Carcinoma, Non-Small-Cell LungPhase 1/2KaRAnaSaNCT07227025
A Study of Amivantamab and Olomorasib Combination Therapy in Participants With Metastatic Non-Small Cell Lung Cancer
A Phase 1/2 study testing Amivantamab and Olomorasib in people with Carcinoma, Non-Small-Cell Lung, run by Janssen Research & Development, LLC at 12 sites in 5 countries.
Trial summary
The main purpose of this study is to find out the most suitable dose (recommended phase 2 combination dose [RP2CD]) of amivantamab and olomorasib combination therapy and to assess how well the combination slows down or prevents the growth of tumors in participants with KRAS G12C mutant metastatic non-small cell lung… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung
- What is being tested?
- Amivantamab and Olomorasib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 12 sitesin 5 countries
- Study dates
- 3 Mar 2026to 30 Apr 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 must have histologically or cytologically confirmed metastatic NSCLC characterized by a KRAS G12C mutation at the time of enrollment. For Phase 1: Participant must have progressed on or after, or have intolerance to, platinum-based chemotherapy and Programmed Death-Ligand 1 (PD-L1)-targeted immunotherapy given in combination or sequentially. Receipt of additional lines of prior therapy is permitted. Progression must have occurred on or after the most recent line of systemic anticancer therapy. For Phase 2: Participant must have progressed on or after platinum-based chemotherapy and PD-L1-targeted immunotherapy given in combination or sequentially. Progression must have occurred on or after the most recent line of systemic anticancer therapy. Receipt of additional lines of prior therapy is not permitted
- Participant must have at least 1 measurable lesion, according to RECIST version.1.1, that has not been previously irradiated
- May have brain metastases only if previously definitively, locally treated, and participant is clinically stable and asymptomatic for greater than (>) 2 weeks and is off or receiving low-dose corticosteroid treatment for at least 2 weeks prior to start of study treatment
- Can have a prior or concurrent second malignancy (other than the disease under study) with natural history or treatment course that is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s)
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Who cannot join
- Participant has history of uncontrolled illness
- Suspected or known allergies, hypersensitivity, or intolerance to amivantamab excipients or olomorasib excipients
- Medical history of (non-infectious) interstitial lung disease (ILD)/pneumonitis, or has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
- Presence of primary driver mutations (epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK], mesenchymal-epithelial transition [MET], human epidermal growth factor receptor 2 [HER2], ROS1, neurotrophic tyrosine receptor kinase [NTRK], B-Raf proto-oncogene [BRAF], rearranged during Transfection [RET], neuroblastoma RAS viral oncogene homolog [NRAS], and other KRAS mutations besides G12C) as determined by local genomic testing
- Prior treatment with any KRAS inhibitor
Trial locations and contacts
12 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
12 sites in 5 countries
China3 sites, 3 recruiting
- Recruiting
The First Affiliated Hospital Sun Yat sen University
Guangzhou, 510060
- Recruiting
Harbin medical university cancer hospital
Harbin, 150000
- Recruiting
Shanghai East Hospital
Shanghai, 310000
South Korea3 sites, 3 recruiting
- Recruiting
Severance Hospital Yonsei University Health System
Seoul, 03722
- Recruiting
Asan Medical Center
Seoul, 05505
- Recruiting
Samsung Medical Center
Seoul, 06351
Turkey (Türkiye)3 sites, 3 recruiting
- Recruiting
Ankara Universitesi Hastaneleri Tibbi Farmakoloji Anabilim Dali Faz 1 Klinik Arastirma Merkezi
Ankara, 06620
- Recruiting
Ankara Bilkent Sehir Hastanesi
Çankaya, 06800
- Recruiting
Koc Universitesi Hastanesi Faz 1 Klinik Arastirma Merkezi
Istanbul, 34010
United States2 sites, 2 recruiting
- Recruiting
Virginia Cancer Specialists
Fairfax, Virginia, 22031
- Recruiting
New York University Langone Medical Center
New York, New York, 10016
Canada1 site, 1 recruiting
- Recruiting
Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
About this study
Official title: A Phase 1/2 Study Evaluating the Safety and Efficacy of Amivantamab and Olomorasib Combination Therapy in Metastatic Non-small Cell Lung Cancer
The main purpose of this study is to find out the most suitable dose (recommended phase 2 combination dose [RP2CD]) of amivantamab and olomorasib combination therapy and to assess how well the combination slows down or prevents the growth of tumors in participants with KRAS G12C mutant metastatic non-small cell lung cancer (NSCLC: the most common type of lung cancer; metastatic: has spread to other parts of the body; KRAS G12C mutant: mutation [change] in the kirsten rat sarcoma viral oncogene homolog [KRAS] gene in tumor cells in which glycine [G] at position 12 is replaced with cystine [C]).
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Being tested
- Amivantamab, Olomorasib
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmivantamabDrug
Also called JNJ-61186372, RYBREVANT
Amivantamab will be administered.
OlomorasibDrug
Also called LY3537982
Olomorasib will be administered.
| Study group | Role | What they receive |
|---|---|---|
| Phase 1: Combination Dose Selection | Experimental | Participants will receive amivantamab along with olomorasib to determine the RP2CD of the combination therapy until disease progression, significant toxicity, or until another criterion for discontinuation of study treatment is met. Eligible participants may have the option to transfer to a long-term extension (LTE) phase for continued access to study treatments. Receives: Drug: Amivantamab; Drug: Olomorasib |
| Phase 2: Expansion | Experimental | Participants will receive amivantamab and olomorasib combination therapy at the RP2CD determined in Phase 1 until disease progression, significant toxicity, or until another criterion for discontinuation of study treatment is met. Eligible participants may have the option to transfer to LTE phase for continued access to study treatments. Receives: Drug: Amivantamab; Drug: Olomorasib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Number of Participants with Adverse Events (AEs) by Severity
An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An assessment of severity grade will be made by the investigator according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 defined as follows: Grade 1 (mild; asymptomatic or mild symptoms; intervention not indicated); Grade 2 (moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living [ADL]); Grade 3 (severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL); Grade 4 (life-threatening consequences; urgent intervention indicated); Grade 5 (Death related to adverse event).
Measured: Up to approximately 3 years 2 months
Phase 1: Number of Participants with Dose-Limiting Toxicities (DLTs)
DLT is defined as drug related adverse events and includes unacceptable non-hematologic toxicity, hematologic toxicity, pulmonary toxicity, or elevations in hepatic enzymes suggestive of drug-induced liver injury of Grade 3 or higher. Toxicities will be graded for severity according to the NCI-CTCAE, version 5.0.
Measured: Up to approximately 3 years 2 months
Phase 2: Confirmed Objective Response Rate (ORR)
ORR is defined as the percentage of participants who achieve either a confirmed partial response (PR) or complete response (CR), using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 by investigator review. Confirmatory analysis may be performed using Blinded Independent Central Review (BICR).
Measured: Up to approximately 3 years 2 months
Secondary outcomes (6)
Number of Participants with Adverse Events (AEs) by Severity
An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An assessment of severity grade will be made by the investigator according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 defined as follows: Grade 1 (mild; asymptomatic or mild symptoms; intervention not indicated); Grade 2 (moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living [ADL]); Grade 3 (severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL); Grade 4 (life-threatening consequences; urgent intervention indicated); Grade 5 (Death related to adverse event).
Measured: Up to approximately 3 years 2 months
Number of Participants with Abnormalities in Clinical Laboratory Parameters
Number of participants with abnormalities in clinical laboratory values (which includes serum chemistry, hematology, coagulation, urinalysis, and serology) will be reported.
Measured: Up to approximately 3 years 2 months
Phase 2: Duration of Response (DoR)
DoR is defined as the time from the date of first documented response (PR or CR) until the date of documented progression or death from any case, whichever comes first, for participant who have PR or CR according to RECIST v1.1 by investigator review.
Measured: Up to approximately 3 years 2 months
Phase 2: Disease Control Rate (DCR)
DCR is defined as the percentage of participants who achieve a PR, CR, or stable disease using RECIST v1.1.
Measured: Up to approximately 3 years 2 months
Phase 2: Progression-Free Survival (PFS)
PFS is defined as the time from first dose date until the date of disease progression or death, whichever comes first, based on investigator assessment using RECIST v1.1 by investigator review.
Measured: Up to approximately 3 years 2 months
Phase 2: Overall Survival (OS)
OS is defined as the time from the date of administration of the first dose of study treatment until the date of death due to any cause.
Measured: Up to approximately 3 years 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2025
- Study start3 Mar 2026
- Primary completion30 Nov 2028 (estimated)
- Study completion30 Apr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
- More trials run by Janssen Research & Development, LLCThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Janssen Research & Development, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen Research & Development, LLC Clinical Trial, Study director, Janssen Research & Development, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07227025
- Sponsor's protocol ID
- 61186372PANSC2004
- Other IDs
- 61186372PANSC2004
- Acronym
- KaRAnaSa
- Status last verified
- Nov 2026
- First submitted
- 10 Nov 2025
- Last updated
- 3 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The data sharing policy of Johnson \& Johnson Innovative Medicine is available at www.innovativemedicine.jnj.com/our-innovation/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu.
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Study Evaluating the Safety and Efficacy of Amivantamab and Olomorasib Combination Therapy in Metastatic Non-small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT07227025
- Acronym / sponsor ID
- KaRAnaSa / 61186372PANSC2004
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Janssen Research & Development, LLCIndustry (pharma, biotech, devices)
- Study start
- 3 Mar 2026 (actual)
- Primary completion
- 30 Nov 2028 (estimated)
- Study completion
- 30 Apr 2029 (estimated)
- First posted
- 12 Nov 2025 (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 main purpose of this study is to find out the most suitable dose (recommended phase 2 combination dose [RP2CD]) of amivantamab and olomorasib combination therapy and to assess how well the combination slows down or prevents the growth of tumors in participants with KRAS G12C mutant metastatic non-small cell lung cancer (NSCLC: the most common type of lung cancer; metastatic: has spread to other parts of the body; KRAS G12C mutant: mutation [change] in the kirsten rat sarcoma viral oncogene homolog [KRAS] gene in tumor cells in which glycine [G] at position 12 is replaced with cystine [C]).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase 1: Combination Dose Selection | Experimental | Drug: Amivantamab, Drug: OlomorasibParticipants will receive amivantamab along with olomorasib to determine the RP2CD of the combination therapy until disease progression, significant toxicity, or until another criterion for discontinuation of study treatment is met. Eligible participants may have the option to transfer to a long-term extension (LTE) phase for continued access to study treatments. |
| Phase 2: Expansion | Experimental | Drug: Amivantamab, Drug: OlomorasibParticipants will receive amivantamab and olomorasib combination therapy at the RP2CD determined in Phase 1 until disease progression, significant toxicity, or until another criterion for discontinuation of study treatment is met. Eligible participants may have the option to transfer to LTE phase for continued access to study treatments. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Participant must have histologically or cytologically confirmed metastatic NSCLC characterized by a KRAS G12C mutation at the time of enrollment. For Phase 1: Participant must have progressed on or after, or have intolerance to, platinum-based chemotherapy and Programmed Death-Ligand 1 (PD-L1)-targeted immunotherapy given in combination or sequentially. Receipt of additional lines of prior therapy is permitted. Progression must have occurred on or after the most recent line of systemic anticancer therapy. For Phase 2: Participant must have progressed on or after platinum-based chemotherapy and PD-L1-targeted immunotherapy given in combination or sequentially. Progression must have occurred on or after the most recent line of systemic anticancer therapy. Receipt of additional lines of prior therapy is not permitted
- Participant must have at least 1 measurable lesion, according to RECIST version.1.1, that has not been previously irradiated
- May have brain metastases only if previously definitively, locally treated, and participant is clinically stable and asymptomatic for greater than (>) 2 weeks and is off or receiving low-dose corticosteroid treatment for at least 2 weeks prior to start of study treatment
