{"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"1"},{"groupId":"OG001","value":"0"},{"groupId":"OG002","value":"3"},{"groupId":"OG003","value":"1"},{"groupId":"OG004","value":"0"},{"groupId":"OG005","value":"2"},{"groupId":"OG006","value":"1"},{"groupId":"OG007","value":"2"}]}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"6"},{"groupId":"OG001","value":"6"},{"groupId":"OG002","value":"9"},{"groupId":"OG003","value":"6"},{"groupId":"OG004","value":"5"},{"groupId":"OG005","value":"6"},{"groupId":"OG006","value":"4"},{"groupId":"OG007","value":"4"}],"units":"Participants"}],"description":"Any toxicities occurring during the DLT observation period (cycle 1) that were considered R/T study treatment, including GR4 AEs; GR3 febrile neutropenia or hemorrhage; GR3 thrombocytopenia with clinically significant bleeding; GR ≥2 pneumonitis; GR3 hypertension or rash which does not improve or remains uncontrolled for \\>5 or more days despite maximal supportive care; GR3 non hematologic AEs that remain uncontrolled for \\>72 hours despite maximal supportive care; Concurrent elevation of AST or ALT \\>3 × ULN \\& total bilirubin \\>2 × ULN or international normalized ratio (INR) \\>1.5 in the absence of cholestasis and other causes; Grade 3 QTcF prolongation based on a triplicate ECG; Ejection fraction \\<50% with an absolute decrease of \\>10% from baseline; Retinal vein occlusion any grade; 50% or less dose intensity of RMC4630 and/or cobimetnib or osimertinib due to study drug related toxicity. Refer to protocol for further details.","groups":[{"description":"Participants who received intermittent dose of RMC-4630 80 mg or 140 mg on D1 and D4 or on D1 and D2 of a 28-day cycle and daily dose of Cobimetinib 20 mg or 40 mg from D1 through D21 and then 7 days off Cobimetinib from D22 to D28 of a 28-day cycle.","id":"OG000","title":"Intermittent RMC-4630 (D1D4 or D1D2) + Daily Cobimetinib (QD21/7)"},{"description":"Participants who received intermittent dose of RMC-4630 140 mg on D1 and D2 of a 28-day cycle and intermittent dose of Cobimetinib 40 mg or 60 mg on D1 and D2 of a 28-day cycle.","id":"OG001","title":"Intermittent RMC-4630 (D1D2) + Intermittent Cobimetinib (D1D2)"},{"description":"Participants who received intermittent dose of RMC-4630 140 mg on D1 and D4 of a 28-day cycle and Cobimetinib 20mg QD 21days on and 7 days off of a 28-day cycle.","id":"OG002","title":"Intermittent RMC-4630 140mg (D1D4) + Cobimetinib 20mg QD (21/7)"},{"description":"Participants who received intermittent dose of RMC-4630 140 mg on D1 and D2 of a 28-day cycle and Cobimetinib 20mg QD 21days on and 7 days off of a 28-day cycle.","id":"OG003","title":"Intermittent RMC-4630 140mg (D1D2) + Cobimetinib 20mg QD (21/7)"},{"description":"Participants who received intermittent dose of RMC-4630 140 mg on D1 and D2 of a 28-day cycle and Cobimetinib 40mg D1 and D2 of a 28-day cycle.","id":"OG004","title":"Intermittent RMC-4630 140mg (D1D2) + Cobimetinib 40mg (D1D2)"},{"description":"Participants who received intermittent dose of RMC-4630 140 mg on D1 and D2 of a 28-day cycle and Cobimetinib 60mg D1 and D2 of a 28-day cycle.","id":"OG005","title":"Intermittent RMC-4630 140mg (D1D2) + Cobimetinib 60mg D1D2"},{"description":"Participants who received intermittent dose of RMC-4630 100 mg on D1 and D2 of a 28-day cycle and daily dose of Osimertinib 80 mg from D1 through D28 of a 28-day cycle.","id":"OG006","title":"Intermittent RMC-4630 100mg (D1D2) + Osimertinib 80mg (QD)"},{"description":"Participants who received intermittent dose of RMC-4630 140 mg on D1 and D2 of a 28-day cycle and daily dose of Osimertinib 80 mg from D1 through D28 of a 28-day cycle.","id":"OG007","title":"Intermittent RMC-4630 140mg (D1D2) + Osimertinib 80mg (QD)"}],"paramType":"COUNT_OF_PARTICIPANTS","populationDescription":"DLT-evaluable population was defined as the following: All treated participants in the dose escalation phase who completed the DLT period and received at least 75% of planned dose of RMC-4630 and cobimetinib or RMC-4630 and Osimertinib (ie, not have missed ≥3 doses of RMC-4630 and cobimetinib on the D1D2 intermittent schedule or ≥6 doses of cobimetinib on the 21 on/7 off schedule, or ≥8 doses for reasons other than toxicity) within the DLT observation period (i.e Cycle 1)","reportingStatus":"POSTED","timeFrame":"Cycle 1: Study Day 1 - Study Day 28 (28 days)","title":"Number of Participants With Dose Limiting Toxicities (DLTs)","type":"PRIMARY","unitOfMeasure":"Participants"}