NCT03989115 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1, PHASE2
Status at capture: COMPLETED
Registry last update: 2023-06-26

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) proﬁles of RMC-4630 and cobimetinib in adult participants with relapsed/refractory solid tumors with specific genomic aberrations and to identify the recommended Phase 2 dose (RP2D); and to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) proﬁles of RMC-4630 and osimertinib in adult participants with EGFR mutation-positive locally advanced or metastatic NSCLC.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Number of Participants With Adverse Events (AEs).

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outcome · POSTED

Number of Participants With Dose Limiting Toxicities (DLTs)

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outcome · POSTED

Cmax

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outcome · POSTED

Tmax

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outcome · POSTED

Area Under the Curve (AUC)

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outcome · POSTED

Accumulation Ratio

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outcome · POSTED

Duration of Response (DOR)

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outcome · POSTED

t1/2

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outcome · POSTED

Overall Response Rate (ORR)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Age ≥18 years * For RMC-4630 + Cobimetinib only - Participants who have advanced solid tumors that have failed, are intolerant to, or are considered ineligible for standard of care anti-cancer treatments including approved drugs for oncogenic drivers in their tumor type. * For RMC-4630 + Osimertinib only - Locally advanced or metastatic EGFR mutant NSCLC not amenable to curative surgery or radiotherapy * For RMC-4630 + Cobimetinib only - Participants must have one of the following genotypic aberrations: KRAS mutations and amplifications, BRAF Class 3 mutations, or NF1 LOF mutations * For RMC-4630 + Osimertinib only - Evidence of radiological documentation of progression with osimertinib monotherapy or an osimertinib containing regimen. Participants should not be considered a current candidate for 1st generation EGFR TKI's by the investigator. * Eastern Cooperative Oncology Group (ECOG) performance status of ≤1 * Adequate hematological, hepatic, and renal function * Capable of giving signed informed consent form (ICF). Willing and able to compile with study requirements and restrictions * Life expectancy \>12 weeks * Female of childbearing potential and males with partners of childbearing potential must comply with effective contraception criteria . Exclusion Criteria: * Primary central nervous system (CNS) tumors. * Known or suspected leptomeningeal or brain metastases or spinal cord compression. * For RMC-4630 + osimertinib arm only - Known or suspected Small cell, squamous, or pleomorphic lung transformations * Clinically significant cardiac disease * Active, clinically signiﬁcant interstitial lung disease or pneumonitis * History or current evidence of retinal pigment epithelial detachment (RPED), central serous retinopathy, retinal vein occlusion (RVO), or predisposing factors to RPED or RVO * Known HIV infection or active/chronic hepatitis B or C infection. * Any other unstable or clinically signiﬁcant concurrent medical condition that would, in the opinion of the investigator, jeopardize the safety of a participant, impact their expected survival through the end of the study participation, and/or impact their ability to comply with the protocol prior/concomitant therapy * Females who are pregnant or breastfeeding
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
RMC-4630 and Cobimetinib for oral administration
intervention Names
Drug: RMC-4630
Drug: Cobimetinib
label
RMC-4630 and Cobimetinib
type
EXPERIMENTAL
description
RMC-4630 and Osimertinib for oral administration
intervention Names
Drug: RMC-4630
Drug: Drug: Osimertinib
label
RMC-4630 and Osimertinib
type
EXPERIMENTAL

interventions

arm Group Labels
RMC-4630 and Cobimetinib
RMC-4630 and Osimertinib
description
RMC-4630 for oral administration
name
RMC-4630
type
DRUG
arm Group Labels
RMC-4630 and Cobimetinib
description
Cobimetinib for oral administration
name
Cobimetinib
other Names
GDC-0973, XL518
type
DRUG
arm Group Labels
RMC-4630 and Osimertinib
description
Osimertinib for oral administration
name
Drug: Osimertinib
other Names
Tagrisso
AZD9291
type
DRUG

Study design

allocation

NON_RANDOMIZED

intervention Model

PARALLEL

intervention Model Description

This is a dose escalation study followed by dose expansion.

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 113
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Number of Participants With Adverse Events (AEs).
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.
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.
measure
Number of Participants With Dose Limiting Toxicities (DLTs)
time Frame
Cycle 1: Study Day 1 - Study Day 28 (28 days)

secondary Outcomes

description
Peak plasma concentration of RMC-4630 and cobimetinib or RMC-4630 and osimertinib
measure
Cmax
time Frame
0, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle1 Day 1 and Cycle 1 Day 15
description
Time to achieve peak plasma concentration of RMC-4630 and cobimetinib or RMC-4630 and osimertinib
measure
Tmax
time Frame
0, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle1 Day 1 and Cycle 1 Day 15
description
Area under the plasma concentration time curve of RMC-4630 and cobimetinib or RMC-4630 and osimertinib
measure
Area Under the Curve (AUC)
time Frame
0, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle1 Day 1 and Cycle 1 Day 15
description
AUC ratio (C1D15 versus C1D1) of RMC-4630 and cobimetinib or RMC-4630 and osimertinib
measure
Accumulation Ratio
time Frame
0, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle1 Day 1 and Cycle 1 Day 15
description
Duration of response of RMC-4630 and cobimetinib or RMC-4630 and osimertinib per RECIST v1.1
measure
Duration of Response (DOR)
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.
description
Elimination half-life of RMC-4630 and cobimetinib or RMC-4630 and osimertinib
measure
t1/2
time Frame
0, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle1 Day 1 and Cycle 1 Day 15
description
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.
measure
Overall Response Rate (ORR)
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.

Full study description

brief Summary: The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) proﬁles of RMC-4630 and cobimetinib in adult participants with relapsed/refractory solid tumors with specific genomic aberrations and to identify the recommended Phase 2 dose (RP2D); and to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) proﬁles of RMC-4630 and osimertinib in adult participants with EGFR mutation-positive locally advanced or metastatic NSCLC.
detailed Description: This open-label, phase 1b/2 dose-escalation and dose-expansion study is designed to evaluate the safety and maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of RMC-4630 in combination with cobimetinib in participants with relapsed/refractory solid tumors; and of RMC-4630 in combination with osimertinib in adult participants with EGFR mutation-positive locally advanced or metastatic NSCLC.

Source references

Source notices and limitations

Discovery and provenance

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Preserved source evidence · Not medical advice