Carboplatin-paclitaxel With Retifanlimab or Placebo in Participants With Locally Advanced or Metastatic Squamous Cell Anal Carcinoma (POD1UM-303/InterAACT 2).

Sponsor

Incyte Corporation (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04472429

Collaborator

(none)

300

Enrollment

Locations

Arms

45.5

Anticipated Duration (Months)

3.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is a Phase 3 global, multicenter, placebo-controlled double-blind randomized study that will enroll participants with inoperable locally recurrent or metastatic SCAC not previously treated with systemic chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Squamous Cell Carcinoma of the Anal Canal	Drug: carboplatin Drug: paclitaxel Drug: retifanlimab	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Double Blind

Primary Purpose:

Treatment

Official Title:

A Phase 3 Global, Multicenter, Double-Blind Randomized Study of Carboplatin-Paclitaxel With INCMGA00012 or Placebo in Participants With Inoperable Locally Recurrent or Metastatic Squamous Cell Carcinoma of the Anal Canal Not Previously Treated With Systemic Chemotherapy (POD1UM-303/InterAACT 2)

Actual Study Start Date :

Jan 12, 2021

Anticipated Primary Completion Date :

Oct 24, 2024

Anticipated Study Completion Date :

Oct 27, 2024

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Group A : carboplatin+paclitaxel+placebo Participants will receive carboplatin on Day 1,paclitaxel on Day1,8, 15, and placebo on Day 1 of each 28 day cycle	Drug: carboplatin carboplatin will be administered intravenous on Day 1 of each 28 day cycle Drug: paclitaxel paclitaxel will be administered intravenous on Days 1,8, and 15 of each 28 day cycle
Experimental: Group B : carboplatin+paclitaxel+retifanlimab Participants will receive carboplatin on Day 1,paclitaxel on Day1,8, 15, and retifanlimab on Day 1 of each 28 day cycle	Drug: carboplatin carboplatin will be administered intravenous on Day 1 of each 28 day cycle Drug: paclitaxel paclitaxel will be administered intravenous on Days 1,8, and 15 of each 28 day cycle Drug: retifanlimab retifanlimab will be administered intravenous on Day 1 of each 28 day cycle Other Names: INCMGA00012

Arm

Intervention/Treatment

Placebo Comparator: Group A : carboplatin+paclitaxel+placebo

Participants will receive carboplatin on Day 1,paclitaxel on Day1,8, 15, and placebo on Day 1 of each 28 day cycle

Drug: carboplatin

carboplatin will be administered intravenous on Day 1 of each 28 day cycle

Drug: paclitaxel

paclitaxel will be administered intravenous on Days 1,8, and 15 of each 28 day cycle

Experimental: Group B : carboplatin+paclitaxel+retifanlimab

Participants will receive carboplatin on Day 1,paclitaxel on Day1,8, 15, and retifanlimab on Day 1 of each 28 day cycle

Drug: carboplatin

carboplatin will be administered intravenous on Day 1 of each 28 day cycle

Drug: paclitaxel

paclitaxel will be administered intravenous on Days 1,8, and 15 of each 28 day cycle

Drug: retifanlimab

retifanlimab will be administered intravenous on Day 1 of each 28 day cycle

Other Names:

INCMGA00012

Outcome Measures

Primary Outcome Measures

Progression Free Survival (PFS) [up to 4.5 years]
Defined as the time from the date of randomization until disease progression according to RECIST v1.1 by BICR or death due to any cause.

Secondary Outcome Measures

Overall Survival (OS) [Up to 4.5 years]
Defined as the time from the date of randomization until death due to any cause.
Overall Response Rate (ORR) [Up to 4.5 years]
Defined as the proportion of participants who have a confirmed complete response or partial response per RECIST v1.1 based on BICR.
Duration of Response (DOR) [Up to 4.5 years]
Defined as the time from the earliest date of documented response until earliest date of disease progression (per RECIST v1.1 based on BICR) or death from any cause, whichever comes first.
Disease Control Rate(DCR) [Up to 4.5 years]
Defined as the number of participants maintaining either an ORR or stable disease.
Number of treatment-emergent adverse events [Up to 4.5 years]
Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study treatment up to 90 days after last dose of study treatment.
Cmax of retifanlimab when administered with chemotherapy [Up to 4.5 years]
Maximum observed plasma or serum concentration.
tmax of retifanlimab when administered with chemotherapy [Up to 4.5 years]
Time to maximum concentration
Cmin of retifanlimab when administered with chemotherapy [Up to 4.5 years]
Minimum observed plasma or serum concentration over the dose interval
AUC0-t of retifanlimab when administered with chemotherapy [Up to 4.5 years]
Area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Able to comprehend and willing to sign a written ICF for the study.
Are 18 years of age or older (or as applicable per local country requirements).
Histologically or cytologically verified, inoperable locally recurrent or metastatic SCAC.
No prior systemic therapy other than the following: a. Chemotherapy administered concomitantly with radiotherapy as a radiosensitizing agent is permitted.

