Clinical trial NCT05789082: A Study Evaluating the Safety, Activity, and Pharmacokinetics of Divarasib in Combination With Other Anti-Cancer Therapies in Participants With Previously Untreated Advanced or Metastatic Non-Small Cell Lung Cancer With a KRAS G12C Mutation
Official title: A Phase Ib/II, Open-Label, Multicenter Study Evaluating the Safety, Activity, and Pharmacokinetics of Divarasib in Combination With Other Anti-Cancer Therapies in Patients With Previously Untreated Advanced Or Metastatic Non-Small Cell Lung Cancer With a KRAS G12C Mutation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Non-Small Cell Lung Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2023-03-29
Enrollment: 240
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: The purpose of this study is to evaluate the safety, pharmacokinetics (PK), and activity of divarasib combined with other anti-cancer therapies in participants with previously untreated, advanced or metastatic non-small cell lung cancer (NSCLC).


Eligibility criteria: Inclusion Criteria:

* Confirmation of Biomarker eligibility
* Pre-treatment tumor tissue along with an associated pathology report is required for all participants enrolled on study. Representative tumor specimens must be in formalin-fixed, paraffin embedded (FFPE) blocks (preferred) or 15 unstained, freshly cut, serial slides. Although 15 slides are required, if only 10 slides are available, the participant may be eligible for the study following consultation with the Sponsor.
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
* Histologically or cytologically documented locally advanced unresectable or metastatic NSCLC that is not eligible for curative surgery and/or definitive chemoradiotherapy
* No prior systemic treatment for advanced unresectable or metastatic NSCLC
* Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Exclusion Criteria:

* Known concomitant second oncogenic driver with available targeted treatment
* Squamous cell histology NSCLC
* Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
* Prior treatment with a KRAS G12C inhibitor
* Known hypersensitivity to any of the components of divarasib or pembrolizumab; or known hypersensitivity to pemetrexed, carboplatin, or cisplatin (Cohort B only)
* History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis, active tuberculosis, significant cardiovascular disease within 3 months prior to initiation of study treatment
* History of malignancy other than NSCLC within 5 years prior to initiation of study treatment, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate more \>90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal breast carcinoma in situ, or Stage I uterine cancer
* Uncontrolled tumor related pain, pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures, uncontrolled or symptomatic hypercalcemia

Primary outcomes:
measure: Percentage of Participants with Adverse Events (AEs)
timeFrame: Baseline until 60 days after the final dose of study treatment or until initiation of another anti-cancer therapy, whichever occurs first (up to approximately 3 years)
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 3 years
measure: Duration of Response (DOR)
timeFrame: Up to approximately 3 years
measure: Progression Free Survival (PFS)
timeFrame: Up to approximately 3 years
measure: Number of Participants Reporting Presence, Frequency, Severity, and/or Degree of Interference with Daily Function of Symptomatic Side Effects as Assessed Through the Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE)
timeFrame: Up to approximately 3 years
measure: Change from Baseline in Symptomatic Side Effects, as Assessed Through use of the PRO-CTCAE
timeFrame: Baseline up to approximately 3 years
measure: Percentage of Participants Reporting "Frequent" or "Almost Constant" Diarrhea During the First Three Cycles of Treatment According to the PRO-CTCAE Criteria
timeFrame: Up to approximately 3 years
measure: Percentage of Participants Reporting "Severe" or "Very Severe" Nausea or Vomiting During the First Three Cycles of Treatment According to the PRO-CTCAE
timeFrame: Up to approximately 3 years
measure: Frequency of Participant's Response of the Degree they are Troubled with Treatment Symptoms, as Assessed Through use of the Single-item European Organisation for Research and Treatment of Cancer (EORTC) Item List 46 (IL46)
timeFrame: Up to approximately 3 years
measure: Plasma Concentration of Divarasib at Specified Timepoints
timeFrame: At Days 1, 8 and 15 of Cycles 1 and 2; Days 1 and 15 of Cycles 3 and 4; Day 1 of every other Cycle after Cycle 5, until treatment discontinuation (up to approximately 3 years). Each cycle is 21 days.
measure: Identification of Divarasib Recommended Dose
timeFrame: Up to approximately 3 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Huntington Beach
country: United States
facility: City of Hope - Seacliff
state: California
city: Irvine
country: United States
facility: City of Hope at Irvine Lennar
state: California
city: La Jolla
country: United States
facility: UCSD Moores Cancer Center
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Mineola
country: United States
facility: NYU Langone Hospital - Long Island
state: New York
city: New York
country: United States
facility: NYU Cancer Center
state: New York
city: New York
country: United States
facility: Mount SInai Medical Center
state: New York
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Blacksburg
country: United States
facility: Oncology & Hematology Associates of Southwest Virginia, Inc
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Buenos Aires
country: Argentina
facility: Hospital Britanico
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Clinica Adventista Belgrano
city: La Rioja
country: Argentina
facility: Centro Oncologico Riojano Integral (CORI)
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Health
state: Victoria
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Hasselt
country: Belgium
facility: Jessa Zkh (Campus Virga Jesse)
city: Namur
country: Belgium
facility: Clinique Ste-Elisabeth
city: Roeselare
country: Belgium
facility: AZ Delta (Campus Rumbeke)
city: Barretos
country: Brazil
facility: Hospital de Cancer de Barretos
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Instituto do Cancer do Estado de Sao Paulo - ICESP
state: São Paulo
city: Ottawa
country: Canada
facility: Ottawa Hospital Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Changsha CITY
country: China
facility: Hunan Cancer Hospital
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Petach Tikva
country: Israel
facility: Rabin MC
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Ctr
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione G. Pascale
state: Campania
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli IRCCS
state: Lazio
city: Milano
country: Italy
facility: Irccs Istituto Nazionale Dei Tumori (Int)
state: Lombardia
city: Orbassano
country: Italy
facility: A.O. Universitaria S. Luigi Gonzaga
state: Piemonte
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Amsterdam
country: Netherlands
facility: NKI The Netherlands Cancer Institute
city: Nijmegen
country: Netherlands
facility: UMC St Radboud
city: Gda?sk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Kraków
country: Poland
facility: Krakowski Szpital Specjalistyczny im sw. Jana Paw?a II
city: Olsztyn
country: Poland
facility: Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie
city: Badalona
country: Spain
facility: ICO Badalona-H.U. Germans Trias i Pujol
state: Barcelona
city: Barcelona
country: Spain
facility: Vall d?Hebron Institute of Oncology (VHIO), Barcelona
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: Basel
country: Switzerland
facility: Universitätsspital Basel
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan Uni Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation - Linkou
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: London
country: United Kingdom
facility: Barts & London School of Med
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: