POD1UM-204: Safety and Efficacy of Retifanlimab (INCMGA00012) Alone or in Combination With Other Therapies in Participants With Advanced or Metastatic Endometrial Cancer Who Have Progressed on or After Platinum-based Chemotherapy.
Study Details
Study Description
Brief Summary
This is a multicenter, open-label, nonrandomized, Phase 2 umbrella study of retifanlimab in participants who have advanced or metastatic endometrial cancer that has progressed on or after platinum-based chemotherapy. retifanlimab will be administered as monotherapy or in combination with other immunotherapy or targeted agents.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Group A - retifanlimab Select participants naïve to checkpoint inhibitors will be administered retifanlimab intravenously |
Drug: retifanlimab
INCMGA00012 administered intravenously on Day 1 of each 28-day cycle for up to 26 cycles.
Other Names:
|
Experimental: Group B - retifanlimab Select participants naïve to checkpoint inhibitors will be administered retifanlimab intravenously |
Drug: retifanlimab
INCMGA00012 administered intravenously on Day 1 of each 28-day cycle for up to 26 cycles.
Other Names:
|
Experimental: Group C - retifanlimab + epacadostat Select participants who are allowed on prior checkpoint inhibitors will be administered retifanlimab intravenously in combination with oral epacadostat (IDO1 inhibitor) |
Drug: retifanlimab
INCMGA00012 administered intravenously on Day 1 of each 28-day cycle for up to 26 cycles.
Other Names:
Drug: epacadostat
epacadostat will be administered orally BID.
|
Experimental: Group D - retifanlimab + pemigatinib Select participants who are allowed on prior checkpoint inhibitors will be administered retifanlimab intravenously in combination with oral pemigatininb (FGFR 1,2,3 inhibitor) |
Drug: retifanlimab
INCMGA00012 administered intravenously on Day 1 of each 28-day cycle for up to 26 cycles.
Other Names:
Drug: pemigatinib
pemigatinib will be administered orally QD.
|
Experimental: Group E - retifanlimab + epacadostat Select participants naïve to checkpoint inhibitors will be administered retifanlimab intravenously in combination with oral epacadostat |
Drug: retifanlimab
INCMGA00012 administered intravenously on Day 1 of each 28-day cycle for up to 26 cycles.
Other Names:
Drug: epacadostat
epacadostat will be administered orally BID.
|
Experimental: Group F - retifanlimab + INCAGN02385 and INCAGN02390 Select participants who are allowed on prior checkpoint inhibitors will be administered retifanlimab in combination with INCAGN02385 and INCAGN02390 intravenously |
Drug: INCAGN02385
INCAGN2385 will be administered every 2 weeks
Drug: INCAGN02390
INCAGN2390 will be administered every 2 weeks
|
Outcome Measures
Primary Outcome Measures
- Group A - Objective Response Rate [up to 2.5 years]
Defined as the proportion of participants having a CR or PR according to RECIST v1.1, as assessed by Independent Central Review committee
Secondary Outcome Measures
- Group A -Duration of Response [up to 2.5 years]
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.
- Group A - Disease Control Rate [up to 2.5 years]
Defined as the proportion of participants with CR, PR, or SD (as determined by ICR) as best response.
- Group A - Overall Survival [up to 3.5 years]
Defined as the time from the first dose of study treatment until death due to any cause.
- Group A - Progression Free Survival [up to 3.5 years]
Defined as the time from the first dose of study treatment until disease progression (as determined by ICR) or death due to any cause.
- Group B -Duration of Response [up to 2.5 years]
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.
- Group B - Disease Control Rate [up to 2.5 years]
Defined as the proportion of participants with CR, PR, or SD (as determined by ICR) as best response.
- Group B - Overall Survival [up to 3.5 years]
Defined as the time from the first dose of study treatment until death due to any cause.
- Groups B - Objective Response Rate [up to 2 years]
Defined as the proportion of participants having a CR or PR according to RECIST v1.1, as assessed by Independent Central Review committee
- Group B - Progression Free Survival [up to 3.5 years]
Defined as the time from the first dose of study treatment until disease progression (as determined by ICR) or death due to any cause.
- Groups C, D, E and F - Objective Response Rate [up to 2 years]
Defined as the proportion of participants having a CR or PR according to RECIST v1.1, as assessed by Independent Central Review committee
- Number of Treatment-Related Adverse Events [up to 4 years]
Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Ability to comprehend and willingness to sign a written ICF for the study. Note for Germany: This excludes individuals who are housed in an institution due to official or court order Women 18 years of age or older (or as applicable per local country requirements).
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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.
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Groups A, B, and E: Have not been previously treated with a PD-(L)1 inhibitor.
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Group A only: Tumor tissue tested as MSI-High
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Group B only: Tumor tissue tested as deficient MMR or an ultra-mutated POLE tumor.
