New drug combo aims to shrink hard-to-treat tumors
NCT ID NCT05176483
First seen Jun 27, 2026 · Last updated Aug 06, 2026 · Updated 2 times
Summary
This study tests a new drug called zanzalintinib, alone or with other immune-boosting drugs, in people with advanced solid tumors that have stopped responding to standard treatments. The goal is to find safe doses and see if the combination can shrink tumors or slow their growth. About 1,300 participants with various cancers, including kidney, prostate, and lung cancer, will take part.
This is an AI summary of the original study and may miss details. Read our disclaimer.
Study facts
What this study's own registry entry says, in plain language.
- Phase
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Phase 1
The first testing in people. Mainly checks safety and dose, usually in a small group.
- Participants
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About 1,394 people
The number the study aims to enrol. It can still change while the study runs.
- Started
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Dec 2021
- Expected to finish
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Jun 2030
An estimate. End dates often move.
- Lead sponsor
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A company
The lead sponsor is a pharmaceutical, biotech, or medical-device company.
Who can take part
This study's own entry requirements. Only the study team can say for certain whether you qualify.
- Ages
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18 years and older
- Sex
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Anyone
- Healthy volunteers
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Not accepted
This study is not open to healthy volunteers. The entry requirements below say who it is open to.
Show the full entry requirements Hide the full entry requirements
Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.
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.
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Conditions
The condition(s) this trial relates to.
As listed by the trial registrant
The condition terms exactly as the trial's registrant entered them.
How to take part
Only the study team decides who joins. These are the ways to reach them.
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The study's own enquiry address
This study publishes an address for enquiries. See it below .
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The places running it
114 sites in 13 countries. The list below names each one and where it is.
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The official record
ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.
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A doctor treating you
A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.
Contacts and locations
Show contact details
Enter your email to view the contact information for this study.
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Study contacts
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Contact
Email: •••••@•••••
Locations
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Exelixis Clinical Site #1
RECRUITINGTucson, Arizona, 85711, United States
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Exelixis Clinical Site #10
RECRUITINGCleveland, Ohio, 44106, United States
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Exelixis Clinical Site #100
RECRUITINGMadrid, 28046, Spain
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Exelixis Clinical Site #101
RECRUITINGMilan, 20132, Italy
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Exelixis Clinical Site #102
RECRUITINGNürtingen, 72622, Germany
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Exelixis Clinical Site #103
RECRUITINGEssen, 45147, Germany
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Exelixis Clinical Site #104
RECRUITINGHershey, Pennsylvania, 17033, United States
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Exelixis Clinical Site #105
RECRUITINGHackensack, New Jersey, 07601, United States
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Exelixis Clinical Site #106
RECRUITINGWein, 1090, Austria
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Exelixis Clinical Site #107
RECRUITINGTrier, 54292, Germany
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Exelixis Clinical Site #108
RECRUITINGHeidelberg, 69120, Germany
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Exelixis Clinical Site #109
WITHDRAWNLyon, 69008, France
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Exelixis Clinical Site #11
RECRUITINGGainesville, Florida, 32610, United States
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Exelixis Clinical Site #110
RECRUITINGCambridge, CB2 0QQ, United Kingdom
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Exelixis Clinical Site #111
RECRUITINGDallas, Texas, 75246, United States
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Exelixis Clinical Site #112
COMPLETEDMünchen, 81737, Germany
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Exelixis Clinical Site #113
RECRUITINGHamburg, 22763, Germany
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Exelixis Clinical Site #114
RECRUITINGWroclaw, 53-413, Poland
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Exelixis Clinical Site #115
RECRUITINGVillejuif, 94805, France
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Exelixis Clinical Site #116
RECRUITINGAlbury, 2640, Australia
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Exelixis Clinical Site #117
RECRUITINGBologna, 40138, Italy
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Exelixis Clinical Site #118
RECRUITINGClermont-Ferrand, 63011, France
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Exelixis Clinical Site #119
RECRUITINGSantander, 39008, Spain
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Exelixis Clinical Site #12
RECRUITINGDurham, North Carolina, 27710, United States
