Clinical trial • Phase I/II • Oncology
DIVARASIB for Non-small cell lung cancer | Advanced non-small cell lung cancer | Metastatic non-small cell lung cancer
Phase I/II trial of DIVARASIB for Non-small cell lung cancer | Advanced non-small cell lung cancer | Metastatic non-small cell lung cancer.
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- Non-small cell lung cancer | Advanced non-small cell lung cancer | Metastatic non-small cell lung cancer
- Trial Stage
- Phase I/II
- Drug Modality
- Small molecule | Monoclonal antibody
Key dates
- Initial CTIS Submission Date
- 23-04-2024
- First CTIS Authorization Date
- 27-05-2024
Trial design
open-label, none/not specified-controlled, adaptive Phase I/II trial in Sweden, Poland, Italy and others.
- Open Label
- Yes
- Comparator
- None/Not specified
- Adaptive
- True - study is designed with the intention to include new, additional treatment arms during study; includes Phase Ib dose-finding elements and aims to identify recommended dose based on safety, activity and PK data
- Biomarker Stratified
- True, KRAS G12C
- Single Multiple Or Escalation Dose Combined
- Yes
- Target Sample Size
- 124
Eligibility
Recruits 124 Vulnerable population selected in CTIS record (isVulnerablePopulationSelected = true). Subject information and informed consent documents include items such as 'L1_SIS BO44426 ICF infant authorization' and 'L1_SIS for the use and sharing of infant health information' (document titles present in CTIS document list), indicating specific procedures and documentation for infant/partner authorization; details on assent/consent processes (e.g., who provides consent) are provided in the ICF documents but are not explicitly described in the CTIS JSON record..
- Vulnerable Population
- Vulnerable population selected in CTIS record (isVulnerablePopulationSelected = true). Subject information and informed consent documents include items such as 'L1_SIS BO44426 ICF infant authorization' and 'L1_SIS for the use and sharing of infant health information' (document titles present in CTIS document list), indicating specific procedures and documentation for infant/partner authorization; details on assent/consent processes (e.g., who provides consent) are provided in the ICF documents but are not explicitly described in the CTIS JSON record.
Inclusion criteria
- {"criterion_text":"- Histologically or cytologically documented locally advanced unresectable or metastatic non-squamous NSCLC that is not eligible for curative surgery and/or definitive chemoradiotherapy"}
- {"criterion_text":"- No prior systemic treatment for advanced unresectable or metastatic NSCLC"}
- {"criterion_text":"- Adequate cardiovascular function as evidenced by the following: no significant cardiovascular disease within 3 months prior to initiation of study treatment and baseline corrected QT interval <=470 ms"}
- {"criterion_text":"- Pretreatment 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."}
- {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1"}
- {"criterion_text":"- Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1"}
Exclusion criteria
- {"criterion_text":"- Known concomitant second oncogenic driver with available targeted treatment"}
- {"criterion_text":"- Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases (Cohort A, B and C)"}
- {"criterion_text":"- Prior treatment with a KRAS G12C inhibitor"}
- {"criterion_text":"- Known hypersensitivity to any of the components of divarasib or pembrolizumab; or known hypersensitivity to pemetrexed, carboplatin, or cisplatin (Cohort B only)"}
- {"criterion_text":"- 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"}
- {"criterion_text":"- Uncontrolled tumor-related pain, pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures, uncontrolled or symptomatic hypercalcemia"}
- {"criterion_text":"- Significant cardiovascular disease within 3 months prior to initiation of study treatment , including any of the following: hypertensive crisis or encephalopathy; unstable angina; transient ischemic attack or stroke; congestive heart failure (NYHA class 2 or higher); serious cardiac arrythmia requiring treatment; history of thromboembolic events"}
Endpoints
Primary endpoints
- {"endpoint_text":"- 1. Occurrence of adverse events","definition_or_measurement_approach":""}
- {"endpoint_text":"- 2. Change from baseline at each visit in targeted safety parameters","definition_or_measurement_approach":"Change from baseline measured at each visit in targeted safety parameters (as stated)"}
Secondary endpoints
- {"endpoint_text":"- 1. Objective response rate","definition_or_measurement_approach":""}