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Group D only: Tumor tissue tested as having an FGFR 1,2,3 mutation or alteration characterized as per protocol.
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Group E: Tumor tissue tested as MSS and PD-L1 positive.
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Group F: Radiological evidence of disease progression on or after prior PD (L)1 therapy and Tumor tissue tested as MSI-H
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Must have at least 1 measurable tumor lesion per RECIST v1.1.
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Willing to provide tumor tissue sample (fresh or archived).
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ECOG performance status 0 to 1.
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Willingness to avoid pregnancy.
Exclusion Criteria:
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Group A, B and E only: Histologically confirmed diagnosis of carcinosarcoma of the uterus.
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Histologically confirmed diagnosis of sarcoma of the uterus.
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Has disease eligible for potentially curative treatment.
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Receipt of anticancer therapy within 28 days of the first administration of study treatment, with the exception of localized radiotherapy.
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Toxicity of prior therapy that has not recovered to ≤ Grade 1 or baseline unless approved by the medical monitor.
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Groups C, D and F (combinations): limiting immune-related toxicity during prior checkpoint inhibitor therapy.
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Group F only: Previous treatment with LAG-# or TIM-3 therapy or lenvatinib; multiple metastases that achieved mixed tumor response to prior anti-PD-(L)1 therapy
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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.
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Receiving chronic systemic steroids (> 10 mg/day of prednisone or equivalent):
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Known active CNS metastases and/or carcinomatous meningitis.
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Has known active hepatitis B or C.
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Has received a live vaccine within 28 days of the planned start of study treatment.
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Evidence of interstitial lung disease or active, noninfectious pneumonitis.
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Participants who are known to be HIV-positive with some protocol exceptions.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Alaska Womens Cancer Care Akwcc | Anchorage | Alaska | United States | 99508 |
2 | Honorhealth | Phoenix | Arizona | United States | 85016 |
3 | Arizona Oncology Associates | Tucson | Arizona | United States | 85711 |
4 | UCLA Medical Hematology & Oncology | Los Angeles | California | United States | 90048 |
5 | Broward Health Medical Center | Fort Lauderdale | Florida | United States | 33316 |
6 | Mount Sinai Medical Center Comprehensive Cancer Center | Miami Beach | Florida | United States | 33140 |
7 | Miami Cancer Institute | Miami | Florida | United States | 33176 |
8 | Advent Health Medical Group-Orlando 2501 | Orlando | Florida | United States | 32804 |
9 | H. Lee Moffitt Cancer Center and Research Institute Hospital | Tampa | Florida | United States | 33612-9497 |
10 | Georgia Cancer Center | Augusta | Georgia | United States | 30912 |
11 | Barbara Ann Karmanos Cancer Hospital | Detroit | Michigan | United States | 48201 |
12 | Minnesota Oncology - Maplewood | Minneapolis | Minnesota | United States | 55404 |
13 | Midwest Cancer Care | Kansas City | Missouri | United States | 64132 |
14 | Washington University | Saint Louis | Missouri | United States | 63110 |
15 | Billings Clinic Cancer Center | Billings | Montana | United States | 59101 |
16 | Comprehensive Cancer Centers of Nevada | Las Vegas | Nevada | United States | 89148 |
17 | New Mexico Cancer Care Alliance | Albuquerque | New Mexico | United States | 87131 |
18 | Nyu Clinical Cancer Center | New York | New York | United States | 10032 |
19 | University of North Carolina At Chapel Hill | Chapel Hill | North Carolina | United States | 27514 |
20 | The Ohio State University Wexner Medical Center Division of Gynecologic Oncology | Hilliard | Ohio | United States | 43026 |
21 | Willamette Valley Cancer Institute | Eugene | Oregon | United States | 97401-8122 |
22 | Texas Oncology - Tyler | Sioux Falls | South Dakota | United States | 57104 |