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Exelixis Clinical Site #120
RECRUITINGL'Hospitalet de Llobregat, 08908, Spain
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Exelixis Clinical Site #121
RECRUITINGAncona, 60020, Italy
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Exelixis Clinical Site #122
RECRUITINGLouisville, Kentucky, 40202, United States
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Exelixis Clinical Site #123
RECRUITINGPalo Alto, California, 94304, United States
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Exelixis Clinical Site #13
RECRUITINGDetroit, Michigan, 48202, United States
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Exelixis Clinical Site #14
RECRUITINGBaltimore, Maryland, 21201, United States
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Exelixis Clinical Site #15
RECRUITINGBarcelona, 08036, Spain
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Exelixis Clinical Site #16
RECRUITINGBrisbane, 4102, Australia
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Exelixis Clinical Site #18
RECRUITINGPamplona, 31008, Spain
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Exelixis Clinical Site #19
RECRUITINGMadrid, 28041, Spain
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Exelixis Clinical Site #2
RECRUITINGOmaha, Nebraska, 68130, United States
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Exelixis Clinical Site #20
RECRUITINGBydgoszcz, 85-796, Poland
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Exelixis Clinical Site #21
COMPLETEDChur, 7000, Switzerland
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Exelixis Clinical Site #22
RECRUITINGSankt Gallen, 9007, Switzerland
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Exelixis Clinical Site #23
RECRUITINGSeville, 41013, Spain
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Exelixis Clinical Site #24
RECRUITINGPittsburgh, Pennsylvania, 15232, United States
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Exelixis Clinical Site #25
RECRUITINGValencia, 46026, Spain
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Exelixis Clinical Site #26
RECRUITINGChicago, Illinois, 60612, United States
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Exelixis Clinical Site #27
RECRUITINGBarcelona, 08041, Spain
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Exelixis Clinical Site #28
RECRUITINGGdansk, 80-219, Poland
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Exelixis Clinical Site #29
RECRUITINGVienna, 1020, Austria
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Exelixis Clinical Site #3
RECRUITINGNashville, Tennessee, 37203, United States
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Exelixis Clinical Site #30
RECRUITINGGrafton, 1023, New Zealand
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Exelixis Clinical Site #31
COMPLETEDSalzburg, 5020, Austria
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Exelixis Clinical Site #32
RECRUITINGPittsburgh, Pennsylvania, 15212, United States
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Exelixis Clinical Site #33
RECRUITINGMilwaukee, Wisconsin, 53226, United States
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Exelixis Clinical Site #34
RECRUITINGOtwock, 05-400, Poland
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Exelixis Clinical Site #35
RECRUITINGBirtinya, 4575, Australia
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Exelixis Clinical Site #36
RECRUITINGSydney, 2109, Australia
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Exelixis Clinical Site #37
RECRUITINGKortrijk, 8500, Belgium
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Exelixis Clinical Site #38
RECRUITINGẔerifin, 7030000, Israel
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Exelixis Clinical Site #39
COMPLETEDAnderlecht, 1070, Belgium
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Exelixis Clinical Site #4
RECRUITINGIndianapolis, Indiana, 46250, United States
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Exelixis Clinical Site #40
RECRUITINGNaples, 80131, Italy
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Exelixis Clinical Site #41
RECRUITINGBadajoz, 06080, Spain
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Exelixis Clinical Site #42
RECRUITINGSaint Leonards, 2065, Australia
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Exelixis Clinical Site #43
RECRUITINGMadrid, 28034, Spain
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Exelixis Clinical Site #44
RECRUITINGWinterthur, 8401, Switzerland
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Exelixis Clinical Site #45
RECRUITINGHamilton, 3204, New Zealand
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Exelixis Clinical Site #46
RECRUITINGAustin, Texas, 78705, United States
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Exelixis Clinical Site #47
RECRUITINGMiami, Florida, 33136, United States
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Exelixis Clinical Site #48
RECRUITINGCelebration, Florida, 34747, United States
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Exelixis Clinical Site #49
ACTIVE_NOT_RECRUITINGNewark, Delaware, 19713, United States
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Exelixis Clinical Site #5
ACTIVE_NOT_RECRUITINGOmaha, Nebraska, 68130, United States
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Exelixis Clinical Site #50
RECRUITINGPlano, Texas, 75075, United States
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Exelixis Clinical Site #51
RECRUITINGPortland, Oregon, 97239, United States
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Exelixis Clinical Site #52
RECRUITINGJerusalem, 9112001, Israel
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Exelixis Clinical Site #53
RECRUITINGBarcelona, 08035, Spain
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Exelixis Clinical Site #54
RECRUITINGPoznan, 60-569, Poland
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Exelixis Clinical Site #55
