BridgeMD
New treatment option for Renal Cell Carcinoma (RCC)
Official title Study of Zanzalintinib in Combination With Immuno-Oncology Agents in Participants With Solid Tumors
ClinicalTrials.gov ID: NCT05176483
What this study is testing
What is Zanzalintinib?
Zanzalintinib is an investigational medicine, given as an once-daily pill taken by mouth, being studied as a potential treatment for renal cell carcinoma (rcc).
Also referred to as XL092.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- 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.
- Phase 1: an early, usually small safety study
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join 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...
- Expansion Cohort 1 (ccRCC): Participants with unresectable advanced or metastatic RCC with a clear cell component who have not received prior...
- Note: Prior non-vascular endothelial growth factor (VEGF) targeted adjuvant or neoadjuvant is allowed if disease recurrence occurred 6 months after...
- Expansion Cohort 2 (ccRCC): Participants with unresectable advanced or metastatic RCC with a clear cell component.
You likely can't join if
- For all Dose-Escalation cohorts: Prior treatment with zanzalintinib. For all Expansion Cohorts: Prior treatment with zanzalintinib, nivolumab...
- 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...
- For Cohort 3 (mCRPC): Receipt of abiraterone within 1 week; cyproterone within 10 days; or receipt of flutamide, nilutamide, bicalutamide...
- 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...
- Any complementary medications (eg, herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks before first...
- Prior external radiation therapy for bone metastasis within 2 weeks, for other tumor sites within 4 weeks, and prior radium-223 therapy within 6...
See the full eligibility criteria
Who can join
- 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...
- 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...
- 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...
- 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...
- 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...
- 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...
- 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
What rules you out
- 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...
- 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...
- 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...
- 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...
- 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...
- 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...
- 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). Note: Additional Inclusion and Exclusion criteria may apply.
The study team makes the final eligibility decision.
Where it's taking place
- Phoenix, Arizona, United States
- Tucson, Arizona, United States
- Palo Alto, California, United States
- Santa Barbara, California, United States
- Littleton, Colorado, United States
- New Haven, Connecticut, United States
- Newark, Delaware, United States
- Celebration, Florida, United States
- Gainesville, Florida, United States
- Jacksonville, Florida, United States
- Miami, Florida, United States
- Plantation, Florida, United States
- Tampa, Florida, United States
- Chicago, Illinois, United States
- Indianapolis, Indiana, United States
- Louisville, Kentucky, United States
- Baltimore, Maryland, United States
- Boston, Massachusetts, United States
- Detroit, Michigan, United States
- Rochester, Minnesota, United States
+ 87 more site(s).
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Phoenix, Arizona, United States; Tucson, Arizona, United States; Palo Alto, California, United States; Santa Barbara, California, United States; Littleton, Colorado, United States; New Haven, Connecticut, United States and 101 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.