- {"endpoint_text":"- 2. Duration of response","definition_or_measurement_approach":""}
- {"endpoint_text":"- 3. Progression free survival","definition_or_measurement_approach":""}
- {"endpoint_text":"- 4. CNS response defined as the percentage of participants who experience a complete response or partial response in the brain, as determined by the investigator according to modified RECIST (Cohort D Only)","definition_or_measurement_approach":"Determined by the investigator according to modified RECIST (Cohort D only)"}
- {"endpoint_text":"- 5. Change from baseline in symptomatic side effects, as assessed through use of the PRO-CTCAE","definition_or_measurement_approach":"Assessed using the Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE)"}
- {"endpoint_text":"- 6. Proportion of participants reporting \"frequent\" or \"almost constant\" diarrhea during the first three cycles of treatment according to the PRO-CTCAE criteria","definition_or_measurement_approach":"Reported by participants using PRO-CTCAE criteria during first three cycles"}
- {"endpoint_text":"- 7. Proportion of participants reporting \"severe\" or \"very severe\" nausea or vomiting during the first three cycles of treatment according to the PRO-CTCAE","definition_or_measurement_approach":"Reported by participants using PRO-CTCAE criteria during first three cycles"}
- {"endpoint_text":"- 8. 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)","definition_or_measurement_approach":"Assessed using the single-item EORTC Item List 46 (IL46)"}
- {"endpoint_text":"- 9. Plasma concentration of divarasib at specified timepoints","definition_or_measurement_approach":"Plasma concentration measurements of divarasib at specified pharmacokinetic timepoints"}
- {"endpoint_text":"- 10. Recommended dose of divarasib in combination with pembrolizumab (Cohort A) or pembrolizumab plus platinum-based chemotherapy and pemetrexed (Cohort B) based on the totality of safety, activity, and PK data","definition_or_measurement_approach":"Dose recommendation based on integrated safety, activity and PK data"}
- {"endpoint_text":"- 11. Presence, frequency of occurrence, severity, and/or degree of interference with daily function of symptomatic side effects as assessed through use of the Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO‑CTCAE)","definition_or_measurement_approach":"Assessed using PRO-CTCAE (presence, frequency, severity and interference with daily function)"}
Recruitment
- Planned Sample Size
- 124
- Recruitment Window Months
- 35
- Consent Approach
- Informed consent documents are provided (multiple L1_SIS and ICF documents listed in CTIS in multiple languages). Subject information and ICFs include language-specific and topic-specific documents (examples in document list: 'L1_SIS and ICF Main_EN', 'L1_SIS and ICF Main_FR', 'L1_SIS BO44426 ICF infant authorization', 'L1_SIS BO44426_ICF Pregnant partner', optional biopsy and lumbar puncture appendices). Consent is obtained via the provided ICFs; infant/partner authorization documents are present for related vulnerable situations. Specific age-based assent processes or exact consent signatory rules are provided in the ICF documents but are not detailed in the CTIS JSON.
Geography
- Total Number Of Sites
- 19
- Total Number Of Participants
- 116
Sweden
- Earliest CTIS Part Ii Submission Date
- 21-05-2024
- Latest Decision Or Authorization Date
- 28-05-2024
- Processing Time Days
- 7
- Number Of Sites
- 1
- Number Of Participants
- 4
Sites
- Site Name
- Sahlgrenska University Hospital-Vaestra Goetalandsregionen
- Department Name
- Verksamhet Onkologi, Klinisk Prövningsenhet Onkologi, Blå Stråket 2, 413 45 GÖTEBORG
- Principal Investigator Name
- Edvard Abel
- Principal Investigator Email
- edvard.abel@vgregion.se
- Contact Person Name
- Edvard Abel
- Contact Person Email
- edvard.abel@vgregion.se
Poland
- Earliest CTIS Part Ii Submission Date
- 21-05-2024
- Latest Decision Or Authorization Date
- 10-06-2024
- Processing Time Days
- 20
- Number Of Sites
- 3
- Number Of Participants
- 8
Sites
- Site Name
- Warminsko-Mazurskie Centrum Chorob Pluc W Olsztynie
- Department Name
- Oddział Onkologii z Pododdziałem Chemioterapii
- Principal Investigator Name
- Jarosław Kołb-Sielecki
- Principal Investigator Email
- sekretariat@pulmonologia.olsztyn.pl
- Contact Person Name
- Jarosław Kołb-Sielecki
- Contact Person Email
- sekretariat@pulmonologia.olsztyn.pl
- Site Name
- Uniwersyteckie Centrum Kliniczne
- Department Name
- Ośrodek Badań Klinicznych Wczesnych Faz
- Principal Investigator Name
- Rafał Dziadziuszko
- Principal Investigator Email
- rafald@gumed.edu.pl
- Contact Person Name
