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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05789082




Registration number
NCT05789082
Ethics application status
Date submitted
21/02/2023
Date registered
29/03/2023

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
2022-003048-28
Secondary ID [2] 0 0
BO44426
Universal Trial Number (UTN)
Trial acronym
Krascendo 170
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Small Cell 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 - Pembrolizumab
Treatment: Drugs - Carboplatin
Treatment: Drugs - Cisplatin
Treatment: Drugs - Pemetrexed

Experimental: Cohort A - Combination Dose Finding + Dose Expansion - Participants enrolled in this cohort will receive divarasib (different dose levels will be evaluated) once a day (QD) combined with pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W).

During the expansion stage, some participants are planned to be randomized to one divarasib combination dose level; other participants are planned to be randomized to another divarasib combination dose level. Divarasib will be given in combination with pembrolizumab.

Experimental: Cohort B - Combination Dose Finding + Dose Expansion - Participants enrolled in this cohort will receive divarasib (different dose levels will be evaluated) QD combined with pembrolizumab 200 mg IV Q3W plus investigator's choice of platinum-based chemotherapy (carboplatin or cisplatin) and pemetrexed.


Treatment: Drugs: Divarasib
Participants will receive one of two doses of divarasib orally (PO), QD on days 1-21 of each 21-day cycle.

Treatment: Drugs: Pembrolizumab
Participants will receive a 200 mg IV infusion of pembrolizumab Q3W on Day 1 of each 21-day cycle.

Treatment: Drugs: Carboplatin
Participants will receive IV carboplatin Q3W for four 21-day cycles.

Treatment: Drugs: Cisplatin
Participants will receive IV cisplatin Q3W for four 21-day cycles.

Treatment: Drugs: Pemetrexed
Participants will receive IV pemetrexed Q3W.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants with Adverse Events (AEs)
Timepoint [1] 0 0
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 outcome [1] 0 0
Objective Response Rate (ORR)
Timepoint [1] 0 0
Up to approximately 3 years
Secondary outcome [2] 0 0
Duration of Response (DOR)
Timepoint [2] 0 0
Up to approximately 3 years
Secondary outcome [3] 0 0
Progression Free Survival (PFS)
Timepoint [3] 0 0
Up to approximately 3 years
Secondary outcome [4] 0 0
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)
Timepoint [4] 0 0
Up to approximately 3 years
Secondary outcome [5] 0 0
Change from Baseline in Symptomatic Side Effects, as Assessed Through use of the PRO-CTCAE
Timepoint [5] 0 0
Baseline up to approximately 3 years
Secondary outcome [6] 0 0
Percentage of Participants Reporting "Frequent" or "Almost Constant" Diarrhea During the First Three Cycles of Treatment According to the PRO-CTCAE Criteria
Timepoint [6] 0 0
Up to approximately 3 years
Secondary outcome [7] 0 0
Percentage of Participants Reporting "Severe" or "Very Severe" Nausea or Vomiting During the First Three Cycles of Treatment According to the PRO-CTCAE
Timepoint [7] 0 0
Up to approximately 3 years
Secondary outcome [8] 0 0
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)
Timepoint [8] 0 0
Up to approximately 3 years
Secondary outcome [9] 0 0
Plasma Concentration of Divarasib at Specified Timepoints
Timepoint [9] 0 0
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.
Secondary outcome [10] 0 0
Identification of Divarasib Recommended Dose
Timepoint [10] 0 0
Up to approximately 3 years

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

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 1
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
20/06/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/09/2025
Actual
Sample size
Target
96
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Concord Repatriation General Hospital; Concord Cancer Centre - Concord
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Centre; Medical Oncology - Melbourne
Recruitment hospital [3] 0 0
Alfred Health - Melbourne
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
Argentina
State/province [5] 0 0
Buenos Aires
Country [6] 0 0
Argentina
State/province [6] 0 0
Ciudad Autonoma Buenos Aires
Country [7] 0 0
Argentina
State/province [7] 0 0
La Rioja
Country [8] 0 0
Belgium
State/province [8] 0 0
Bruxelles
Country [9] 0 0
Belgium
State/province [9] 0 0
Hasselt
Country [10] 0 0
Belgium
State/province [10] 0 0
Namur
Country [11] 0 0
Belgium
State/province [11] 0 0
Roeselare
Country [12] 0 0
Brazil
State/province [12] 0 0
CE
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
Canada
State/province [15] 0 0
Ontario
Country [16] 0 0
Canada
State/province [16] 0 0
Quebec
Country [17] 0 0
China
State/province [17] 0 0
Changsha CITY
Country [18] 0 0
China
State/province [18] 0 0
Harbin
Country [19] 0 0
China
State/province [19] 0 0
Shanghai
Country [20] 0 0
Israel
State/province [20] 0 0
Haifa
Country [21] 0 0
Israel
State/province [21] 0 0
Petach Tikva
Country [22] 0 0
Israel
State/province [22] 0 0
Tel Aviv
Country [23] 0 0
Italy
State/province [23] 0 0
Campania
Country [24] 0 0
Italy
State/province [24] 0 0
Lazio
Country [25] 0 0
Italy
State/province [25] 0 0
Lombardia
Country [26] 0 0
Italy
State/province [26] 0 0
Piemonte
Country [27] 0 0
Korea, Republic of
State/province [27] 0 0
Busan
Country [28] 0 0
Korea, Republic of
State/province [28] 0 0
Seoul
Country [29] 0 0
Netherlands
State/province [29] 0 0
Amsterdam
Country [30] 0 0
Netherlands
State/province [30] 0 0
Nijmegen
Country [31] 0 0
Poland
State/province [31] 0 0
Gda?sk
Country [32] 0 0
Poland
State/province [32] 0 0
Kraków
Country [33] 0 0
Poland
State/province [33] 0 0
Olsztyn
Country [34] 0 0
Spain
State/province [34] 0 0
Barcelona
Country [35] 0 0
Spain
State/province [35] 0 0
Madrid
Country [36] 0 0
Spain
State/province [36] 0 0
Sevilla
Country [37] 0 0
Spain
State/province [37] 0 0
Valencia
Country [38] 0 0
Sweden
State/province [38] 0 0
Göteborg
Country [39] 0 0
Switzerland
State/province [39] 0 0
Basel
Country [40] 0 0
Switzerland
State/province [40] 0 0
Bern
Country [41] 0 0
Taiwan
State/province [41] 0 0
North Dist.
Country [42] 0 0
Taiwan
State/province [42] 0 0
Taichung
Country [43] 0 0
Taiwan
State/province [43] 0 0
Taipei
Country [44] 0 0
Taiwan
State/province [44] 0 0
Taoyuan
Country [45] 0 0
Turkey
State/province [45] 0 0
Adana
Country [46] 0 0
Turkey
State/province [46] 0 0
Ankara
Country [47] 0 0
Turkey
State/province [47] 0 0
Istanbul
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Glasgow
Country [49] 0 0
United Kingdom
State/province [49] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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: BO44426 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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05789082