A clinical study to investigate the safety and activity of Divarasib at different doses in combination with other cancer therapies in patients with non-small cell lung cancer (NSCLC) that has a KRAS G12C mutation and has spread, and who have not been treated for it before.
Descrizione riassuntiva dello studio
This clinical study includes patients who have not been previously treated for locally advanced or metastatic NSCLC. Additionally, the NSCLC must have a KRAS-G12C mutation. The aim of this clinical study is to test the safety and activity of Divarasib at different doses in combination with other cancer therapies and to understand how the body processes these medications. Participants will receive the clinical study treatment Divarasib in combination either with Pembrolizumab (Cohort A1, A2) or with Pembrolizumab and two chemotherapeutics (Cohort B), with the platinum-based chemotherapeutic agent being stopped after four infusions. They will receive the study treatment in 21-day treatment sections (called “treatment cycles”) until their investigator determines that they are no longer benefiting from the treatment or if they have unacceptable side effects. Participants will see the investigator during the first two treatment cycles every week, then every two weeks during cycles 3 and 4, and then every three weeks during the remaining treatment cycles. During these hospital visits, it will also be checked how the participant responds to the treatment and whether side effects occur. How long participants will be involved in the clinical study overall depends on how their NSCLC responds to the treatment. It can take a day or longer than 2 years. After the administration of the last dose of the clinical study treatment, the investigator will examine the participants every three months as long as they agree. Participants can discontinue the study treatment at any time and withdraw from the clinical study.
(BASEC)
Intervento studiato
Individuals are screened to determine if they can participate in the study. The pre-screening period occurs approximately one month before the start of treatment. Each participant in this clinical study will be assigned to one of three groups (A1, A2, or B), depending on when they started the study and whether their NSCLC is PD-L1 positive. Each will receive Divarasib as a tablet to be taken once daily, as well as Pembrolizumab as an intravenous infusion every 3 weeks. Group B will also receive a platinum-based chemotherapy and Pemetrexed as an intravenous infusion every 3 weeks, and after the first 4 infusions, the platinum agent will be stopped. Participants may receive Divarasib with the standard dose of the other cancer therapies. Participants in Group A1 may participate in 1 of 2 sections of the study, depending on when they join the study. Small groups of individuals joining the second section will receive different doses of Divarasib. The likelihood of being assigned to one of the dose groups is equal. This is an open-label study. This means that all parties involved, including participants and the investigator, will know which study treatment the participant has received. During this study, participants will visit the investigator every week for the first 6 weeks, 4 times in the next 6 weeks, and then every 3 weeks. The investigator will assess how well the treatment works and whether any adverse effects have occurred in the participants. Participants will have follow-up appointments 1 month after the completion of the study treatment, and then visit appointments or phone calls every 3 months or as long as the participant agrees. The investigator will check the participant's well-being during the follow-up appointments or phone calls. Overall participation in the study lasts about 2 years. Participants have the right to discontinue the study treatment at any time and withdraw from the study if they wish.
(BASEC)
Malattie studiate
This clinical study includes patients with locally advanced or metastatic NSCLC who have not been previously treated. Additionally, the NSCLC must have a KRAS-G12C mutation. Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. New therapies are needed to improve treatment outcomes for people with locally advanced or metastatic NSCLC. “Locally advanced” means that the NSCLC has spread to surrounding tissue, and “metastatic” means that it has spread to other parts of the body. The standard first-line treatment for locally advanced or metastatic NSCLC includes medications that help the body's immune system attack the tumor (called “immunotherapy”), such as Pembrolizumab, which is given with or without chemotherapy. Treatment with Pembrolizumab is more successful when cancer cells express the PD-L1 protein. About 1 in 10 people with NSCLC have a specific alteration (mutation) in the KRAS gene of the cancer cells, referred to as the KRAS G12C mutation. This leads to uncontrolled growth of the cancer cells. Recent studies have shown that NSCLC cells with a KRAS G12C mutation are often also PD-L1 positive. Divarasib is an experimental drug. This means that it is not approved for the treatment of NSCLC. In this clinical study, researchers will investigate how safe and effective Divarasib is against NSCLC that has a KRAS-G12C mutation when administered in combination with cancer therapies.
