Clinical trial NCT05198934: Sotorasib and Panitumumab Versus Investigator's Choice for Participants With Kirsten Rat Sarcoma (KRAS) p.G12C Mutation
Official title: A Phase 3 Multicenter, Randomized, Open-label, Active-controlled Study of Sotorasib and Panitumumab Versus Investigator's Choice (Trifluridine and Tipiracil, or Regorafenib) for the Treatment of Previously Treated Metastatic Colorectal Cancer Subjects With Kirsten Rat Sarcoma (KRAS) p.G12C Mutation
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Colorectal Cancer (CRC)
Keywords: Sotorasib
AMG 510
Panitumumab
Metastatic colorectal cancer
Kirsten rat sarcoma p.G12C mutation
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2022-01-20
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of the study is to compare progression-free survival (PFS) in previously treated participants with Kirsten rat sarcoma (KRAS) p.G12C mutated colorectal cancer (CRC) receiving sotorasib 240 mg once daily (QD) and panitumumab vs investigator's choice (trifluridine and tipiracil, or regorafenib), and sotorasib 960 mg QD and panitumumab vs investigator's choice (trifluridine and tipiracil, or regorafenib).


Eligibility criteria: Inclusion Criteria:

* Participant has provided informed consent/assent prior to initiation of any study specific activities/procedures.
* Age ≥18 years.
* Pathologically documented metastatic colorectal adenocarcinoma with Kirsten rat sarcoma (KRAS) p.G12C mutation as determined by prospective central testing, using the analytically validated Qiagen Therascreen KRAS RGQ polymerase chain reaction Kit in CRC as an investigational device demonstrating a KRAS p.G12C mutation is present. Local testing and documentation of KRAS p.G12C mutation should have been previously performed as part of standard of care.
* Participants will have received at least 1 prior line of therapy for metastatic disease. Participants must have received and progressed or experienced disease recurrence on or after fluoropyrimidine, irinotecan, and oxaliplatin given for metastatic disease unless the participant, in the opinion of the investigator, is not a candidate for fluoropyrimidine, irinotecan, or oxaliplatin, in which case, the participant may be eligible after investigator discussion with Amgen medical monitor provided participant has received at least one prior line of therapy for metastatic disease and provided trifluridine and tipiracil or regorafenib is deemed the appropriate next line of therapy for the participant.
* Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria. Lesions previously radiated are not considered measurable unless they have progressed after radiation.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤2.
* Life expectancy of \>3 months, in the opinion of the investigator.
* Adequate hematologic and end-organ function, defined as the following within 2 weeks prior to cycle 1 day 1:

  * Absolute neutrophil count (ANC) ≥1.5 x 10\^9/L (without granulocyte colony stimulating factor support within 2 weeks of laboratory test used to determine eligibility).
  * Hemoglobin ≥9.0 g/dL (without transfusion within 2 weeks of laboratory test used to determine eligibility).
  * Platelet count ≥100 x 10\^9/L (without transfusion within 2 weeks of laboratory test used to determine eligibility).
  * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 times the upper limit of normal (ULN).
  * Serum bilirubin ≤1.0 x ULN. For participants with Gilbert's disease, total bilirubin or direct bilirubin needs to be ≤1.0 x ULN.
  * International normalized ratio (INR) and activated partial thromboplastin time (or partial thromboplastin time) ≤1.5 x ULN. Prothrombin time (PT) ≤1.5 x ULN may be used instead of INR for sites whose labs do not report INR.
  * Estimated glomerular filtration rate based on Modification of Diet in Renal Disease (MDRD) calculation ≥30 mL/min/1.73 m\^2.
* Fridericia's Correction Formula (QTcF) ≤470 msec.

Exclusion Criteria:

* Active brain metastases. Participants who have had brain metastases resected or have received radiation therapy ending at least 4 weeks prior to study day 1 are eligible if they meet all of the following criteria: a) residual neurological symptoms grade ≤2; b) on stable doses of dexamethasone or equivalent for at least 2 weeks, if applicable; and c) follow-up magnetic resonance imaging (MRI) performed within 28 days of day 1 shows no progression or new lesions appearing.
* History or presence of hematological malignancies unless curatively treated with no evidence of disease ≥2 years.
* History of other malignancy within the past 3 years, with the following exceptions:

  * Malignancy treated with curative intent and with no known active disease present for ≥3 years before enrollment and felt to be at low risk for recurrence by the treating physician.
  * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
  * Adequately treated cervical carcinoma in situ without evidence of disease.
  * Adequately treated breast ductal carcinoma in situ without evidence of disease.
  * Prostatic intraepithelial neoplasia without evidence of prostate cancer.
  * Adequately treated urothelial papillary non-invasive carcinoma or carcinoma in situ.
* Leptomeningeal disease.
* Significant gastrointestinal (GI) disorder that results in significant malabsorption, requirement for intravenous (IV) alimentation, or inability to take oral medication.
* History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis.
* Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 6 months prior to randomization, unstable arrhythmias or unstable angina.
* Previous treatment with a KRAS G12C inhibitor.

