Endometrial cancer MedDRA version: 21.0 Level: PT Classification code 10014733 Term: Endometrial cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10014734 Term: Endometrial cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Incyte Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Ability to comprehend and willingness to sign a written ICF for the study. 2. Women 18 years of age or older (or as applicable per local country requirements). 3. Histologically confirmed diagnosis of advanced or metastatic endometrial cancer with disease progression on or after treatment with at least 1 platinum-containing regimen for advanced or metastatic disease. Note: for Group E only: No more than 1 systemic regimen for advanced or metastatic disease is allowed. For all groups neoadjuvant chemotherapy in an early disease stage is allowable. Prior hormonal therapy is allowable in any disease setting. 4. Groups A, B and E: Have not been previously treated with a PD-(L)1 inhibitor. 5.Group F only: Radiological evidence of disease progression on or after prior PD (L)1 therapy. Participant must have received at least 2 doses of prior PD-(L)1 therapy. Participant may have received PD-(L)1 therapy either alone or in combination. Disease progression must have occurred on or after the first ontreatment scan and must have been confirmed subsequently by imaging = 4 weeks after evidence of initial disease progression. Note: baseline scan within the study may serve as a confirmatory scan for progressive disease. Participant may have achieved objective response (CR or PR) to prior PD-(L)1 therapy followed by disease recurrence. 6. Group A only: Tumor tissue centrally tested as MSI-H using Promega OncoMate™ MSI Dx assay. See Section 8.1.2.1 for assay details. 7. Group B only: Tumor tissue centrally tested as dMMR using MMR IHC assay or known to have ultra-mutated POLE tumor per locally available result. See Section 8.1.2.1 for assay details. Note: POLE ultra-mutated participants need to have documented POLE exonuclease domain mutation (residues 268-471) known to have damaging effect on exonuclease domain function. Test type (eg, PCR or NGS) should be documented in the EDC. 8. Group D only: Tumor tissue tested locally or centrally, based on CLIAcertified (or similar certification) laboratory assays, as having FGFR1-3 fusions or rearrangements characterized as follows: a. FGFR1-3 in-frame fusions, b. any FGFR2 rearrangement, or c. FGFR1-3 rearrangement with known partner. Note: See Appendix C for most detailed information on FGFR fusions and/or rearrangements allowed. 9. Group E only:Tumor tissue centrally tested as PD-L1–positive using Ventana SP263 assay (determined based on PD-L1 staining of TCs, ICs, and ICPs and tested as MSS locally or centrally using PCR assay. Microsatellite stability results obtained locally would need to be subsequently confirmed centrally after participant's enrollment. 10.Group F only: Tumor tissue tested as MSI-H centrally or locally using PCR assay. MSI H results obtained locally would need to be subsequently confirmed centrally after participant's enrollment. 11. Must have at least 1 measurable tumor lesion per RECIST v1.1. Note: Lesions to be used as measurable disease for the purpose of response assessment must either a) not reside in a field that has been subjected to prior radiotherapy, or b) have demonstrated clear evidence of radiographic progression since the completion of prior radiotherapy and prior to study enrollment. 12. Willing to provide tumor tissue sample (fresh or archived). 13. ECOG performance status 0 to 1. 14. Willingness to avoid pregnancy based on the criteria below. a. Women of childbearing potential must have a negative serum pregnancy test at screening and must agree to take appropriate
Exclusion criteria