Prior neoadjuvant or adjuvant therapy if completed ≥ 6 months before study entry.

Has measurable disease per RECIST v1.1 as determined by local site investigator/radiology assessment. Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, are usually not considered measurable unless there has been demonstrated progression in the lesion.
Able and willing to provide adequate tissue sample and whole blood sample with central testing result prior to randomization. Biopsy for archival samples should have occurred within 9 months prior to randomization.
ECOG performance status 0 to 1.
If HIV-positive, then must be stable as defined by: a. CD4+ count ≥ 200/μL, b. Undetectable viral load per standard of care assay, c. Receiving antiretroviral therapy (ART/HAART) for at least 4 weeks prior to study enrollment, and have not experienced any HIV-related opportunistic infection for at least 4 weeks prior to study enrollment.
Willingness to avoid pregnancy or fathering children

Exclusion Criteria:

Has received prior PD-(L)1 directed therapy
Has received prior radiotherapy with or without radiosensitizing chemotherapy within 28 days of Cycle 1 Day 1 except for palliative radiation (30 Gy or less) which is restricted for 14 days of Cycle 1 Day 1 (note: all toxicities associated should have resolved to Grade ≤ 1).
Participants with laboratory outside of the protocol defined ranges.
History of second malignancy within 3 years (with exceptions).
Clinically significant pulmonary, cardiac, gastrointestinal or autoimmune disorders.
Active bacterial, fungal, or viral infections, including hepatitis A, B, and C and IV antibiotic use within 7 days of Cycle 1 Day 1.
Receipt of a live vaccine within 28 days of planned start of study therapy.
History of organ transplant, including allogeneic stem cell transplantation.
Known active CNS metastases and/or carcinomatous meningitis.
Known hypersensitivity to platinum, paclitaxel, another monoclonal antibody, or any of the excipients that cannot be controlled with standard measures (eg, antihistamines, corticosteroids).
Participant is pregnant or breastfeeding.
Current use of protocol defined prohibited medication.
Has pre-existing peripheral neuropathy that is ≥ Grade 2 by CTCAE v5.
Inability or unlikely, in the opinion of the investigator, to comply with the Protocol requirements

