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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06497556




Registration number
NCT06497556
Ethics application status
Date submitted
5/07/2024
Date registered
11/07/2024
Date last updated
29/10/2024

Titles & IDs
Public title
A Study Evaluating the Efficacy and Safety of Divarasib Versus Sotorasib or Adagrasib in Participants With Previously Treated KRAS G12C-positive Advanced or Metastatic Non-Small Cell Lung Cancer
Scientific title
A Phase III, Randomized, Open-Label, Multicenter Study Evaluating the Efficacy and Safety of Divarasib Versus Sotorasib or Adagrasib in Patients With Previously Treated KRAS G12C-Positive Advanced or Metastatic Non-Small Cell Lung Cancer
Secondary ID [1] 0 0
2024-510908-37-00
Secondary ID [2] 0 0
BO45217
Universal Trial Number (UTN)
Trial acronym
Krascendo 1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Small Cell Lung Cancer 0 0
KRAS G12C Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Divarasib
Treatment: Drugs - Sotorasib
Treatment: Drugs - Adagrasib

Experimental: Divarasib - Participants will receive divarasib orally, once daily (QD).

Active comparator: KRAS G12C inhibitor - Participants will receive Sotorasib orally QD or adagrasib orally twice a day (BID)


Treatment: Drugs: Divarasib
Divarasib will be administered orally QD

Treatment: Drugs: Sotorasib
Sotorasib will be administered orally QD

Treatment: Drugs: Adagrasib
Adagrasib will be administred orally BID
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-Free Survival (PFS)
Timepoint [1] 0 0
Up to approximately 4 years
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Up to approximately 4 years
Secondary outcome [2] 0 0
Time to Confirmed Deterioration (TTCD) on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Dyspnea Item and Physical Functioning Scale
Timepoint [2] 0 0
Baseline up to approximately 4 years
Secondary outcome [3] 0 0
TTCD on the EORTC Quality-of-Life Questionnaire-Supplemental Lung Cancer Module (QLQ-LC13) Cough Scale
Timepoint [3] 0 0
Baseline up to approximately 4 years
Secondary outcome [4] 0 0
Percentage of Participants with Objective Response Rate (ORR)
Timepoint [4] 0 0
From randomization up to approximately 4 years
Secondary outcome [5] 0 0
Duration of Response (DOR)
Timepoint [5] 0 0
Up to approximately 4 years
Secondary outcome [6] 0 0
Percentage of Participants with Adverse Events (AEs)
Timepoint [6] 0 0
Up to approximately 4 years
Secondary outcome [7] 0 0
Number of Participants Reporting Presence, Frequency, Severity, and/or Degree of Interference with Daily Function of Symptomatic Treatment Toxicities Assessed by NCI Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE)
Timepoint [7] 0 0
Up to approximately 4 years
Secondary outcome [8] 0 0
Change from Baseline in Diarrhea, Nausea, Vomiting, Anorexia, Alopecia, Dyspnea, Cough, Constipation, Myalgia, Headache, and Rash/Acne as Assessed Through use of the NCI PRO-CTCAE
Timepoint [8] 0 0
Baseline up to approximately 4 years
Secondary outcome [9] 0 0
Frequency of Participants' Response of the Degree they are Troubled with Treatment Symptoms, as Assessed Through use of the single-item EORTC Item List (IL46)
Timepoint [9] 0 0
Up to approximately 4 years
Secondary outcome [10] 0 0
Change from Baseline in Cough, Chest Pain, Dyspnea, Physical and Role Functioning, and Global Health Status score/Quality of Life Score (GHS/QoL) at Each Timepoint as Assessed Through use of the EORTC QLQ-LC13 and QLQ-C30
Timepoint [10] 0 0
Baseline up to approximately 4 years
Secondary outcome [11] 0 0
TTCD on the EORTC QLQ-C30 Role Functioning and GHS/QoL scales
Timepoint [11] 0 0
Up to approximately 4 years
Secondary outcome [12] 0 0
TTCD on the Chest Pain Scale of the QLQ-LC13 Scales
Timepoint [12] 0 0
Up to approximately 4 years