Exclusion criteria: 1. Groups A,B and E only: Histologically confirmed diagnosis of carcinosarcoma of the uterus. 2. Histologically confirmed diagnosis of sarcoma of the uterus. 3. Has disease eligible for potentially curative treatment with standard chemotherapy, surgical resection, or chemoradiotherapy. 4. Receipt of anticancer therapy within 28 days of the first administration of study treatment, with the exception of localized radiotherapy. 5. Toxicity of prior therapy that has not recovered to = Grade 1 (with the exception of alopecia and anemia not requiring transfusional support), unless approved by the medical monitor. 6. Groups C ,D and F (combinations): Immune-related toxicity during prior checkpoint inhibitor therapy for which permanent discontinuation of therapy is recommended (per product label or consensus guidelines), OR severe immune-related toxicity requiring intensive (eg, use of infliximab) or prolonged immunosuppression (eg, > 6 weeks) to manage (with the exception of endocrinopathy that is well-controlled on replacement hormones). 7.Group F only: Previous treatment with LAG-3 or TIM-3 directed therapy or lenvatinib. 8.Group F only: Participants with multiple metastases that achieved mixed tumor response to prior anti–PD-(L)1 therapy (such as isolated progressive lesion in a context of PR/CR or SD for other lesions) or achieved overall disease progression based only on a single new lesion. 9. Participant with laboratory values at screening defined in Table 8. 10. Has an active autoimmune disease requiring systemic immunosuppression with corticosteroids (> 10 mg/day of prednisone or equivalent) or immunosuppressive drugs within 14 days before the first dose of study treatment. 11. Receiving chronic systemic corticosteroids(> 10 mg/day of prednisone or equivalent). 12. Active infections requiring systemic antibiotics or antifungal or antiviral treatment (except where warranted as per Exclusion Criteria 17 and 26) within 7 days before first dose of study treatment. 13. History of organ transplant, including allogeneic stem cell transplantation. 14. Receiving probiotics as of the first dose of study treatment. 15. Known active CNS metastases and/or carcinomatous meningitis. 16. Known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry with the exception of cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy, or cancers from which the participant has been disease-free for > 1 year, after treatment with curative intent. 17. Has known active hepatitis B or C (defined as follows) or HIV, HBV, HCV, or HDV coinfection. 18. Known hypersensitivity to any of the study drugs, excipients, or another monoclonal antibody that cannot be controlled with standard measures (eg, antihistamines and corticosteroids). 19. Participants with impaired cardiac function or clinically significant cardiac disease. 20. Women who are pregnant or breast-feeding. 21. If participant received major surgery, then they must have recovered adequately from toxicities and/or complications from the intervention before starting study treatment. 22. Has received a live vaccine within 28 days of the planned start of study treatment. 23. Evidence of interstitial lung disease or active, noninfectious pneumonitis. 24. Current use of prohibited medication as noted in Section 6.8.3. 25. Any conditio
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate antitumor activity of INCMGA00012 in Group A.;Secondary Objective: - To further evaluate clinical efficacy of INCMGA00012 monotherapy and evaluate clinical activity in the combinations. - To evaluate the safety and tolerability of INCMGA00012 as monotherapy and in combination.;Primary end point(s): Group A (INCMGA00012 monotherapy): ORR, defined as the proportion of participants having a CR or PR according to RECIST v1.1, will be determined by ICR.;Timepoint(s) of evaluation of this end point: Through end of study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Group A (INCMGA00012 monotherapy): • DOR, defined as the time from the first documented objective response (CR or PR) according to RECIST v1.1 (as determined by ICR) until disease progression or death due to any cause. • DCR, defined as the proportion of participants with CR, PR, or SD (as determined by ICR) as best response. • PFS, defined as the time from the first dose of study treatment until disease progression (as determined by ICR) or death due to any cause. • OS, defined as the time from the first dose of study treatment until death due to any cause. All other groups: • ORR, defined as the proportion of participants having a CR or PR according to RECIST v1.1 (as determined by the investigator). Safety and tolerability will be assessed by monitoring the frequency and severity of AEs and SAEs as well as laboratory test results.;Timepoint(s) of evaluation of this end point: Through end of study | — |
Countries
Belgium, China, France, Georgia, Germany, Greece, Italy, United States
Contacts
Public ContactClinical Trial Information
Incyte Corporation
Outcome results
None listed