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Arizona Cancer Center	Tucson	Arizona	United States	85724
2	City of Hope National Medical Center	Duarte	California	United States	91010
3	UC Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
4	Sansum Clinic	Santa Barbara	California	United States	93105
5	Rocky Mountain Cancer Center	Denver	Colorado	United States	80218
6	Sylvester Comprehensive Cancer Center	Miami	Florida	United States	33136
7	Ochsner Clinic	New Orleans	Louisiana	United States	70121
8	Maryland Oncology Hematology, P.A.	Columbia	Maryland	United States	21044
9	Mayo Clinic	Rochester	Minnesota	United States	55905
10	Texas Oncology	Austin	Texas	United States	78745
11	Baylor Scott and White Research Institute	Dallas	Texas	United States	75246
12	Renovatio Clinical Consultants Llc	The Woodlands	Texas	United States	77380
13	Texas Oncology - Wichita Falls Texoma Cancer Center	Wichita Falls	Texas	United States	76310
14	Virginia Cancer Specialists, Pc	Arlington	Virginia	United States	22205
15	Blue Ridge Cancer Care	Roanoke	Virginia	United States	24014
16	Princess Alexandra Hospital Australia	Woolloongabba	Queensland	Australia	04102
17	Flinders Medical Centre	Bedford Park	South Australia	Australia	5042
18	Monash Medical Centre Clayton	Clayton	Victoria	Australia	03168
19	Zna Middelheim	Antwerpen		Belgium	02020
20	Ulb Hospital Erasme	Bruxelles		Belgium	01070
21	Aarhus University Hospital	Aarhus		Denmark	8200
22	Herlev Og Gentofte Hospital	Herlev		Denmark	02730
23	Vejle Hospital	Vejle		Denmark	07100
24	Institut de Cancerologie de L Ouest - Site Paul Papin	Angers Cedex 2		France	49055
25	Chu Besancon Hospital Jean Minjoz	Besancon		France	25030
26	Centre Hospitalier Universitaire de Bordeaux	Bordeaux Cedex		France	33075
27	Centre Leon Berard	Lyon		France	69008
28	Chu Hopital de La Timone	Marseille Cedex 5		France	13385
29	Institut Du Cancer de Montpellier	Montpellier		France	34298
30	Centre Antoine Lacassagne	Nice		France	06189
31	Hospital Universitaire Pitie-Salpetriere	Paris Cedex 13		France	75651
32	Hospital de La Miletrie	Poitiers Cedex		France	86021
33	Chu de Rennes - Hospital Pontchaillou	Rennes Cedex 09		France	35033
34	Hopital Charles Nicolle Chu Rouen Hospital de Bois-Guillaume	Rouen Cedex		France	76031
35	Centre de Lutte Contre Le Cancer - Institut de Cancerologie de L'Ouest - Rene Gauducheau	Saint Herblain		France	44800
36	Strasbourg Oncologie Liberale	Strasbourg Cedex		France	67000
37	Chu Toulouse Hopital Rangueil	Toulouse Cedex 9		France	31059
38	Institut Gustave Roussy	Villejuif Cedex		France	94805
39	Universitatsklinikum Bonn Aoer	Bonn		Germany	53127
40	University Clinic Carl Gustav Carus Technical University Dresden	Dresden		Germany	01307
41	University Medical Centre Hamburg-Eppendorf Centre of Oncology	Hamburg		Germany	20246
42	Asklepios Klinik Altona	Hamburg		Germany	22763
43	Fondazione Irccs Istituto Nazionale Dei Tumori	Milano		Italy	20133
44	European Institute of Oncology	Milano		Italy	20141
45	Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda	Milano		Italy	20162
46	Fondazione Irccs Ca Granda Ospedale Maggiore	Milan		Italy	20122
47	Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda	Milan		Italy	20162
48	University Di Cagliari-Presidio Policlinico Monserrato	Monserrato		Italy	09042
49	Azienda Ospedaliera Universitaria University Degli Studi Della Campania Luigi Vanvitelli	Napoli		Italy	80131
50	Iov - Istituto Oncologico Veneto Irccs	Padova		Italy	35128
51	Azienda Ospedaliero Universitaria Pisana	Pisa		Italy	56126
52	Ospedale Degli Infermi	Rimini		Italy	47923
53	I.R.C.C.S. Casa Sollievo Della Sofferenza	San Giovanni Rotondo		Italy	71013
54	Azienda Ospedaliero Universitaria Ospedali Riuniti	Torrette		Italy	60020
55	National Cancer Center Hospital	Chuo-ku		Japan	104-0045
56	Kyushu University Hospital	Fukuoka-shi		Japan	812-8582
57	Saitama Medical University International Medical Center	Hidaka-shi		Japan	350-1298
58	Aichi Cancer Center Hospital	Nagoya-shi		Japan	464-8681
59	Osaka International Cancer Institute	Osaka-shi		Japan	541-8567
60	Tohoku University Hospital	Sendai-shi		Japan	980-8574
61	Center Hospital of the National Center For Global Health and Medicine	Shinjuku-ku		Japan	162-8655
62	Haukeland University Hospital	Bergen		Norway	05021
63	Oslo Universitetssykehus	Oslo		Norway	00450
64	Panoncology Trials Pan American Center For Oncology Trials, Llc	San Juan		Puerto Rico	00935
65	Complejo Hospitalario Universitario A Coruna	A Coruna		Spain	15006
66	Hospital General Universitario Vall D Hebron	Barcelona		Spain	08035
67	Hospital Clinic de Barcelona	Barcelona		Spain	08036
68	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
69	Hospital Universitario de La Paz	Madrid		Spain	28046
70	Son Espases University Hospital	Palma de Mallorca		Spain	07120
71	Hospital Universitario Virgen Del Rocio	Sevilla		Spain	41013
72	Hospital Universitario Miguel Servet	Zaragoza		Spain	50009
73	Sahlgrenska University Hospital	Goteborg		Sweden	413 45
74	Skaenes Universitetssjukhus Lund	Lund		Sweden	22185
75	Stockholm South General Hospital Sodersjukhuset	Stockholm		Sweden	118 83
76	Royal Sussex County Hospital	Brighton		United Kingdom	BN2 5BE
77	Royal Surrey County Hospital	Guildford		United Kingdom	GU2 7XX
78	Castle Hill Hospital	Hull		United Kingdom	HU16 5JQ
79	Leeds Teaching Hospital	Leeds		United Kingdom	LS 9 7TF
80	Royal Free London Nhs Foundation Trust	London		United Kingdom	NW3 2QG
81	The Royal Marsden Nhs Foundation Trust - Chelsea	London		United Kingdom	SW3 6JJ
82	The Christie Nhs Foundation Trust Uk	Manchester		United Kingdom	M20 4BV
83	Churchill Hospital	Oxford		United Kingdom	OX3 7LE
84	Royal Preston Hospital	Preston		United Kingdom	PR2 9HT
85	The Royal Marsden Nhs Foundation Trust - Sutton	Sutton		United Kingdom	SM2 5PT
86	Royal Cornwall Hospital Truro Sunrise Centre	Truro		United Kingdom	TR1 3LQ