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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) and nivolumab + ipilimumab (triplet) and nivolumab + relatlimab fixed-dose combination (FDC) (triplet) in subjects with advanced solid tumors.
EU CTIS ID: 2023-510061-10-00
What this study is testing
The objectives of the Dose-Escalation Stage are to determine the recommended dose (RD) and evaluate the safety, tolerability, pharmacokinetics, immunogenicity, and pharmacodynamics of zanzalintinib in combination with the immuno-oncology agents nivolumab (doublet), nivolumab + ipilimumab (triplet), and nivolumab + relatlimab FDC (triplet) in participants with advanced cancers. The objectives of the Expansion Stage are to assess the preliminary efficacy of zanzalintinib alone and in combination therapy regimens in tumor specific cohorts, determine the safety of the combination therapy regimens, isolate the contribution of treatment components, and further evaluate the plasma pharmacokinetics of daily oral XL092 administered as a single agent or in combination therapy in participants with advanced solid tumors.
- Human Pharmacology (Phase I)- Other
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- 1. Cytologically or histologically confirmed solid tumor that is unresectable, locally advanced or metastatic: Dose-Escalation Stage: a. 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 Stage: The tumor cohorts are: Cohort 1: ccRCC (1L); Cohort 2: ccRCC (2L); Cohort 3: mCRPC (post 1 NHT); Cohort 4: UC ICI-naïve; Cohort 5: UC (post EV and ICI); Cohort 6: nccRCC (1L); Cohort 7: HCC (1L); Cohort 8: NSCLC (PD-L1 low TPS 149%, 1L); Cohort 9: NSCLC (2L+; Cohort 10: CRC (MSS, 2L or 3L and beyond); Cohort 11: HNSCC (ICI-naïve); Cohort 12: ccRCC (2-3L); Cohort 13 and Cohort 14: ccRCC (1L) - please refer to protocol for additional details on inclusion criteria for specific Cohorts.
- 10. Female participants of childbearing potential must not be pregnant at screening.
- 2. For all expansion cohorts except Cohort 3 measurable disease per RECIST 1.1 (Eisenhauer et al 2009) as determined by the Investigator with exception of mCRPC.
- 3. For expansion cohorts 1-11 only: archival tumor tissue material, if available, or fresh tumor tissue if it can be safely obtained.
- 4. Recovery to baseline or ≤ Grade 1 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.
- 5. Age 18 years or older on the day of consent.
You likely can't join if
- 1. For all Dose-Escalation Cohorts: Prior treatment with zanzalintinib. For all Expansion Cohorts: Prior treatment with zanzalintinib, nivolumab, ipilimumab, or relatlimab with some exceptions.
- 10. Uncontrolled, significant intercurrent or recent illness.
- 11. Major surgery within 8 weeks prior to first dose. Prior laparoscopic nephrectomy within 4 weeks prior to first dose. Minor surgery (eg, simple excision, tooth extraction) within 10 days before first dose of study treatment. Complete wound healing from major or minor surgery must have occurred at least prior to first dose.
- 12. Corrected QT interval calculated by the Fridericia formula (QTcF) 460 ms for females and > 450 ms for male per electrocardiogram (ECG) within 14 days before first dose of study treatment. Furthermore, participants must not have family history of sudden cardiac death before age 50, heart disease, history of arrhythmia, bradycardia defined as < 50 beats per minute, or acute neurologic events within 6 months prior to inclusion.
- 13. Participants with inadequately treated adrenal insufficiency.
- 14. History of psychiatric illness likely to interfere with ability to comply with protocol requirements or give informed consent
See the full eligibility criteria
Who can join
- 1. Cytologically or histologically confirmed solid tumor that is unresectable, locally advanced or metastatic: Dose-Escalation Stage: a. 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 Stage: The tumor cohorts are: Cohort 1: ccRCC (1L); Cohort 2: ccRCC (2L); Cohort 3: mCRPC (post 1 NHT); Cohort 4: UC ICI-naïve; Cohort 5: UC (post EV and ICI); Cohort 6: nccRCC (1L); Cohort 7: HCC (1L); Cohort 8: NSCLC (PD-L1 low TPS 149%, 1L); Cohort 9: NSCLC (2L+; Cohort 10: CRC (MSS, 2L or 3L and beyond); Cohort 11: HNSCC (ICI-naïve); Cohort 12: ccRCC (2-3L); Cohort 13 and Cohort 14: ccRCC (1L) - please refer to protocol for additional details on inclusion criteria for specific Cohorts.
