Clinical trial NCT04472429: Carboplatin-paclitaxel With Retifanlimab or Placebo in Participants With Locally Advanced or Metastatic Squamous Cell Anal Carcinoma (POD1UM-303/InterAACT 2).
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Squamous Cell Carcinoma of the Anal Canal
Keywords: Squamous cell carcinoma
carboplatin
paclitaxel
PD-1 Inhibitor
Anal Cancer
SCAC
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2020-07-15
Enrollment: 308
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

    b. 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

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: up to 33.9 months
Secondary outcomes:
measure: Overall Survival
timeFrame: up to 40.4 months
measure: Objective Response Rate (ORR)
timeFrame: up to 445 days
measure: Duration of Response (DOR)
timeFrame: up to 32.1 months
measure: Disease Control Rate (DCR)
timeFrame: up to 445 days
measure: Number of Participants With Any Treatment-emergent Adverse Event (TEAE ) During the Randomized Period
timeFrame: up to 535 days
measure: Number of Participants With Any TEAE Leading to Discontinuation of Study Drug During the Randomized Period
timeFrame: up to 535 days
measure: Number of Participants With Any TEAE During the Open-label Monotherapy Period
timeFrame: up 457 days
measure: Number of Participants With Any TEAE Leading to Discontinuation of Study Drug During the Open-label Monotherapy Period
timeFrame: up 457 days
measure: Cmax of Retifanlimab at Steady State When Administered With Carboplatin-paclitaxel
timeFrame: preinfusion on Day 1 of Cycles 1, 2, 4, 6, 8, and 12; immediately after infusion on Day 1 of Cycles 1 and 4
measure: Cmin of Retifanlimab at Steady State When Administered With Carboplatin-paclitaxel
timeFrame: preinfusion on Day 1 of Cycles 1, 2, 4, 6, 8, and 12; immediately after infusion on Day 1 of Cycles 1 and 4
measure: Tmax of Retifanlimab at Steady State When Administered With Carboplatin-paclitaxel
timeFrame: preinfusion on Day 1 of Cycles 1, 2, 4, 6, 8, and 12; immediately after infusion on Day 1 of Cycles 1 and 4
measure: AUC of Retifanlimab at Steady State When Administered With Carboplatin-paclitaxel
timeFrame: preinfusion on Day 1 of Cycles 1, 2, 4, 6, 8, and 12; immediately after infusion on Day 1 of Cycles 1 and 4
Other outcomes:
Locations:
city: Tucson
country: United States
facility: The University of Arizona Cancer Center
state: Arizona
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Sacramento
country: United States
facility: UC Davis Comprehensive Cancer Center
state: California
city: Santa Barbara
country: United States
facility: Sansum Clinic
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: New Orleans
country: United States
facility: Ochsner Clinic
state: Louisiana
city: Columbia
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Austin
country: United States
facility: Texas Oncology
state: Texas
city: Dallas
country: United States
facility: Baylor Scott and White Research Institute
state: Texas
city: The Woodlands
country: United States
facility: Renovatio Clinical Consultants Llc
state: Texas
city: Wichita Falls
country: United States
facility: Texas Oncology-Wichita Falls Texoma Cancer Center
state: Texas
city: Arlington
country: United States
facility: Virginia Cancer Specialists, Pc
state: Virginia
city: Roanoke
country: United States
facility: Blue Ridge Cancer Care
state: Virginia
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital Australia
state: Queensland
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Clayton
country: Australia
facility: Monash Medical Centre Clayton
state: Victoria
city: Antwerpen
country: Belgium
facility: Zna Middelheim
city: Bruxelles
country: Belgium
facility: Ulb Hospital Erasme
city: Herlev
country: Denmark
facility: Herlev Og Gentofte Hospital
city: Vejle
country: Denmark
facility: Vejle Hospital
city: Angers Cedex 2
country: France
facility: Institut de Cancerologie de L Ouest - Site Paul Papin
city: Besançon
country: France
facility: Chu Besancon Hospital Jean Minjoz
city: Bordeaux Cedex
country: France
facility: Centre Hospitalier Universitaire de Bordeaux
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille Cedex 5
country: France
facility: Chu Hopital de La Timone
city: Montpellier
country: France
facility: Institut Du Cancer de Montpellier
city: Nice
country: France
facility: Centre Antoine Laccassagne
city: Paris Cedex 13
country: France
facility: Hospital Universitaire Pitie-Salpetriere
