Dose-Esc/Exp RMC4630 & Cobi in Relapsed/Refractory Solid Tumors & RMC4630& Osi in EGFR+ Locally Adv/Meta NSCLC

Browse trials for

• Noonan Syndrome 40
• Urinary Bladder Neoplasms 1,649
• Carcinoma, Non-Small-Cell Lung 6,641
• Neoplasms, Squamous Cell 136
• Carcinoma, Squamous Cell 1,779
• Bronchial Neoplasms 46

Keywords

• SHP2
• PTPN11
• NSCLC
• KRAS G12
• BRAF Class 3
• NF1 LOF
• KRAS amplification
• KRAS mutations
• advanced solid tumor
• advanced solid malignancies
• bladder cancer
• carcinoma, non-small-cell lung
• neoplasm, squamous cell
• carcinoma, squamous cell
• esophageal neoplasms carcinoma, bronchogenic
• bronchial neoplasms
• lung neoplasms
• respiratory tract neoplasms
• thoracic neoplasms
• neoplasms by site
• neoplasms
• lung diseases
• respiratory tract diseases
• gastrointestinal cancer
• colorectal cancer
• skin cancer
• ovarian cancer
• pancreatic cancer
• endometrium/uterus cancer
• cervical cancer

Noonan Syndrome

40 studies on the registry are indexed under Noonan Syndrome; 19 are open to participants now.

This study's enrollment of 113 is above the median of 52 across 24 interventional studies indexed under Noonan Syndrome.

Lead sponsor

Revolution Medicines, Inc. is the lead sponsor of 20 studies on the registry; 13 are open to participants now.

Study arms

• Experimental
  RMC-4630 and Cobimetinib

  RMC-4630 and Cobimetinib for oral administration

  Drug: RMC-4630 · Drug: Cobimetinib

• Experimental
  RMC-4630 and Osimertinib

  RMC-4630 and Osimertinib for oral administration

  Drug: RMC-4630 · Drug: Drug: Osimertinib

Interventions

• DrugRMC-4630

  RMC-4630 for oral administration

• DrugCobimetinib

  Cobimetinib for oral administration

  Also known as: GDC-0973, XL518

• DrugDrug: Osimertinib

  Osimertinib for oral administration

  Also known as: Tagrisso, AZD9291

Primary outcomes

1. Number of Participants With Adverse Events (AEs).

   An adverse event (AE) was defined as any untoward medical occurrence in a participant, temporally associated with the use of a pharmaceutical / an investigational product, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product(s) was also an AE. All AEs and SAEs will be collected from the start of intervention until the safety visit or EOT visit, whichever is later. The number of safety-evaluable participants who experienced at least one treatment-emergent AE was reported per protocol.

   Time frame: AEs were collected from the start of intervention through 30 days post last day of study drug taken. Participants were monitored/assessed for adverse events for a maximum of 17 months which includes a maximum duration of 16 months on treatment.

2. Number of Participants With Dose Limiting Toxicities (DLTs)

   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.

   Time frame: Cycle 1: Study Day 1 - Study Day 28 (28 days)

Secondary outcomes

1. Cmax

   Peak plasma concentration of RMC-4630 and cobimetinib or RMC-4630 and osimertinib

   Time frame: 0, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle1 Day 1 and Cycle 1 Day 15

2. Tmax

   Time to achieve peak plasma concentration of RMC-4630 and cobimetinib or RMC-4630 and osimertinib

   Time frame: 0, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle1 Day 1 and Cycle 1 Day 15

3. Area Under the Curve (AUC)

   Area under the plasma concentration time curve of RMC-4630 and cobimetinib or RMC-4630 and osimertinib

   Time frame: 0, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle1 Day 1 and Cycle 1 Day 15

4. Accumulation Ratio

   AUC ratio (C1D15 versus C1D1) of RMC-4630 and cobimetinib or RMC-4630 and osimertinib

   Time frame: 0, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle1 Day 1 and Cycle 1 Day 15

5. Duration of Response (DOR)

   Duration of response of RMC-4630 and cobimetinib or RMC-4630 and osimertinib per RECIST v1.1

   Time frame: Response assessment occurs from the start of intervention until the date of documented disease progression per RECIST 1.1 or the date of subsequent therapy, whichever occurs first.

6. t1/2

   Elimination half-life of RMC-4630 and cobimetinib or RMC-4630 and osimertinib

   Time frame: 0, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle1 Day 1 and Cycle 1 Day 15

7. Overall Response Rate (ORR)

   ORR is defined as the proportion of participants who achieve a CR or PR per RECIST v1.1. ORR and the corresponding 95% two-sided confidence interval were derived.

   Time frame: Response assessment occurs from the start of intervention until the date of documented disease progression per RECIST 1.1 or the date of subsequent therapy, whichever occurs first.

Baseline characteristics

Study documents

• Protocol and statistical analysis plan · Nov 20, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No