- Rafał Dziadziuszko
- Contact Person Email
- rafald@gumed.edu.pl
- Site Name
- Krakowski Szpital Specjalistyczny Im. Sw. Jana Pawla II
- Department Name
- Oddział Onkologii z Pododdziałem Diagnostyki Nowotworów Klatki Piersiowej
- Principal Investigator Name
- Grzegorz Czyżewicz
- Principal Investigator Email
- g.czyzewicz@szpitaljp2.krakow.pl
- Contact Person Name
- Grzegorz Czyżewicz
- Contact Person Email
- g.czyzewicz@szpitaljp2.krakow.pl
Italy
- Earliest CTIS Part Ii Submission Date
- 21-05-2024
- Latest Decision Or Authorization Date
- 03-06-2024
- Processing Time Days
- 13
- Number Of Sites
- 3
- Number Of Participants
- 20
Sites
- Site Name
- Azienda Ospedaliero-Universitaria San Luigi Gonzaga
- Department Name
- Thoracic Oncology
- Principal Investigator Name
- Silvia Novello
- Principal Investigator Email
- silvia.novello@unito.it
- Contact Person Name
- Silvia Novello
- Contact Person Email
- silvia.novello@unito.it
- Site Name
- Fondazione IRCCS Istituto Nazionale Dei Tumori
- Department Name
- Medical Oncology and Hematology
- Principal Investigator Name
- Filippo De Braud
- Principal Investigator Email
- filippo.debraud@istitutotumori.mi.it
- Contact Person Name
- Filippo De Braud
- Contact Person Email
- filippo.debraud@istitutotumori.mi.it
- Site Name
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Department Name
- Clinical Trials Center
- Principal Investigator Name
- Gennaro Daniele
- Principal Investigator Email
- gennaro.daniele@policlinicogemelli.it
- Contact Person Name
- Gennaro Daniele
- Contact Person Email
- gennaro.daniele@policlinicogemelli.it
Belgium
- Earliest CTIS Part Ii Submission Date
- 21-05-2024
- Latest Decision Or Authorization Date
- 03-06-2024
- Processing Time Days
- 13
- Number Of Sites
- 4
- Number Of Participants
- 29
Sites
- Site Name
- Cliniques Universitaires Saint-Luc
- Department Name
- Medical oncology
- Principal Investigator Name
- Rachel Galot
- Principal Investigator Email
- rachel.galot@saintluc.uclouvain.be
- Contact Person Name
- Rachel Galot
- Contact Person Email
- rachel.galot@saintluc.uclouvain.be
- Site Name
- Centre Hospitalier Universitaire Dinant Godinne Sainte-Elisabeth-UCL-Namur
- Department Name
- Oncology
- Principal Investigator Name
- Vincent Vanhaudenarde
- Principal Investigator Email
- vincent.vanhaudenarde@chuuclnamur.uclouvain.be
- Contact Person Name
- Vincent Vanhaudenarde
- Contact Person Email
- vincent.vanhaudenarde@chuuclnamur.uclouvain.be
- Site Name
- Jessa Ziekenhuis
- Department Name
- Oncology
- Principal Investigator Name
- Kristof Cuppens
- Principal Investigator Email
- kristof.cuppens@jessazh.be
- Contact Person Name
- Kristof Cuppens
- Contact Person Email
- kristof.cuppens@jessazh.be
- Site Name
- Algemeen Ziekenhuis Delta
- Department Name
- Department of respiratory diseases
- Principal Investigator Name
- Ingel Demedts
- Principal Investigator Email
- ingel.demedts@azdelta.be
- Contact Person Name
- Ingel Demedts
- Contact Person Email
- ingel.demedts@azdelta.be
Spain
- Earliest CTIS Part Ii Submission Date
- 21-05-2024
- Latest Decision Or Authorization Date
- 04-06-2024
- Processing Time Days
- 14
- Number Of Sites
- 6
- Number Of Participants
- 25
Sites
- Site Name
- Hospital Germans Trias I Pujol
- Department Name
- Oncology
- Principal Investigator Name
- Teresa Moran Bueno
- Principal Investigator Email
- mmoran@iconcologia.net
- Contact Person Name
- Teresa Moran Bueno
- Contact Person Email
- mmoran@iconcologia.net
- Site Name
- Hospital General Universitario Gregorio Maranon
- Department Name
- Oncology
- Principal Investigator Name
- Rosa Alvarez Alvarez
- Principal Investigator Email
- rosa.alvarez.al@gmail.com
- Contact Person Name
- Rosa Alvarez Alvarez
- Contact Person Email
- rosa.alvarez.al@gmail.com
- Site Name
- Hospital Clinico Universitario De Valencia
- Department Name
- Oncology
- Principal Investigator Name
- Amelia Insa Molla
- Principal Investigator Email
- insa_ame@gva.es
- Contact Person Name
- Amelia Insa Molla
- Contact Person Email
- insa_ame@gva.es
- Site Name
- Hospital Universitario 12 De Octubre
- Department Name
- Oncology
- Principal Investigator Name
- Luis Paz-Ares Rodriguez
- Principal Investigator Email
- lpaz.hdoc@salud.madrid.org
- Contact Person Name
- Luis Paz-Ares Rodriguez
- Contact Person Email
- lpaz.hdoc@salud.madrid.org
- Site Name
- Hospital Universitari Vall D Hebron
- Department Name
- Oncology
- Principal Investigator Name
- Enriqueta Felip Font
- Principal Investigator Email
- efelip@vhio.net
- Contact Person Name
- Enriqueta Felip Font
- Contact Person Email
- efelip@vhio.net
- Site Name
- University Hospital Virgen Del Rocio S.L.
