Study of Zanzalintinib in Combination With Immuno-Oncology or Other Agents in Participants With Solid Tumors
A Dose-Escalation and Expansion Study of the Safety and Efficacy of XL092 in Combination With Immuno-Oncology or Other Agents in Subjects With Unresectable Advanced or Metastatic Solid Tumors
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 18 Years and older
- Sex
- All sexes
- Healthy volunteers
- Not accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
Not stated in the study description — ask the study team about visits and procedures.
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This study tests zanzalintinib alone or with other cancer drugs in people with advanced solid tumors. It looks at safety, how the body handles the drugs, and whether treatment helps fight cancer. One group also tests how zanzalintinib affects other medicines.
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) and in combination with docetaxel and prednisone in participants with advanced solid tumors. In addition, the study will evaluate the effect of multiple dose administration of zanzalintinib on the single-dose pharmacokinetics of sensitive CYP3A4, CYP2C9, CYP2C19, or CYP1A2 substrates 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.
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- Have a solid tumor confirmed by a tissue or cell test that cannot be removed by surgery, has grown nearby, or has spread.
- For dose-testing and drug-interaction groups, treatments that extend life must be unavailable, too hard to tolerate, or no longer working. The drug-interaction group must be able to swallow pills.
- Cancer-specific groups include certain kidney, prostate, urinary tract, liver, lung, colon, rectal, and head or neck cancers. Each group has its own rules about cancer type, past treatment, and tumor test results.
- Most cancer-specific groups need tumors that can be measured on scans. Groups 1–11 also need stored tumor tissue, if available, or a new sample if it can be taken safely.
- Side effects from past treatment must have mostly gone away, unless the study doctor finds them minor or stable with care.
- Be able to care for yourself, even if you cannot work or do normal activities. The required activity score is at least 70%.
- Have organs and bone marrow that work well enough. Bone marrow makes blood cells.
- If able to become pregnant, you must not be pregnant at screening. Sexually active participants who can have children and their partners must use highly effective birth control.
Who can't join
- Past zanzalintinib treatment is not allowed. Some groups also bar past nivolumab, ipilimumab, or relatlimab, but there are exceptions.
- Certain recent cancer drugs are not allowed in some groups. Waiting times range from 1 to 4 weeks, depending on the drug and group.
- Herbal products or traditional medicines used to treat the cancer within 2 weeks before study treatment are not allowed.
- Recent radiation treatment is not allowed unless an exception applies: within 2 weeks for cancer in bones, 4 weeks for other sites, or 6 weeks for radium-223.
- Cancer in the brain or the space around the brain's outer covering is not allowed unless treated and stable for at least 4 weeks before study treatment.
- Blood thinners taken by mouth are not allowed, except certain drugs called direct factor Xa inhibitors.
- There is a restriction on live, weakened vaccines within 30 days, but the provided text cuts off before the full rule.
Simplified for readability. The official criteria below are what the study team uses.
Official eligibility criteria
Key Inclusion Criteria: * 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. * 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. * Cohort 15 (mCRPC, post-ARPI, visceral metastases): Men with metastatic adenocarcinoma of the prostate. * Cohort 16 (Drug-drug interaction \[DDI\]): * 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. * Able to swallow capsules or tablets. * 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. Key Exclusion Criteria: * 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 cytotoxic 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. * 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). * For Cohort 16 (DDI): * Known hypersensitivity to midazolam, warfarin, omeprazole, or caffeine. * History of major head trauma (with loss of consciousness) within the past year or minor head trauma (without loss of consciousness) within 3 months prior to first dose of study treatment on Day 1. * Primary liver tumor. * Unable to refrain from or anticipates the use of the following: * Any drugs known to be inducers or inhibitors of CYP3A4, CYP2C9, CYP2C19, and/or CYP1A2 within 14 days before the first dose of study treatment on Day 1 through the DDI assessments on Day 20. * Drugs that are contraindicated with midazolam, warfarin, omeprazole, and/or caffeine during the DDI assessment part. * Caffeine-containing beverages, products, and foods at least 3 days prior to and 3 days after probe substrate cocktail administration on Day 1 and Day 16. * Poor peripheral venous access. Note: Additional Inclusion and Exclusion criteria may apply.