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Approximately 3 years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Approximately 3 years
measure: Objective Response Rate (ORR)
timeFrame: Approximately 3 years
measure: Duration of Response (DOR)
timeFrame: Approximately 3 years
measure: Time to Response (TTR)
timeFrame: Approximately 3 years
measure: Disease Control Rate (DCR)
timeFrame: Approximately 3 years
measure: Investigator Assessed ORR
timeFrame: Approximately 3 years
measure: Investigator Assessed PFS
timeFrame: Approximately 3 years
measure: Number of Participants with a Treatment-emergent Adverse Event (TEAE)
timeFrame: Approximately 3 years
measure: Change from Baseline in Fatigue Severity as Measured by Item 3 of the Brief Fatigue Inventory (BFI)
timeFrame: Baseline and Week 8
measure: Change from Baseline in Pain Severity as Measured by Item 3 of the Brief Pain Inventory (BPI)
timeFrame: Baseline and Week 8
measure: Change from Baseline in Physical Functioning as Measured by the Physical Function Domain of the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire-Core Questionnaire (EORTC QLQ-C30)
timeFrame: Baseline and Week 8
measure: Change from Baseline in Global Health Status as Measured by Questions 29 and 30 of the EORTC QLQ-C30
timeFrame: Baseline and Week 8
measure: Change from Baseline For All Subscales of the BFI
timeFrame: Baseline and Week 8
measure: Change from Baseline For All Subscales of the BPI
timeFrame: Baseline and Week 8
measure: Change from Baseline For All Subscales and Domains of EORTC QLQ-C30
timeFrame: Baseline and Week 8
measure: Change from Baseline in Visual Analog Scale (VAS) Scores as Measured by EuroQol-5D level 5 (EQ-5D-5L)
timeFrame: Baseline and Week 8
measure: Average Score on Single Question on Symptom Bother GP5 from Functional Assessment of Cancer Therapy - General (FACT-G)
timeFrame: Approximately 2 years
measure: Average Score of Patient Global Impression of Change (PGIC)
timeFrame: Approximately 2 years
measure: Maximum Plasma Concentration (Cmax) of Sotorasib
timeFrame: Day 1 to approximately 2 years
measure: Cmax of Panitumumab
timeFrame: Day 1 to approximately 2 years
measure: Area Under the Plasma Concentration-time Curve (AUC) of Sotorasib
timeFrame: Day 1 to approximately 2 years
measure: AUC of Panitumumab
timeFrame: Day 1 to approximately 2 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Central Alabama Research
state: Alabama
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Orange
country: United States
facility: University of California Irvine
state: California
city: Washington
country: United States
facility: Johns Hopkins University School of Medicine
state: District of Columbia
city: Jacksonville
country: United States
facility: Cancer Specialists of North Florida
state: Florida
city: Miami Lakes
country: United States
facility: Lakes Research LLC
state: Florida
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers PC
state: Georgia
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Farmington Hills
country: United States
facility: Revive Research Institute
state: Michigan
city: Lansing
country: United States
facility: Sparrow Clinical Research Institute
state: Michigan
city: Sterling Heights
country: United States
facility: Revive Research Institute
state: Michigan
city: Syracuse
country: United States
facility: Upstate University Hospital
state: New York
city: White Plains
country: United States
facility: White Plains Hospital Center for Cancer Care
state: New York
city: Greensboro
country: United States
facility: Moses H Cone Memorial Hospital
state: North Carolina
city: Columbus
country: United States
facility: The Mark H Zangmeister Center
state: Ohio
city: Lancaster
country: United States
facility: Lancaster General Hospital Ann B Barshinger Cancer Institute
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: Kelsey Research Foundation
state: Texas
city: Houston
country: United States
facility: Best Cancer Care & Hematology
state: Texas
city: Kingwood
country: United States
facility: Lumi Research
state: Texas
city: Camperdown
country: Australia
facility: Chris OBrien Lifehouse
state: New South Wales
city: St Leonards
country: Australia
facility: GenesisCare -North Shore (Oncology)
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Woodville South
country: Australia
facility: The Queen Elizabeth Hospital
state: South Australia
city: Lyon Cédex 3
country: France
facility: Centre Hospitalier Universitaire de Lyon - Hopital Edouard Herriot
city: Montpellier Cedex 5
country: France
facility: Institut regional du Cancer Montpellier
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Pessac
country: France
facility: Hôpital Haut -lévêque
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin, Charité Campus Virchow-Klinikum
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus an der Technischen Universitaet Dresden
city: Goettingen
country: Germany
facility: Universitaetsmedizin Goettingen - Georg-August-Universitaet
city: Muenchen
country: Germany
facility: Klinikum der Universitaet Muenchen Campus Grosshadern
city: Tuebingen
country: Germany
facility: Universitaetsklinikum der Eberhard Karls Universitaet Tuebingen
city: Athens
