Site #101

Milan, 20132, Italy

RECRUITING

Exelixis Clinical Site #81

Milan, 20141, Italy

RECRUITING

Exelixis Clinical Site #40

Naples, 80131, Italy

RECRUITING

Exelixis Clinical Site #74

Ravenna, 48121, Italy

RECRUITING

Exelixis Clinical Site #30

Grafton, 1023, New Zealand

RECRUITING

Exelixis Clinical Site #45

Hamilton, 3204, New Zealand

RECRUITING

Exelixis Clinical Site #20

Bydgoszcz, 85-796, Poland

RECRUITING

Exelixis Clinical Site #28

Gdansk, 80-219, Poland

RECRUITING

Exelixis Clinical Site #34

Otwock, 05-400, Poland

RECRUITING

Exelixis Clinical Site #54

Poznan, 60-569, Poland

RECRUITING

Exelixis Clinical Site #114

Wroclaw, 53-413, Poland

RECRUITING

Exelixis Clinical Site #41

Badajoz, 06080, Spain

RECRUITING

Exelixis Clinical Site #53

Barcelona, 08035, Spain

RECRUITING

Exelixis Clinical Site #15

Barcelona, 08036, Spain

RECRUITING

Exelixis Clinical Site #27

Barcelona, 08041, Spain

RECRUITING

Exelixis Clinical Site #120

L'Hospitalet de Llobregat, 08908, Spain

RECRUITING

Exelixis Clinical Site #57

Madrid, 28033, Spain

RECRUITING

Exelixis Clinical Site #43

Madrid, 28034, Spain

RECRUITING

Exelixis Clinical Site #58

Madrid, 28040, Spain

RECRUITING

Exelixis Clinical Site #77

Madrid, 28040, Spain

RECRUITING

Exelixis Clinical Site #19

Madrid, 28041, Spain

RECRUITING

Exelixis Clinical Site #100

Madrid, 28046, Spain

RECRUITING

Exelixis Clinical Site #18

Pamplona, 31008, Spain

RECRUITING

Exelixis Clinical Site #119

Santander, 39008, Spain

RECRUITING

Exelixis Clinical Site #23

Seville, 41013, Spain

RECRUITING

Exelixis Clinical Site #56

Valencia, 46010, Spain

RECRUITING

Exelixis Clinical Site #25

Valencia, 46026, Spain

RECRUITING

Exelixis Clinical Site #21

Chur, 7000, Switzerland

COMPLETED

Exelixis Clinical Site #22

Sankt Gallen, 9007, Switzerland

RECRUITING

Exelixis Clinical Site #44

Winterthur, 8401, Switzerland

RECRUITING

Exelixis Clinical Site #110

Cambridge, CB2 0QQ, United Kingdom

RECRUITING

Exelixis Clinical Site #99

London, W6 8RF, United Kingdom

RECRUITING

Exelixis Clinical Site #97

Middlesex, HA6 2RN, United Kingdom

RECRUITING

MeSH Terms

Conditions

Carcinoma, Renal Cell; Carcinoma, Transitional Cell; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

Nivolumab; Ipilimumab; relatlimab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Liver Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma, Squamous Cell; Head and Neck Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Medical Director

  Exelixis

  STUDY DIRECTOR

Central Study Contacts

Exelixis Clinical Trials

CONTACT

1-888-EXELIXIS (888-393-5494); druginfo@exelixis.com

Backup or International

CONTACT

650-837-7400

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose-escalation followed by expansion phase with parallel assignment.

Study Record Dates

• First Submitted: December 15, 2021
• First Posted: January 4, 2022
• Study Start: December 14, 2021
• Primary Completion (Estimated): June 28, 2030
• Study Completion (Estimated): June 28, 2030
• Last Updated: March 12, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

AU (4); IL (6); PL (5); NZ (2); BE (2); FR (14); CH (3); DE (9); IT (7); ES (16); US (46); GB (3)