Study sites (46)
AZ
- Exelixis Clinical Site #67 · Phoenix, AZ 85054More trials in Phoenix
- Exelixis Clinical Site #1 · Tucson, AZ 85711More trials in Tucson
CA
- Exelixis Clinical Site #123 · Palo Alto, CA 94304More trials in Palo Alto
- Exelixis Clinical Site #59 · Santa Barbara, CA 93463More trials in Santa Barbara
CO
- Exelixis Clinical Site #87 · Littleton, CO 80124More trials in Littleton
CT
- Exelixis Clinical Site #62 · New Haven, CT 06510More trials in New Haven
DE
- Exelixis Clinical Site #49 · Newark, DE 19713More trials in Newark
FL
- Exelixis Clinical Site #48 · Celebration, FL 34747More trials in Celebration
- Exelixis Clinical Site #11 · Gainesville, FL 32610More trials in Gainesville
- Exelixis Clinical Site #78 · Jacksonville, FL 32224More trials in Jacksonville
- Exelixis Clinical Site #47 · Miami, FL 33136More trials in Miami
- Exelixis Clinical Site #61 · Plantation, FL 33322More trials in Plantation
- Exelixis Clinical Site #8 · Tampa, FL 33612More trials in Tampa
IL
- Exelixis Clinical Site #26 · Chicago, IL 60612More trials in Chicago
IN
- Exelixis Clinical Site #4 · Indianapolis, IN 46250More trials in Indianapolis
KY
- Exelixis Clinical Site #122 · Louisville, KY 40202More trials in Louisville
MA
- Exelixis Clinical Site #7 · Boston, MA 02215More trials in Boston
MD
- Exelixis Clinical Site #14 · Baltimore, MD 21201More trials in Baltimore
MI
- Exelixis Clinical Site #65 · Detroit, MI 48201More trials in Detroit
- Exelixis Clinical Site #13 · Detroit, MI 48202More trials in Detroit
MN
- Exelixis Clinical Site #68 · Rochester, MN 55905More trials in Rochester
NC
- Exelixis Clinical Site #12 · Durham, NC 27710More trials in Durham
NE
- Exelixis Clinical Site #2 · Omaha, NE 68130More trials in Omaha
- Exelixis Clinical Site #5 · Omaha, NE 68130More trials in Omaha
NJ
- Exelixis Clinical Site #88 · East Brunswick, NJ 08816More trials in East Brunswick
- Exelixis Clinical Site #105 · Hackensack, NJ 07601More trials in Hackensack
NV
- Exelixis Clinical Site #55 · Las Vegas, NV 89052More trials in Las Vegas
NY
- Exelixis Clinical Site #60 · New York, NY 10032More trials in New York
- Exelixis Clinical Site #6 · New York, NY 10065More trials in New York
- Exelixis Clinical Site #76 · Syracuse, NY 13210More trials in Syracuse
OH
- Exelixis Clinical Site #10 · Cleveland, OH 44106More trials in Cleveland
OR
- Exelixis Clinical Site #51 · Portland, OR 97239More trials in Portland
PA
- Exelixis Clinical Site #104 · Hershey, PA 17033More trials in Hershey
- Exelixis Clinical Site #98 · Philadelphia, PA 19104More trials in Philadelphia
- Exelixis Clinical Site #32 · Pittsburgh, PA 15212More trials in Pittsburgh
- Exelixis Clinical Site #24 · Pittsburgh, PA 15232More trials in Pittsburgh
SC
- Exelixis Clinical Site #9 · Myrtle Beach, SC 29572More trials in Myrtle Beach
TN
- Exelixis Clinical Site #3 · Nashville, TN 37203More trials in Nashville
TX
- Exelixis Clinical Site #46 · Austin, TX 78705More trials in Austin
- Exelixis Clinical Site #111 · Dallas, TX 75246More trials in Dallas
- Exelixis Clinical Site #89 · Dallas, TX 75246More trials in Dallas
- Exelixis Clinical Site #73 · Irving, TX 75063More trials in Irving
- Exelixis Clinical Site #50 · Plano, TX 75075More trials in Plano
- Exelixis Clinical Site #70 · Tyler, TX 75601More trials in Tyler
VA
- Exelixis Clinical Site #66 · Charlottesville, VA 22903More trials in Charlottesville
WI
- Exelixis Clinical Site #33 · Milwaukee, WI 53226More trials in Milwaukee