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
04 septembre 2025
This is a multicenter Phase 1b, open label, dose-escalation and cohort-expansion study,
evaluating the safety, tolerability, PK, preliminary antitumor activity, and effect of
biomarkers of XL092 administered alone, and in combination with nivolumab (doublet),
nivolumab + ipilimumab (triplet) and nivolumab + relatlimab (triplet) in subjects with
advanced solid tumors.
In the Expansion Stage, the safety and efficacy of XL092 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 | ||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Exelixis Clinical Site #109 - 69008 - Lyon - France | Contact (sur clinicalTrials) | ||||
| Exelixis Clinical Site #115 - 94805 - Villejuif - France | Contact (sur clinicalTrials) | ||||
| Exelixis Clinical Site #118 - 63011 - Clermont-Ferrand - France | Contact (sur clinicalTrials) | ||||
| Exelixis Clinical Site #63 - 44805 - Saint-Herblain - France | Contact (sur clinicalTrials) | ||||
| Exelixis Clinical Site #64 - 06189 - Nice - France | Contact (sur clinicalTrials) | ||||
| Exelixis Clinical Site #75 - 67200 - Strasbourg - France | Contact (sur clinicalTrials) | ||||
| Exelixis Clinical Site #79 - 14076 - Caen - France | Contact (sur clinicalTrials) | ||||
| Exelixis Clinical Site #80 - 35042 - Rennes - France | Contact (sur clinicalTrials) | ||||
| Exelixis Clinical Site #83 - 75010 - Paris - France | Contact (sur clinicalTrials) | ||||
| Exelixis Clinical Site #84 - 54519 - Vandœuvre-lès-Nancy - France | Contact (sur clinicalTrials) | ||||
| Exelixis Clinical Site #85 - 25030 - Besançon - France | Contact (sur clinicalTrials) | ||||
| Exelixis Clinical Site #91 - 75015 - Paris - France | Contact (sur clinicalTrials) | ||||
| Exelixis Clinical Site #92 - 13273 - Marseille - France | Contact (sur clinicalTrials) | ||||
| Exelixis Clinical Site #96 - 33000 - Bordeaux - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
Inclusion Criteria:
- Cytologically or histologically confirmed solid tumor that is unresectable, locally
advanced or metastatic.
- Dose-Escalation Cohorts: Subjects 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): Subjects with unresectable advanced or metastatic RCC
with a clear cell component who have not received prior systemic therapy.
- Note: Prior non-VEGF targeted adjuvant or neoadjuvant is allowed if disease
recurrence occurred 6 months after the last dose.
- Expansion Cohort 2 (ccRCC): Subjects with unresectable advanced or metastatic RCC
with a clear cell component.
- Must have radiographically progressed after a combination therapy consisting of
a PD-1/PD-L1 targeting mAb with a 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): Subjects 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 subjects 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 (UC, ICI-experienced): Subjects 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 PD-1/PD-L1 targeting ICI therapy
given as monotherapy, combination therapy, maintenance therapy or adjuvant
therapy.
- Must have received no more than 2 prior lines of systemic anticancer therapy
for unresectable advanced or metastatic disease.
- Expansion Cohort 6 (nccRCC): Subjects with unresectable advanced or metastatic
nccRCC of the following subtypes: Papillary, unclassified RCC, and
translocation-associated, FH deficient and 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): Subjects with locally advanced, or metastatic and/or
unresectable HCC that is not amenable to curative treatment or locoregional therapy.
- Expansion Cohort 8 (NSCLC): Subjects 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): Subjects 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): Subjects with histologically confirmed unresectable,
locally advanced, or metastatic adenocarcinoma of the colon or rectum.
- Expansion Cohort 11 (HNSCC): Subject 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): Subjects with unresectable advance or metastatic RCC
with a clear cell component, including subjects 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 (ccRCC): Subjects with unresectable advanced or metastatic RCC
with a clear component, including subjects 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 subjects and their partners must agree to use highly
effective methods of contraception.
- Female subjects of childbearing potential must not be pregnant at screening.
- Cytologically or histologically confirmed solid tumor that is unresectable, locally
advanced or metastatic.
- Dose-Escalation Cohorts: Subjects 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): Subjects with unresectable advanced or metastatic RCC
with a clear cell component who have not received prior systemic therapy.
- Note: Prior non-VEGF targeted adjuvant or neoadjuvant is allowed if disease
recurrence occurred 6 months after the last dose.
- Expansion Cohort 2 (ccRCC): Subjects with unresectable advanced or metastatic RCC
with a clear cell component.
- Must have radiographically progressed after a combination therapy consisting of
a PD-1/PD-L1 targeting mAb with a 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): Subjects 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 subjects 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 (UC, ICI-experienced): Subjects 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 PD-1/PD-L1 targeting ICI therapy
given as monotherapy, combination therapy, maintenance therapy or adjuvant
therapy.
- Must have received no more than 2 prior lines of systemic anticancer therapy
for unresectable advanced or metastatic disease.
- Expansion Cohort 6 (nccRCC): Subjects with unresectable advanced or metastatic
nccRCC of the following subtypes: Papillary, unclassified RCC, and
translocation-associated, FH deficient and 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): Subjects with locally advanced, or metastatic and/or
unresectable HCC that is not amenable to curative treatment or locoregional therapy.
- Expansion Cohort 8 (NSCLC): Subjects 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): Subjects 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): Subjects with histologically confirmed unresectable,
locally advanced, or metastatic adenocarcinoma of the colon or rectum.
- Expansion Cohort 11 (HNSCC): Subject 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): Subjects with unresectable advance or metastatic RCC
with a clear cell component, including subjects 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 (ccRCC): Subjects with unresectable advanced or metastatic RCC
with a clear component, including subjects 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 subjects and their partners must agree to use highly
effective methods of contraception.
- Female subjects of childbearing potential must not be pregnant at screening.
- For all Dose-Escalation cohorts: Prior treatment with XL092. For all Expansion
Cohorts: Prior treatment with XL092, nivolumab, ipilimumab or relatlimab with the
following exceptions: Prior PD-1/PD-L1, LAG-3 and 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 (ccRCC).
- 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.
- Subjects 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): Subjects who have had recurrence within the 6 months
of completing adjuvant anti-PD-(L)1 treatment.
- For Cohort 6 (nccRCC, 1L): Subjects 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.
- Subjects who have received any local anticancer therapy including surgery, PEI,
RFA, MWA, transarterial chemoembolization (TACE), or transarterial
radioembolization (TARE) within 28 days prior to first dose.
- Subjects 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, MSS, 2L+), and 11 (HNSCC):
- Troponin T (TnT) or I (TnI) > 2 × institutional ULN.
Note: Additional Inclusion and Exclusion criteria may apply.