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

Non-Small Cell Lung Cancer Clinical Trial

— Krascendo 170  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05789082
• Other study ID #: BO44426
• Secondary ID: 2022-003048-2820
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 20, 2023
• Est. completion date: September 30, 2025

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: BO44426 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S. and Canada)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 96
• Est. completion date: September 30, 2025
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• Divarasib
Participants will receive one of two doses of divarasib orally (PO), QD on days 1-21 of each 21-day cycle.
• Pembrolizumab
Participants will receive a 200 mg IV infusion of pembrolizumab Q3W on Day 1 of each 21-day cycle.
• Carboplatin
Participants will receive IV carboplatin Q3W for four 21-day cycles.
• Cisplatin
Participants will receive IV cisplatin Q3W for four 21-day cycles.
• Pemetrexed
Participants will receive IV pemetrexed Q3W.

Locations

Country	Name	City	State
Argentina	Hospital Britanico; Oncologia	Buenos Aires
Argentina	Clinica Adventista Belgrano; Oncology	Ciudad Autonoma Buenos Aires
Argentina	Centro Oncologico Riojano Integral (CORI)	La Rioja
Australia	Concord Repatriation General Hospital; Concord Cancer Centre	Concord	New South Wales
Australia	Alfred Health	Melbourne	Victoria
Australia	Peter MacCallum Cancer Centre; Medical Oncology	Melbourne	Victoria
Belgium	Cliniques Universitaires St-Luc	Bruxelles
Belgium	Jessa Zkh (Campus Virga Jesse)	Hasselt
Belgium	Clinique Ste-Elisabeth	Namur
Belgium	AZ Delta (Campus Rumbeke)	Roeselare
Brazil	Hospital de Cancer de Barretos	Barretos	SP
Brazil	Crio - Centro Regional Integrado de Oncologia	Fortaleza	CE
Brazil	Hospital Nossa Senhora da Conceicao	Porto Alegre	RS
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP	Sao Paulo	SP
Canada	Jewish General Hospital	Montreal	Quebec
Canada	Princess Margaret Cancer Center	Toronto	Ontario
China	Hunan Cancer Hospital	Changsha CITY
China	Harbin Medical University Cancer Hospital	Harbin
China	Shanghai Pulmonary Hospital	Shanghai
Israel	Rambam Medical Center; Oncology	Haifa
Israel	Rabin MC; Davidof Center - Oncology Institute	Petach Tikva
Israel	Tel Aviv Sourasky Medical Ctr; Oncology	Tel Aviv
Italy	Istituto Nazionale Tumori Fondazione G. Pascale	Napoli	Campania
Italy	A.O. UNIVERSITARIA S. LUIGI GONZAGA; Oncologia Medica	Orbassano	Piemonte
Italy	Policlinico Universitario Agostino Gemelli IRCCS; UOS Fase 1	Roma	Lazio
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Netherlands	NKI The Netherlands Cancer Institute	Amsterdam
Netherlands	UMC St Radboud	Nijmegen
Poland	Uniwersyteckie Centrum Kliniczne; Osrodek Badan Wczesnych Faz	Gda?sk
Poland	Krakowski Szpital Specjalistyczny im sw. Jana Paw?a II; Oddzia? Onkologiczny	Kraków
Poland	Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie; Oddzial onkologii z pododdzialem chemioterapii	Olsztyn
Spain	ICO Badalona-H.U. Germans Trias i Pujol	Badalona	Barcelona
Spain	Vall d?Hebron Institute of Oncology (VHIO), Barcelona	Barcelona
Spain	Hospital General Universitario Gregorio Marañon; Servicio de Oncologia	Madrid
Spain	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid
Spain	NEXT Oncology-Hospital Quironsalud Madrid	Pozuelo de Alarcon	Madrid
Spain	Hospital Universitario Virgen del Rocio; Servicio de Oncologia	Sevilla
Sweden	Sahlgrenska University Hospital; Sahlgrenska Clinical Trial unit / Department of Oncology	Göteborg
Switzerland	Universitätsspital Basel; Oncology - Klinische Forschung	Basel
Switzerland	Inselspital Bern; Universitätsklinik für Medizinische Onkologie, Klinische Forschungseinheit	Bern
Taiwan	National Cheng Kung University Hospital; Internal Medicine	North Dist.
Taiwan	Taichung Veterans General Hospital; Dept of Internal Medicine	Taichung
Taiwan	National Taiwan Uni Hospital; Internal Medicine	Taipei
Taiwan	Chang Gung Medical Foundation - Linkou; Chest Dept	Taoyuan
Turkey	Adana City Hospital, Medical Oncology	Adana
Turkey	Ankara Bilkent City Hospital	Ankara
Turkey	Koc University Hospital; Oncology	Istanbul
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Barts & London School of Med; Medical Oncology	London
United States	NYU Langone Hospital - Long Island	Mineola	New York
United States	Yale Cancer Center	New Haven	Connecticut
United States	NYU Cancer Center; NYU Cancer Institute	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  China,  Israel,  Italy,  Korea, Republic of,  Netherlands,  Poland,  Spain,  Sweden,  Switzerland,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with Adverse Events (AEs)		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	Objective Response Rate (ORR)	The percentage of participants who experience a complete response or partial response, as determined by the investigator, according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	Up to approximately 3 years
Secondary	Duration of Response (DOR)	The time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1	Up to approximately 3 years
Secondary	Progression Free Survival (PFS)	The time from randomization, or date of first treatment for participants enrolled prior to the expansion stage, to the first occurrence of disease progression or death from any cause during the study (whichever occurs first), as determined by the investigator according to RECIST v1.1	Up to approximately 3 years
Secondary	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)		Up to approximately 3 years
Secondary	Change from Baseline in Symptomatic Side Effects, as Assessed Through use of the PRO-CTCAE		Baseline up to approximately 3 years
Secondary	Percentage of Participants Reporting "Frequent" or "Almost Constant" Diarrhea During the First Three Cycles of Treatment According to the PRO-CTCAE Criteria		Up to approximately 3 years
Secondary	Percentage of Participants Reporting "Severe" or "Very Severe" Nausea or Vomiting During the First Three Cycles of Treatment According to the PRO-CTCAE		Up to approximately 3 years
Secondary	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)		Up to approximately 3 years
Secondary	Plasma Concentration of Divarasib at Specified Timepoints		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	Identification of Divarasib Recommended Dose	The recommended dose will be based upon the totality of safety, activity, and PK data.	Up to approximately 3 years