An Umbrella Study of INCMGA00012 Alone and in Combination With Other Therapies in Participants With Advanced or Metastatic Endometrial Cancer Who Have Progressed on or After Platinum-Based Chemotherapy (POD1UM-204)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Incyte Corp.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

16 Mar 2021 → ongoing

Decision date (initial)

2023-11-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Incyte Corporation

External identifiers

EU CT number

2022-502600-79-00

EudraCT number

2020-000496-20

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacodynamic, Pharmacogenetic, Pharmacokinetic, Others

To evaluate antitumor activity of INCMGA00012 in Group A

Secondary objectives 2

1. To further evaluate clinical efficacy of INCMGA00012 monotherapy and evaluate clinical activity in the combinations.
2. To evaluate the safety and tolerability of INCMGA00012 as monotherapy and in combination.

Conditions and MedDRA coding

Endometrial cancer

Study design 5 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Ability to comprehend and willingness to sign a written ICF for the study
2. 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.
3. 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.
4. Women 18 years of age or older (or as applicable per local country requirements).
5. 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.
6. Groups A, B and E: Have not been previously treated with a PD-(L)1 inhibitor.
7. 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 on treatment 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.
8. 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.
9. 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.
10. Group D only: Tumor tissue tested locally or centrally, based on CLIA certified (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.
11. 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 enrolment.
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 precautions to avoid pregnancy (with at least 99% certainty) from screening through 6 months after the last dose of study treatment and must refrain from donating oocytes during this period. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participants and their understanding confirmed (See Appendix A). b. Women of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy

Exclusion criteria 30

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 (withthe 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 condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study treatment and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
26. Participants who are known to be HIV-positive.
27. For Group C ,D and E : History or presence of an abnormal ECG that in the investigator's opinion, is clinically meaningful. Average QTc interval > 480 milliseconds is excluded (corrected by Fridericia or Bazett formula).
28. History of a gastrointestinal condition (eg, inflammatory bowel disease, Crohn's disease, ulcerative colitis) that may affect oral drug absorption.
29. Exclusion criteria specific to a group receiving combination therapy. a. Participants enrolled in the epacadostat combination (Groups C and E only) b. Participants enrolled in the pemigatinib combination (Group D only)
30. The following participants are excluded in France: vulnerable populations according to article L.1121-6 of the French Public Health Code and adults under legal protection, or who are unable to express their consent per article L.1121-8 of the French Public Health Code, not affiliated to a social security per article L.1121-8-1 of the French Public Health Code.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 5

1. Group A and B (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
2. Group A and B (INCMGA00012 monotherapy): DCR, defined as the proportion of participants with CR, PR, or SD (as determined by ICR) as best response.
3. Group A and B (INCMGA00012 monotherapy): 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.
4. Group A and B (INCMGA00012 monotherapy): OS, defined as the time from the first dose of study treatment until death due to any cause.
5. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Incyte Corp.

Sponsor organisation

Incyte Corp.

Address

1801 Augustine Cut Off

City

Wilmington

Postcode

19803-4404

Country

United States

Scientific contact point

Organisation

Incyte Corp.

Contact name

Clinical Trial Information

Public contact point

Organisation

Incyte Corp.

Contact name

Clinical Trial Information

Third parties 9

Locations

4 EU/EEA countries · 24 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 59 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications