Solid TumorsPhase 1NCT03634982
Dose Escalation of RMC-4630 Monotherapy in Relapsed/Refractory Solid Tumors
A Phase 1 study testing RMC-4630 in people with Solid Tumors, run by Revolution Medicines, Inc. at 12 sites in United States.
Trial summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of escalating doses of RMC-4630 monotherapy in adult participants with relapsed/refractory solid tumors and to identify the recommended Phase 2 dose (RP2D). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors
- What is being tested?
- RMC-4630
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 133 participants
- Where
- 12 sitesUnited States
- Study dates
- 28 Sep 2018to 31 May 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant (male or female) ≥18 years of age
- Participants who have advanced solid tumors that have failed, are intolerant to, or are considered ineligible for standard of care anticancer treatments including approved drugs for oncogenic drivers in their tumor type
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- Participants in the Dose-Expansion Component must have one of the following genotypic aberrations: KRAS amplifications, KRASG12C (NSCLC), BRAF Class 3, or NF1 LOF (NSCLC and gynecological cancers) mutations
- Adequate hematologic, hepatic and renal function
- Participant able to understand and voluntarily sign the informed consent form (ICF) and able to comply with the study visit schedule and other protocol requirements.
- Participants willing to agree to not father a child/become pregnant and comply with effective contraception criteria
Who cannot join
- Known or suspected leptomeningeal or brain metastases or spinal cord compression
- Primary central nervous system (CNS) tumors
- 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
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- 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
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
University of Colorado Cancer Center
Aurora, Colorado, 80045
University of Texas at Austin - Dell Medical School
Austin, Texas, 78712
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
City of Hope
Duarte, California, 91010
Sarah Cannon Research Institute - Tennessee Oncology, PLLC
Nashville, Tennessee, 37203
University of Oklahoma - Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
UC Irvine - Chao Family Comprehensive Cancer Center
Orange, California, 92868
UC Davis Comprehensive Cancer Center
Sacramento, California, 95817
UC San Francisco - Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94115
Sarah Cannon Research Institute - Florida Cancer Specialists
Sarasota, Florida, 34232
Honor Health Research Institute
Scottsdale, Arizona, 85258
Moffit Cancer Center
Tampa, Florida, 33612
About this study
Official title: A Phase 1, Open-Label, Multicenter, Dose-Escalation Study of RMC-4630 Monotherapy in Adult Participants With Relapsed/Refractory Solid Tumors
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of escalating doses of RMC-4630 monotherapy in adult participants with relapsed/refractory solid tumors and to identify the recommended Phase 2 dose (RP2D).
Read the detailed description
This is an open-label, multicenter, Phase 1 study of oral RMC-4630 monotherapy in participants with advanced relapsed or refractory solid tumors. The study will include 2 components: 1) a Dose-Escalation Component for participants with relapsed or refractory solid tumors and 2) a Dose-Expansion Component for participants with relapsed or refractory solid tumors harboring certain specific mutations/rearrangements that result in hyperactivation of the RAS-MAPK pathway. Participants will be treated until disease progression per RECIST v1.1, unacceptable toxicity, or other criteria for withdrawal are met, whichever occurs first.
- Conditions
- Solid Tumors
- Being tested
- RMC-4630
- Keywords
- SHP2, PTPN11, NSCLC, EGFR, KRAS G12, BRAF Class 3, NF1 LOF, advanced solid tumor, advanced solid malignancies, melanoma, skin cancer, ovarian cancer, endometrium/uterus cancer, bladder cancer, cervical cancer, Carcinoma, Non-Small-Cell Lung, Neoplasms, Squamous Cell, Carcinoma, Squamous Cell, Esophageal Neoplasms, Carcinoma, Bronchogenic
- Medical subject headings
- Noonan Syndrome, Melanoma, Skin Neoplasms, Ovarian Neoplasms, Uterine Neoplasms, Urinary Bladder Neoplasms, Uterine Cervical Neoplasms, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RMC-4630Drug
RMC-4630 for oral administration
| Study group | Role | What they receive |
|---|---|---|
| RMC-4630 | Experimental | RMC-4630 for oral administration Receives: Drug: RMC-4630 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with adverse events (AEs)
Incidence, nature, and severity of treatment-emergent AEs and serious AEs, including incidence and severity of findings in laboratory values and vital signs for RMC-4630 monotherapy
Measured: up to 3 years
Number of participants with dose limiting toxicities (DLTs)
Incidence and nature of DLTs with RMC-4630 monotherapy
Measured: 28 days
Secondary outcomes (7)
Cmax
Peak plasma concentration of RMC-4630
Measured: up to 3 years
Tmax
Time to achieve peak plasma concentration of RMC-4630
Measured: up to 3 years
Area Under the Curve (AUC)
Area under the plasma concentration time curve of RMC-4630
Measured: up to 3 years
t1/2
Elimination half-life of RMC-4630
Measured: up to 3 years
Accumulation Ratio
Ratio of accumulation of RMC-4630 from a single dose to steady state with repeated dosing
Measured: up to 3 years
Overall Response Rate (ORR)
Overall response rate of RMC-4630 per RECIST v1.1
Measured: up to 3 years
Duration of Response (DOR)
Duration of response of RMC-4630 per RECIST v1.1
Measured: up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2018
- Study start28 Sep 2018
- Primary completion31 Mar 2023 (estimated)
- Study completion31 May 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- More trials run by Revolution Medicines, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 133 participants (actual)
Sponsor and investigators
- Lead sponsor
- Revolution Medicines, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Sanofi
- Responsible party
- Sponsor
- Investigators
- Revolution Medicines, Inc., Study director, Revolution Medicines, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03634982
- Sponsor's protocol ID
- RMC-4630-01
- Status last verified
- Sep 2021
- First submitted
- 10 Aug 2018
- Last updated
- 1 Sep 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label, Multicenter, Dose-Escalation Study of RMC-4630 Monotherapy in Adult Participants With Relapsed/Refractory Solid Tumors
- ClinicalTrials.gov ID
- NCT03634982
- Acronym / sponsor ID
- RMC-4630-01
- Conditions
- Solid Tumors
- Keywords
- SHP2, PTPN11, NSCLC, EGFR, KRAS G12, BRAF Class 3, NF1 LOF, advanced solid tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 133 participants (actual)
- Lead sponsor
- Revolution Medicines, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Sanofi
- Study start
- 28 Sep 2018 (actual)
- Primary completion
- 31 Mar 2023 (estimated)
- Study completion
- 31 May 2023 (estimated)
- First posted
- 17 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of escalating doses of RMC-4630 monotherapy in adult participants with relapsed/refractory solid tumors and to identify the recommended Phase 2 dose (RP2D).
Detailed description
This is an open-label, multicenter, Phase 1 study of oral RMC-4630 monotherapy in participants with advanced relapsed or refractory solid tumors. The study will include 2 components: 1) a Dose-Escalation Component for participants with relapsed or refractory solid tumors and 2) a Dose-Expansion Component for participants with relapsed or refractory solid tumors harboring certain specific mutations/rearrangements that result in hyperactivation of the RAS-MAPK pathway. Participants will be treated until disease progression per RECIST v1.1, unacceptable toxicity, or other criteria for withdrawal are met, whichever occurs first.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RMC-4630 | Experimental | Drug: RMC-4630RMC-4630 for oral administration |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Participant (male or female) ≥18 years of age
- Participants who have advanced solid tumors that have failed, are intolerant to, or are considered ineligible for standard of care anticancer treatments including approved drugs for oncogenic drivers in their tumor type
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- Participants in the Dose-Expansion Component must have one of the following genotypic aberrations: KRAS amplifications, KRASG12C (NSCLC), BRAF Class 3, or NF1 LOF (NSCLC and gynecological cancers) mutations
- Adequate hematologic, hepatic and renal function
Key exclusion criteria (9 listed)
- Known or suspected leptomeningeal or brain metastases or spinal cord compression
- Primary central nervous system (CNS) tumors
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RMC-4630RMC-4630 for oral administration | Drug | RMC-4630 |
Primary outcome
Number of participants with adverse events (AEs)
Time frame: up to 3 years
Incidence, nature, and severity of treatment-emergent AEs and serious AEs, including incidence and severity of findings in laboratory values and vital signs for RMC-4630 monotherapy
Number of participants with dose limiting toxicities (DLTs)
Time frame: 28 days
Incidence and nature of DLTs with RMC-4630 monotherapy
7 secondary outcomes
Cmax
Time frame: up to 3 years
Tmax
Time frame: up to 3 years
Area Under the Curve (AUC)
Time frame: up to 3 years
t1/2
Time frame: up to 3 years
Accumulation Ratio
Time frame: up to 3 years
Overall Response Rate (ORR)
Time frame: up to 3 years
Duration of Response (DOR)
Time frame: up to 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Revolution Medicines, Inc. study director
Revolution Medicines, Inc.
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RMC-4630 in people with Solid Tumors, run by Revolution Medicines, Inc. at 12 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with adverse events (AEs) (time frame: up to 3 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2022.