23 | Tennessee Oncology | Nashville | Tennessee | United States | 37203 |
24 | Texas Oncology-Austin Center | Austin | Texas | United States | 78731 |
25 | Texas Oncology | Fort Worth | Texas | United States | 76104-3902 |
26 | Memorial Hermann Cancer Center | Houston | Texas | United States | 77030 |
27 | Texas Oncology San Antonio | San Antonio | Texas | United States | 78240 |
28 | Texas Oncology the Woodlands | Shenandoah | Texas | United States | 77380 |
29 | Virginia Commonwealth University | Richmond | Virginia | United States | 23298 |
30 | O.L.V Ziekenhuis | Aalst | Belgium | 09300 | |
31 | Institut Jules Bordet | Brussels | Belgium | 01000 | |
32 | Ghent University Hospital | Gent | Belgium | 09000 | |
33 | Universitaire Ziekenhuis Leuven - Gasthuisberg | Leuven | Belgium | 03000 | |
34 | Centre Hospitalier Universitaire de Liege - Sart Tilman | Liege | Belgium | 04000 | |
35 | Chu Ucl Namur de Saint Elisabeth | Namur | Belgium | 05000 | |
36 | Beijing Cancer Hospital | Beijing | China | 100142 | |
37 | Xiangya Hospital Central South University | Changsha | China | 410000 | |
38 | Hunan Cancer Hospital | Changsha | China | 410013 | |
39 | West China Second University Hospital, Sichuan University | Chengdu | China | 610066 | |
40 | Chongqing University Cancer Hospital | Chongqing | China | 400030 | |
41 | Sun Yat-Sen Memorial Hospital Sun Yat-Sen University | Guangzhou | China | 510000 | |
42 | University of Science and Technology of China-First Affiliated Hospital (Anhui Provincial Hospital) | Hefei | China | 230001 | |
43 | Qilu Hospital of Shandong University | Jinan | China | 250000 | |
44 | The Affiliated Drum Tower Hospital of Nanjing University | Nanjing | China | 210000 | |
45 | Tsingdao Central Hospital | Qingdao | China | 266042 | |
46 | Obstetrics and Gynecology Hospital of Fudan University | Shanghai | China | 200011 | |
47 | The Second Hospital of Shanxi Medical University | Taiyuan | China | 30001 | |
48 | The First Affiliated Hospital of Xian Jiaotong University | Xi'an | China | 710061 | |
49 | The First Affiliated Hospital of Xiamen University | Xiamen | China | 361003 | |
50 | Henan Cancer Hostipal | Zhengzhou | China | 450003 | |
51 | Chu Besancon Hospital Jean Minjoz | Besancon | France | 25030 | |
52 | Institut Bergonie | Bordeaux Cedex | France | 33076 | |
53 | Hospital Cochin Cancerologie | Paris | France | 75006 | |
54 | Cario - Centre Armoricain de Radiotherapie Imagerie Medicale Et Oncologie | Plerin | France | 22190 | |
55 | Centre de Lutte Contre Le Cancer - Institut de Cancerologie de L'Ouest - Rene Gauducheau | Saint Herblain | France | 44800 | |
56 | High Technology Hospital Medcenter Llc | Batumi | Georgia | 06000 | |
57 | Jsc Evex Hospitals | Kutaisi | Georgia | 04600 | |
58 | Llc Todua Clinic | Tbilisi | Georgia | 00112 | |
59 | Caucasus Medical Centre Llc | Tbilisi | Georgia | 00186 | |
60 | Ltd Innova | Tbilisi | Georgia | 00186 | |
61 | Multiprofile Clinic Consilium Medulla Llc | Tbilisi | Georgia | 00186 | |
62 | Charite - Campus Virchow-Klinikum | Berlin | Germany | 13353 | |
63 | Universitatsklinikum Bonn Aoer | Bonn | Germany | 53127 | |
64 | University Clinic Carl Gustav Carus Technical University Dresden | Dresden | Germany | 01307 | |
65 | Universitarsfrauenklinik Ulm | ULM | Germany | 89075 | |
66 | Alexandra General Hospital of Athens | Athens | Greece | 11528 | |
67 | University Hospital of West Attica - Attikon | Athens | Greece | 12462 | |
68 | Hygeia Hospital | Marousi | Greece | 15123 | |
69 | Euromedica General Clinic of Thessaloniki | Thessaloniki | Greece | 54645 | |
70 | L AZIENDA OSPEDALIERO-UNIVERSITARIA DI BOLOGNA POLICLINICO S. ORSOLA � MALPIGHI | Bologna | Italy | 40138 | |
71 | Presidio Ospedaliero Di Summa Antonio Perrino | Brindisi | Italy | 72100 | |
72 | Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori | Meldola | Italy | 47014 | |
73 | Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San Raffaele | Milano | Italy | 20132 | |
74 | Fondazione Irccs Istituto Nazionale Dei Tumori | Milano | Italy | 20133 | |
75 | European Institute of Oncology | Milano | Italy | 20141 | |
76 | Istituto Nazionale Tumori Irccs Fondazione Pascale | Napoli | Italy | 80131 | |
77 | Iov - Istituto Oncologico Veneto Irccs | Padova | Italy | 35128 | |
78 | Fondazione Policlinico Universitario Agostino Gemelli Irccs | Roma | Italy | 00168 | |
79 | Ospedale Santa Maria Ca Foncello | Treviso | Italy | 31100 |
Sponsors and Collaborators
- Incyte Corporation
- GOG Foundation
- European Network of Gynaecological Oncological Trial Groups (ENGOT)
Investigators
- Study Director: Mark Cornfield, Incyte Corporation
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- INCMGA 0012-204