city: Poitiers Cedex
country: France
facility: Hospital de La Miletrie
city: Rennes Cedex 09
country: France
facility: Chu de Rennes - Hospital Pontchaillou
city: Rouen Cedex
country: France
facility: Hopital Charles Nicolle Chu Rouen Hospital de Bois-Guillaume
city: Saint Herblain
country: France
facility: Centre de Lutte Contre Le Cancer - Institut de Cancerologie de L'Ouest - Rene Gauducheau
city: Strasbourg
country: France
facility: Institut de Cancerologie de Strasbourg
city: Toulouse Cedex 9
country: France
facility: Chu Toulouse Hopital Rangueil
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy
city: Bonn
country: Germany
facility: Universitatsklinikum Bonn Aoer
city: Dresden
country: Germany
facility: University Clinic Carl Gustav Carus Technical University Dresden
city: Hamburg
country: Germany
facility: Asklepios Klinik Altona
city: Milano
country: Italy
facility: Comitato Etico Fondazione Irccs Istituto Nazionale Dei Tumori Milano
city: Milano
country: Italy
facility: European Institute of Oncology
city: Milano
country: Italy
facility: Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
city: Milan
country: Italy
facility: Fondazione Irccs Ca Granda Ospedale Maggiore
city: Milan
country: Italy
facility: Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
city: Monserrato
country: Italy
facility: University Di Cagliari-Presidio Policlinico Monserrato
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria University Degli Studi Della Campania Luigi Vanvitelli
city: Padova
country: Italy
facility: Iov - Istituto Oncologico Veneto Irccs
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Rimini
country: Italy
facility: Ospedale Degli Infermi
city: San Giovanni Rotondo
country: Italy
facility: I.R.C.C.S. Casa Sollievo Della Sofferenza
city: Torrette
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedali Riuniti
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
city: Fukuoka-shi
country: Japan
facility: Kyushu University Hospital
city: Hidaka-shi
country: Japan
facility: Saitama Medical University International Medical Center
city: Nagoya-shi
country: Japan
facility: Aichi Cancer Center Hospital
city: Osaka-shi
country: Japan
facility: Osaka International Cancer Institute
city: Sendai-shi
country: Japan
facility: Tohoku University Hospital
city: Shinjuku-ku
country: Japan
facility: Center Hospital of the National Center For Global Health and Medicine
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Oslo
country: Norway
facility: Oslo Universitetssykehus
city: San Juan
country: Puerto Rico
facility: Panoncology Trials Pan American Center For Oncology Trials, Llc
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruna
city: Barcelona
country: Spain
facility: Hospital General Universitario Vall D Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario de La Paz
city: Palma de Mallorca
country: Spain
facility: Son Espases University Hospital
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Goteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: Lund
country: Sweden
facility: Skaenes Universitetssjukhus Lund
city: Stockholm
country: Sweden
facility: Stockholm South General Hospital Sodersjukhuset
city: Brighton
country: United Kingdom
facility: Royal Sussex County Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrooke'S Hospital
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital
city: Hull
country: United Kingdom
facility: Castle Hill Hospital
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospital
city: London
country: United Kingdom
facility: Royal Free London Nhs Foundation Trust
city: London
country: United Kingdom
facility: The Royal Marsden Nhs Foundation Trust - Chelsea
city: Manchester
country: United Kingdom
facility: The Christie Nhs Foundation Trust Uk
city: Oxford
country: United Kingdom
facility: Churchill Hospital
city: Preston
country: United Kingdom
facility: Royal Preston Hospital
city: Sutton
country: United Kingdom
facility: The Royal Marsden Nhs Foundation Trust - Sutton
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital Truro Sunrise Centre
Study officials:
References:
citation: Rao S, Jones M, Bowman J, Tian C, Spano JP. POD1UM-303/InterAACT 2: A phase III, global, randomized, double-blind study of retifanlimab or placebo plus carboplatin-paclitaxel in patients with locally advanced or metastatic squamous cell anal carcinoma. Front Oncol. 2022 Aug 24;12:935383. doi: 10.3389/fonc.2022.935383. eCollection 2022.