- 10. Female participants of childbearing potential must not be pregnant at screening.
- 2. For all expansion cohorts except Cohort 3 measurable disease per RECIST 1.1 (Eisenhauer et al 2009) as determined by the Investigator with exception of mCRPC.
- 3. For expansion cohorts 1-11 only: archival tumor tissue material, if available, or fresh tumor tissue if it can be safely obtained.
- 4. Recovery to baseline or ≤ Grade 1 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.
- 5. Age 18 years or older on the day of consent.
- 6. Karnofsky Performance Status (KPS) ≥ 70%.
- 7. Adequate organ and marrow function.
- 8. Capable of understanding and complying with the protocol requirements and must have signed the ICF.
- 9. Sexually active fertile participants and their partners must agree to use highly effective methods of contraception during the course of the study and for the following durations after the last dose of treatment (whichever is later).
What rules you out
- 1. For all Dose-Escalation Cohorts: Prior treatment with zanzalintinib. For all Expansion Cohorts: Prior treatment with zanzalintinib, nivolumab, ipilimumab, or relatlimab with some exceptions.
- 10. Uncontrolled, significant intercurrent or recent illness.
- 11. Major surgery within 8 weeks prior to first dose. Prior laparoscopic nephrectomy within 4 weeks prior to first dose. Minor surgery (eg, simple excision, tooth extraction) within 10 days before first dose of study treatment. Complete wound healing from major or minor surgery must have occurred at least prior to first dose.
- 12. Corrected QT interval calculated by the Fridericia formula (QTcF) 460 ms for females and > 450 ms for male per electrocardiogram (ECG) within 14 days before first dose of study treatment. Furthermore, participants must not have family history of sudden cardiac death before age 50, heart disease, history of arrhythmia, bradycardia defined as < 50 beats per minute, or acute neurologic events within 6 months prior to inclusion.
- 13. Participants with inadequately treated adrenal insufficiency.
- 14. History of psychiatric illness likely to interfere with ability to comply with protocol requirements or give informed consent
- 15. Pregnant or lactating females.
- 16. Inability to swallow tablets or ingest a suspension either orally or by a nasogastric or gastrostomy tube.
- 17. Previously identified allergy or hypersensitivity to components of the study treatment formulations or history of severe infusion-related reactions (IRRs) to monoclonal antibodies.
- 18. 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.
- 19. Other conditions, which in the opinion of the investigator or Sponsor, would compromise the safety of the subject’s ability to complete the study. Please refer to the protocol for detailed cohort specific exclusion criteria.
- 2. For Dose-Escalation Cohorts and Cohort 2 (ccRCC 2L), Cohort 3 (mCRPC), Cohort 5 (UC), Cohort 9 (NSCLC, 2L+), Cohort 10 (CRC, 2L or 3L or beyond) and Cohort 12 (ccRCC 2-3L): Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
- 3. 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.
- 4. For all Dose-Escalation Cohorts and Cohort 2 (ccRCC 2L), Cohort 3 (mCRPC), Cohort 5 (UC), Cohort 9 (NSCLC (2L+), Cohort 10 (CRC, 2L or 3L and beyond), and Cohort 12 (ccRCC 2-3L): Receipt of any type of anticancer antibody (including investigational antibody) or systemic chemotherapy within 4 weeks before first dose of study treatment.
- 5. 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.
- 6. Prior 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.
- 7. 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.
- 8. Concomitant anticoagulation with oral anticoagulants with some exceptions (refer to protocol)
- 9. Administration of a live, attenuated vaccine 30 days prior to first dose.
The study team makes the final eligibility decision.
Where it's taking place
- United Kingdom
- Israel
- New Zealand
- Switzerland
- Australia
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, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include United Kingdom; Israel; New Zealand; Switzerland; Australia. Enter your location above to see the nearest site and check your eligibility.
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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.