(BASEC)
Individuals who can participate in this study must be at least 18 years old and have NSCLC that has spread and has a KRAS G12C mutation. (BASEC)
Criteri di esclusione
Participation in this study may be excluded if any of the following applies to the patient: • Your NSCLC can be surgically removed • You have already been treated for NSCLC that has spread, or you have previously received certain treatments, including KRAS G12C drugs • Your NSCLC has spread to the brain or spinal cord, is untreated or causing symptoms, or you have been treated with certain medications • You have certain other conditions such as heart problems or hepatitis virus infections • You are pregnant or breastfeeding. (BASEC)
Luogo dello studio
Basilea, Berna
(BASEC)
Sponsor
na
(BASEC)
Contatto per ulteriori informazioni sullo studio
Persona di contatto in Svizzera
Clinical Trials
+41 61 715 44 85
switzerland.clinical-research@clutterroche.comRoche Pharma (Schweiz) AG
(BASEC)
Informazioni generali
F. Hoffmann-La Roche Ltd
switzerland.clinical-research@clutterroche.com(ICTRP)
Informazioni scientifiche
F. Hoffmann-La Roche Ltd
switzerland.clinical-research@clutterroche.com(ICTRP)
Nome del comitato etico approvante (per studi multicentrici solo il comitato principale)
Commissione d'etica svizzera nord-ovest/centrale EKNZ
(BASEC)
Data di approvazione del comitato etico
21.09.2023
(BASEC)
ID di studio ICTRP
EUCTR2022-003048-28 (ICTRP)
Titolo ufficiale (approvato dal comitato etico)
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 CANC (BASEC)
Titolo accademico
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 (ICTRP)
Titolo pubblico
A 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 (ICTRP)
Malattie studiate
Untreated Advanced or Metastatic Non-Small Cell Lung Cancer
MedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.1Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps);Therapeutic area: Diseases [C] - Cancer [C04] (ICTRP)
Intervento studiato
Product Name: GDC-6036
Product Code: RO7435846
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: GDC-6036
Current Sponsor code: Ro 743-5846/F07
Other descriptive name: 1-((S)-4-((R)-7-(6-amino-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-6-chloro-8-fluoro-2-(((S)-1-methylpyrrolidin-2-yl)methoxy)quinazolin-4-yl)-3-methylpiperazin-1-yl)prop-2-en-1-one
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Product Name: GDC-6036
Product Code: RO7435846
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: GDC-6036
Current Sponsor code: Ro 743-5846/F04
Other descriptive name: 1-((S)-4-((R)-7-(6-amino-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-6-chloro-8-fluoro-2-(((S)-1-methylpyrrolidin-2-yl)methoxy)quinazolin-4-yl)-3-methylpiperazin-1-yl)prop-2-en-1-one
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Product Name: GDC-6036
Product Code: RO7435846
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: GDC-6036
Current Sponsor code: Ro 743-5846/F06
Other descriptive name: 1-((S)-4-((R)-7-(6-amino-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-6-chloro-8-fluoro-2-(((S)-1-methylpyrrolidin-2-yl)methoxy)quinazolin-4-yl)-3-methylpiperazin-1-yl)prop-2-en-1-one
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Trade Name: Keytruda
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Keytruda
Other descriptive name: Pembrolizumab
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-
Trade Name: Carboplatin
Product Name: Carboplatin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Carboplatin
Current Sponsor code: N/A
Concentration unit: mg/ml milli (ICTRP)
Tipo di studio
Interventional clinical trial of medicinal product (ICTRP)
Disegno dello studio
Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2 (ICTRP)
Criteri di inclusione/esclusione
Gender:
Female: yes
Male: yes
Inclusion criteria:
- Histologically or cytologically documented locally advanced unresectable or metastatic non-squamous NSCLC that is not eligible for curative surgery and/or definitive chemoradiotherapy
- No prior systemic treatment for advanced unresectable or metastatic NSCLC
-Confirmation of Biomarker eligibility:
.. Documented history of the KRAS G12C mutation
.. Documented history of PD-L1 expression
- For Cohort A, PD-L1 tumor cell expression >= 1% is required to
be eligible
- For Cohort B, PD-L1 tumor cell expression is not required to be
eligible
- 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
- Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30
(ICTRP)
Exclusion criteria:
- Known concomitant second oncogenic driver with available targeted treatment
- 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 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
- 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
Endpoint primari e secondari
Main Objective: To evaluate the safety and tolerability of divarasib in combination with pembrolizumab (Cohort A) and divarasib in combination with pembrolizumab plus platinum-based chemotherapy and pemetrexed (Cohort B);Secondary Objective: - To evaluate the activity of divarasib in combination with pembrolizumab (Cohort A) and divarasib in combination with pembrolizumab plus platinum-based chemotherapy and pemetrexed (Cohort B)
- To evaluate the tolerability of divarasib in combination with pembrolizumab (Cohort A) and divarasib in combination with pembrolizumab plus platinum-based chemotherapy and pemetrexed (Cohort B)
- To characterize the divarasib PK profile
- To identify a recommended dose of divarasib in combination regimens with pembrolizumab (Cohort A) and pembrolizumab plus platinum-based
chemotherapy and pemetrexed (Cohort B);Primary end point(s): 1. Occurrence of adverse events
2. Change from baseline at each visit in targeted safety parameters;Timepoint(s) of evaluation of this end point: 1-2. Until 60 days after the final dose of study treatment or until initiation of another anti-cancer therapy, whichever occurs first (ICTRP)
Secondary end point(s): 1. Objective response rate
2. Duration of response
3. Progression free survival
4. 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)
5. Change from baseline in symptomatic side effects, as assessed through use of the PRO-CTCAE
6. Proportion of participants reporting "frequent" or "almost constant" diarrhea during the first three cycles of treatment according to the PRO-CTCAE criteria
7. Proportion of participants reporting "severe" or "very severe" nausea or vomiting during the first three cycles of treatment according to the PRO-CTCAE
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)
9. Plasma concentration of divarasib at specified timepoints
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;Timepoint(s) of evaluation of this end point: 1-8. Up to 2 years
9. 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
10. Up to 2 years
(ICTRP)
Data di registrazione
29.03.2023 (ICTRP)
Inclusione del primo partecipante
01.03.2023 (ICTRP)
Sponsor secondari
non disponibile
Contatti aggiuntivi
Trial Information Support Line-TISL, global.rochegenentechtrials@roche.com, F. Hoffmann-La Roche Ltd (ICTRP)
ID secondari
BO44426 (ICTRP)
Risultati-Dati individuali dei partecipanti
non disponibile
Ulteriori informazioni sullo studio
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2022-003048-28 (ICTRP)
Risultati dello studio
Riepilogo dei risultati
non disponibile
Link ai risultati nel registro primario
non disponibile