- Department Name
- Oncology
- Principal Investigator Name
- Reyes Bernabe Caro
- Principal Investigator Email
- bernabeensayos@gmail.com
- Contact Person Name
- Reyes Bernabe Caro
- Contact Person Email
- bernabeensayos@gmail.com
Netherlands
- Earliest CTIS Part Ii Submission Date
- 21-05-2024
- Latest Decision Or Authorization Date
- 27-05-2024
- Processing Time Days
- 6
- Number Of Sites
- 2
- Number Of Participants
- 30
Sites
- Site Name
- Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
- Department Name
- pulmonary oncology
- Principal Investigator Name
- Willemijn Theelen
- Principal Investigator Email
- w.theelen@nki.nl
- Contact Person Name
- Willemijn Theelen
- Contact Person Email
- w.theelen@nki.nl
- Site Name
- Radboud universitair medisch centrum / RADBOUDUMC
- Department Name
- pulmonary diseases
- Principal Investigator Name
- Chantal Smits-van der Graaf
- Principal Investigator Email
- Chantal.Smits-vanderGraaf@radboudumc.nl
- Contact Person Name
- Chantal Smits-van der Graaf
- Contact Person Email
- Chantal.Smits-vanderGraaf@radboudumc.nl
Sponsor
Primary sponsor
- Full Name
- F. Hoffmann-La Roche AG
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- Switzerland
Contract research organisations
- Name
- IQVIA Limited
- Responsibilities
- Monitoring
- Name
- Pharmaceutical Product Development LLC
- Responsibilities
- sponsorDuties codes: 4 (as listed)
- Name
- Labcorp Early Development Laboratories Inc.
- Responsibilities
- sponsorDuties codes: 4 (laboratory services/bioanalytical)
- Name
- Almac Clinical Technologies LLC
- Responsibilities
- sponsorDuties codes: 3
Third parties
- {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
- {"country":"Belgium","full_name":"CellCarta","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"Labcorp Early Development Laboratories Inc.","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"sponsorDuties codes: 3","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Foundation Medicine Inc.","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
- {"country":"France","full_name":"Median Technologies","duties_or_roles":"sponsorDuties: 15 (Imaging)","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
- {"country":"Canada","full_name":"Axon Communications Inc.","duties_or_roles":"sponsorDuties: 15 (Meeting Organizer)","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"sponsorDuties: 15 (Monitoring)","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- RO 743-5846/F04; RO 743-5846/F07; RO 743-5846/F06
- Active Substance
- DIVARASIB
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- ORAL
- Authorisation Status
- Investigational
- Investigational Product Name
- KEYTRUDA 25 mg/mL concentrate for solution for infusion
- Active Substance
- PEMBROLIZUMAB
- Modality
- Monoclonal antibody
- Routes Of Administration
- INTRAVENOUS INFUSION
- Route
- INTRAVENOUS INFUSION
- Authorisation Status
- Authorised
- Investigational Product Name
- Pemetrexed (multiple marketed presentations)
- Active Substance
- PEMETREXED
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS INFUSION
- Route
- INTRAVENOUS INFUSION
- Authorisation Status
- Authorised
- Investigational Product Name
- Carboplatin (multiple marketed presentations)
- Active Substance
- CARBOPLATIN
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS INFUSION
- Route
- INTRAVENOUS INFUSION
- Authorisation Status
- Authorised
- Investigational Product Name
- Cisplatin (multiple marketed presentations)
- Active Substance
- CISPLATIN
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS INFUSION
- Route
- INTRAVENOUS INFUSION
- Authorisation Status
- Authorised
- Combination Treatment
- Yes
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