country: Greece
facility: General Hospital of Athens Laiko
city: Athens
country: Greece
facility: Evgenidio Hospital I Agia Trias
city: Athens
country: Greece
facility: Hygeia Hospital
city: Heraklion - Crete
country: Greece
facility: University Hospital of Heraklion
city: Patra
country: Greece
facility: University Hospital of Patras
city: Thessaloniki
country: Greece
facility: Theagenion Anticancer Hospital
city: Thessaloniki
country: Greece
facility: Agios Loukas Clinic
city: Brescia
country: Italy
facility: Istituto Ospedaliero Fondazione Poliambulanza
city: Catania
country: Italy
facility: Azienda Ospedaliera Rilievo Nazionale e Alta Specializzazione Garibaldi Nesima
city: Confreria (CN)
country: Italy
facility: Azienda Ospedaliera Santa Croce e Carle
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
city: Genova
country: Italy
facility: Ospedale Policlinico San Martino IRCCS
city: La Spezia
country: Italy
facility: Azienda Sanitaria Locale 5 Spezzino Ospedale S Andrea
city: Lecce
country: Italy
facility: Azienda Unita Sanitaria Locale LE Presidio Ospedaliero Vito Fazzi Polo Oncologico Giovanni Paolo II
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Milano
country: Italy
facility: Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
city: Monserrato CA
country: Italy
facility: Azienda Ospedaliero Universitaria di Cagliari Policlinico Duilio Casula
city: Napoli
country: Italy
facility: Azienda Ospedaliero Universitaria Luigi Vanvitelli
city: Napoli
country: Italy
facility: Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione Giovanni Pascale
city: Novara
country: Italy
facility: Azienda Ospedaliero Universitaria Maggiore della Carita
city: Padova
country: Italy
facility: Istituto Oncologico Veneto IRCCS
city: Pisa
country: Italy
facility: Azienda Ospedaliera Universitaria Pisana Ospedale Santa Chiara
city: Potenza
country: Italy
facility: Azienda Ospedaliera San Carlo
city: Reggio Emilia
country: Italy
facility: Azienda Unita Sanitaria Locale di Reggio Emilia Arcispedale Santa Maria Nuova
city: Roma (RM)
country: Italy
facility: Fondazione Policlinico Tor Vergata
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli
city: Roma
country: Italy
facility: Azienda Ospedaliera San Giovanni Addolorata
city: Tricase
country: Italy
facility: Azienda Ospedaliera Cardinale Giovanni Panico
city: Vicenza
country: Italy
facility: Azienda Unita Locale Socio Sanitaria Berica 8
city: Nagakute-shi
country: Japan
facility: Aichi Medical University Hospital
state: Aichi
city: Chiba-shi
country: Japan
facility: Chiba Cancer Center
state: Chiba
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Matsuyama-shi
country: Japan
facility: National Hospital Organization Shikoku Cancer Center
state: Ehime
city: Fukuoka-shi
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
state: Fukuoka
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Akashi-shi
country: Japan
facility: Hyogo Cancer Center
state: Hyogo
city: Kawasaki-shi
country: Japan
facility: St Marianna University Hospital
state: Kanagawa
city: Yokohama-shi
country: Japan
facility: Kanagawa Prefectural Hospital Organization Kanagawa Cancer Center
state: Kanagawa
city: Osaka-shi
country: Japan
facility: National Hospital Organization Osaka National Hospital
state: Osaka
city: Suita-shi
country: Japan
facility: Osaka University Hospital
state: Osaka
city: Kitaadachi-gun
country: Japan
facility: Saitama Cancer Center
state: Saitama
city: Sunto-gun
country: Japan
facility: Shizuoka Cancer Center
state: Shizuoka
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Koto-ku
country: Japan
facility: The Cancer Institute Hospital of Japanese Foundation for Cancer Research
state: Tokyo
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Ciudad de Mexico
country: Mexico
facility: Superare Centro de Infusion SA de CV
state: Distrito Federal
city: Mexico City
country: Mexico
facility: Health Pharma Professional Research SA de CV
state: Distrito Federal
city: Ciudad de Mexico
country: Mexico
facility: Trials In Medicine SC
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
state: Andalucía
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves
state: Andalucía
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
state: Cantabria
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d Hebron
state: Cataluña
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
state: Cataluña
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
state: Comunidad Valenciana
city: Ourense
country: Spain
facility: Complexo Hospitalario Universitario de Ourense
state: Galicia
city: Pamplona
country: Spain
facility: Hospital Universitario de Navarra
state: Navarra
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: Royal Marsden Hospital
city: Maidstone
country: United Kingdom
facility: Maidstone Hospital
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Fakih MG, Salvatore L, Esaki T, Modest DP, Lopez-Bravo DP, Taieb J, Karamouzis MV, Ruiz-Garcia E, Kim TW, Kuboki Y, Meriggi F, Cunningham D, Yeh KH, Chan E, Chao J, Saportas Y, Tran Q, Cremolini C, Pietrantonio F. Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated KRAS G12C. N Engl J Med. 2023 Dec 7;389(23):2125-2139. doi: 10.1056/NEJMoa2308795. Epub 2023 Oct 22.