Eligibility
Key inclusion criteria
* Unequivocal histologically or cytologically confirmed diagnosis of unresectable Stage IIIc, per the American Joint Committee on Cancer staging system (AJCC) (Amin et al. 2017) not amenable to treatment with combined modality chemoradiation (advanced) or Stage IV (metastatic) NSCLC
* Disease progression during or after treatment with at least one prior systemic therapy but no more than three lines of prior systemic therapy in the metastatic setting
* Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
* Documentation of the presence of a KRAS G12C mutation
* Availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or 10-15 (15 preferred) unstained, freshly cut, serial slides with an associated pathology report
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Life expectancy of >= 12 weeks
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Known hypersensitivity to any of the components of divarasib, or sotorasib or adagrasib
* Malabsorption syndrome or other condition that would interfere with enteral absorption
* Known concomitant second oncogenic driver
* Mixed small-cell lung cancer or large cell neuroendocrine histology
* Known and untreated, or active central nervous system (CNS) metastases
* Leptomeningeal disease or carcinomatous meningitis
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures biweekly or more frequently
* Any infection that, in the opinion of the investigator, could impact patient safety, or treatment with therapeutic oral or IV antibiotics within 14 days prior to Day 1 of Cycle 1
* Prior treatment with any KRAS G12C inhibitor or pan-KRAS/RAS inhibitor
* More than 30 Gy of radiotherapy to the lung within 6 months of randomization
* Uncontrolled tumor-related pain
* Unresolved toxicities from prior anticancer therapy
* History of malignancy within 5 years prior to screening, with the exception of the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate >90%), such as adequately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/09/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/09/2029
Actual
Sample size
Target
320
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Kinghorn Cancer Centre; St Vincents Hospital - Darlinghurst
Recruitment hospital [2] 0 0
GenesisCare North Shore - St Leonards
Recruitment hospital [3] 0 0
Sunshine Coast University Hospital; The Adem Crosby Centre - Birtinya
Recruitment hospital [4] 0 0
Lyell McEwin Hospital; Clinical Trials Unit - Elizabeth Vale
Recruitment hospital [5] 0 0
Peter Maccallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment postcode(s) [3] 0 0
4575 - Birtinya
Recruitment postcode(s) [4] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [5] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Maine
Country [4] 0 0
United States of America
State/province [4] 0 0
Nebraska
Country [5] 0 0
United States of America
State/province [5] 0 0
South Dakota
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Argentina
State/province [8] 0 0
Buenos Aires
Country [9] 0 0
Argentina
State/province [9] 0 0
Ciudad Autonoma Buenos Aires
Country [10] 0 0
Brazil
State/province [10] 0 0
BA
Country [11] 0 0
Brazil
State/province [11] 0 0
DF
Country [12] 0 0
Brazil
State/province [12] 0 0
RJ
Country [13] 0 0
Brazil
State/province [13] 0 0
RS
Country [14] 0 0
Brazil
State/province [14] 0 0
SP
Country [15] 0 0
Denmark
State/province [15] 0 0
Aarhus N
Country [16] 0 0
France
State/province [16] 0 0
Montpellier
Country [17] 0 0
France
State/province [17] 0 0
Strasbourg
Country [18] 0 0
France
State/province [18] 0 0
Toulouse
Country [19] 0 0
Germany
State/province [19] 0 0
Essen
Country [20] 0 0
Germany
State/province [20] 0 0
Esslingen
Country [21] 0 0
Germany
State/province [21] 0 0
Halle
Country [22] 0 0
Germany
State/province [22] 0 0
Homburg
Country [23] 0 0
Germany
State/province [23] 0 0
Immenhausen
Country [24] 0 0
Germany
State/province [24] 0 0
Münster
Country [25] 0 0
Germany
State/province [25] 0 0
Regensburg
Country [26] 0 0
Hong Kong
State/province [26] 0 0
Hong Kong
Country [27] 0 0
Italy
State/province [27] 0 0
Sicilia
Country [28] 0 0
Korea, Republic of
State/province [28] 0 0
Busan
Country [29] 0 0
Korea, Republic of
State/province [29] 0 0
Cheongju-si
Country [30] 0 0
Korea, Republic of
State/province [30] 0 0
Daegu
Country [31] 0 0
Korea, Republic of
State/province [31] 0 0
Gyeonggi-do
Country [32] 0 0
Korea, Republic of
State/province [32] 0 0
Gyeongsangnam-do
Country [33] 0 0
Korea, Republic of
State/province [33] 0 0
Incheon
Country [34] 0 0
Korea, Republic of
State/province [34] 0 0
Jeollanam-do
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Seongnam-si
Country [36] 0 0
Korea, Republic of
State/province [36] 0 0
Seoul
Country [37] 0 0
Poland
State/province [37] 0 0
?ód?
Country [38] 0 0
Poland
State/province [38] 0 0
Lublin
Country [39] 0 0
Poland
State/province [39] 0 0
Olsztyn
Country [40] 0 0
Poland
State/province [40] 0 0
Poznan
Country [41] 0 0
Poland
State/province [41] 0 0
Radom
Country [42] 0 0
Poland
State/province [42] 0 0
Warszawa
Country [43] 0 0
Sweden
State/province [43] 0 0
Gävle
Country [44] 0 0
Taiwan
State/province [44] 0 0
Kaohsiung City
Country [45] 0 0
Taiwan
State/province [45] 0 0
Taichung
Country [46] 0 0
Taiwan
State/province [46] 0 0
Taipei
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Glasgow
Country [48] 0 0
United Kingdom
State/province [48] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Chugai Pharmaceutical
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to assess the safety and efficacy of divarasib compared to locally approved KRAS G12C inhibitors (sotorasib or adagrasib) in participants with KRAS G12C-positive (KRAS G12C +) advanced or metastatic non-small cell lung cancer (NSCLC).
Trial website
https://clinicaltrials.gov/study/NCT06497556
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Reference Study ID Number: BO45217 https://forpatients.roche.com/
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. and Canada)
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06497556