Informations générales (source: ClinicalTrials.gov)
A Dose-Escalation and Expansion Study of the Safety and Efficacy of XL092 in Combination With Immuno-Oncology Agents in Subjects With Unresectable Advanced or Metastatic Solid Tumors
Interventional
Phase 1
Exelixis (Voir sur ClinicalTrials)
décembre 2021
juin 2030
02 mars 2026
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.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Yohann LORIOT | 10/06/2024 09:58:10 | Contacter | ||
Critères
Tous
- 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.
- 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 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.
- 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).
Note: Additional Inclusion and Exclusion criteria may apply.