- Can have a prior or concurrent second malignancy (other than the disease under study) with natural history or treatment course that is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s)
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Key exclusion criteria (5 listed)
- Participant has history of uncontrolled illness
- Suspected or known allergies, hypersensitivity, or intolerance to amivantamab excipients or olomorasib excipients
- Medical history of (non-infectious) interstitial lung disease (ILD)/pneumonitis, or has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
- Presence of primary driver mutations (epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK], mesenchymal-epithelial transition [MET], human epidermal growth factor receptor 2 [HER2], ROS1, neurotrophic tyrosine receptor kinase [NTRK], B-Raf proto-oncogene [BRAF], rearranged during Transfection [RET], neuroblastoma RAS viral oncogene homolog [NRAS], and other KRAS mutations besides G12C) as determined by local genomic testing
- Prior treatment with any KRAS inhibitor
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 |
|---|---|---|
| AmivantamabAlso: JNJ-61186372, RYBREVANTAmivantamab will be administered. | Drug | Phase 1: Combination Dose Selection, Phase 2: Expansion |
| OlomorasibAlso: LY3537982Olomorasib will be administered. | Drug | Phase 1: Combination Dose Selection, Phase 2: Expansion |
Primary outcome
Phase 1: Number of Participants with Adverse Events (AEs) by Severity
Time frame: Up to approximately 3 years 2 months
An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An assessment of severity grade will be made by the investigator according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 defined as follows: Grade 1 (mild; asymptomatic or mild symptoms; intervention not indicated); Grade 2 (moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living [ADL]); Grade 3 (severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL); Grade 4 (life-threatening consequences; urgent intervention indicated); Grade 5 (Death related to adverse event).
Phase 1: Number of Participants with Dose-Limiting Toxicities (DLTs)
Time frame: Up to approximately 3 years 2 months
DLT is defined as drug related adverse events and includes unacceptable non-hematologic toxicity, hematologic toxicity, pulmonary toxicity, or elevations in hepatic enzymes suggestive of drug-induced liver injury of Grade 3 or higher. Toxicities will be graded for severity according to the NCI-CTCAE, version 5.0.
Phase 2: Confirmed Objective Response Rate (ORR)
Time frame: Up to approximately 3 years 2 months
ORR is defined as the percentage of participants who achieve either a confirmed partial response (PR) or complete response (CR), using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 by investigator review. Confirmatory analysis may be performed using Blinded Independent Central Review (BICR).
6 secondary outcomes
Number of Participants with Adverse Events (AEs) by Severity
Time frame: Up to approximately 3 years 2 months
Number of Participants with Abnormalities in Clinical Laboratory Parameters
Time frame: Up to approximately 3 years 2 months
Phase 2: Duration of Response (DoR)
Time frame: Up to approximately 3 years 2 months
Phase 2: Disease Control Rate (DCR)
Time frame: Up to approximately 3 years 2 months
Phase 2: Progression-Free Survival (PFS)
Time frame: Up to approximately 3 years 2 months
Phase 2: Overall Survival (OS)
Time frame: Up to approximately 3 years 2 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2026.
- Individual participant dataSharing planned: Yes. The data sharing policy of Johnson \& Johnson Innovative Medicine is available at www.innovativemedicine.jnj.com/our-innovation/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu.
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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.
Janssen Research & Development, LLC Clinical Trial study director
Janssen Research & Development, LLC
12 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Amivantamab and Olomorasib in people with Carcinoma, Non-Small-Cell Lung, run by Janssen Research & Development, LLC at 12 sites in 5 countries.
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 5 inclusion and 5 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: looking for participants now, as of the sponsor's last update on 3 Nov 2026. 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 China, South Korea, Turkey (Türkiye), United States, Canada. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Study Contact (844-434-4210, Participate-In-This-Study1@its.jnj.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1: Number of Participants with Adverse Events (AEs) by Severity (time frame: Up to approximately 3 years 2 months). The study lists 3 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 3 Nov 2026.