RECRUITINGLas Vegas, Nevada, 89052, United States
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Exelixis Clinical Site #56
RECRUITINGValencia, 46010, Spain
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Exelixis Clinical Site #57
RECRUITINGMadrid, 28033, Spain
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Exelixis Clinical Site #58
RECRUITINGMadrid, 28040, Spain
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Exelixis Clinical Site #59
RECRUITINGSanta Barbara, California, 93463, United States
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Exelixis Clinical Site #6
RECRUITINGNew York, New York, 10065, United States
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Exelixis Clinical Site #60
RECRUITINGNew York, New York, 10032, United States
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Exelixis Clinical Site #61
RECRUITINGPlantation, Florida, 33322, United States
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Exelixis Clinical Site #62
RECRUITINGNew Haven, Connecticut, 06510, United States
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Exelixis Clinical Site #63
RECRUITINGSaint-Herblain, 44805, France
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Exelixis Clinical Site #64
RECRUITINGNice, 06189, France
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Exelixis Clinical Site #65
RECRUITINGDetroit, Michigan, 48201, United States
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Exelixis Clinical Site #66
RECRUITINGCharlottesville, Virginia, 22903, United States
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Exelixis Clinical Site #67
RECRUITINGPhoenix, Arizona, 85054, United States
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Exelixis Clinical Site #68
RECRUITINGRochester, Minnesota, 55905, United States
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Exelixis Clinical Site #69
RECRUITINGTel Aviv, 6423906, Israel
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Exelixis Clinical Site #7
RECRUITINGBoston, Massachusetts, 02215, United States
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Exelixis Clinical Site #70
RECRUITINGTyler, Texas, 75601, United States
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Exelixis Clinical Site #71
RECRUITINGPetah Tikva, 4941492, Israel
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Exelixis Clinical Site #72
RECRUITINGHaifa, 3109601, Israel
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Exelixis Clinical Site #73
RECRUITINGIrving, Texas, 75063, United States
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Exelixis Clinical Site #74
RECRUITINGRavenna, 48121, Italy
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Exelixis Clinical Site #75
RECRUITINGStrasbourg, 67200, France
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Exelixis Clinical Site #76
RECRUITINGSyracuse, New York, 13210, United States
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Exelixis Clinical Site #77
RECRUITINGMadrid, 28040, Spain
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Exelixis Clinical Site #78
RECRUITINGJacksonville, Florida, 32224, United States
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Exelixis Clinical Site #79
RECRUITINGCaen, 14076, France
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Exelixis Clinical Site #8
RECRUITINGTampa, Florida, 33612, United States
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Exelixis Clinical Site #80
RECRUITINGRennes, 35042, France
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Exelixis Clinical Site #81
RECRUITINGMilan, 20141, Italy
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Exelixis Clinical Site #82
RECRUITINGHerne, 44625, Germany
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Exelixis Clinical Site #83
RECRUITINGParis, 75010, France
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Exelixis Clinical Site #84
RECRUITINGVandœuvre-lès-Nancy, 54519, France
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Exelixis Clinical Site #85
RECRUITINGBesançon, 25030, France
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Exelixis Clinical Site #86
RECRUITINGBeersheba, 8410101, Israel
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Exelixis Clinical Site #87
RECRUITINGLittleton, Colorado, 80124, United States
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Exelixis Clinical Site #88
RECRUITINGEast Brunswick, New Jersey, 08816, United States
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Exelixis Clinical Site #89
RECRUITINGDallas, Texas, 75246, United States
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Exelixis Clinical Site #9
RECRUITINGMyrtle Beach, South Carolina, 29572, United States
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Exelixis Clinical Site #90
RECRUITINGFlorence, 50134, Italy
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Exelixis Clinical Site #91
WITHDRAWNParis, 75015, France
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Exelixis Clinical Site #92
RECRUITINGMarseille, 13273, France
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Exelixis Clinical Site #93
RECRUITINGJena, 07747, Germany
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Exelixis Clinical Site #94
RECRUITINGGraz, 8036, Austria
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Exelixis Clinical Site #95
RECRUITINGTübingen, 72076, Germany
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Exelixis Clinical Site #96
RECRUITINGBordeaux, 33000, France
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Exelixis Clinical Site #97
RECRUITINGMiddlesex, HA6 2RN, United Kingdom
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Exelixis Clinical Site #98
RECRUITINGPhiladelphia, Pennsylvania, 19104, United States
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Exelixis Clinical Site #99
RECRUITINGLondon, W6 8RF, United Kingdom
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