Advanced CancerPhase 1NCT04330664
Adagrasib in Combination With TNO155 in Patients With Cancer (KRYSTAL 2)
A Phase 1 study testing MRTX849 and TNO155 in people with Advanced Cancer and Metastatic Cancer, run by Mirati Therapeutics Inc. at 17 sites in United States.
Trial summary
This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 in combination with TNO155 in patients with advanced solid tumors that have a KRAS G12C mutation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Cancer, Metastatic Cancer, Malignant Neoplastic Disease
- What is being tested?
- MRTX849 and TNO155
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 86 participants
- Where
- 17 sitesUnited States
- Study dates
- 7 Apr 2020to 24 Feb 2025
- 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
- Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation (phase 2 must be either Non-Small Cell Lung Cancer or Colorectal Cancer)
- Unresectable or metastatic disease
- No available treatment with curative intent
- Adequate organ function
Who cannot join
- History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions likely to alter absorption of study treatment or result in inability to swallow
- Other active cancer
- Cardiac abnormalities
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
United States17 sites
Local Institution - 002-804
Boston, Massachusetts, 02114
Local Institution - 002-808
Boston, Massachusetts, 02215
Local Institution - 002-828
Chicago, Illinois, 60611
Local Institution - 002-809 D
City of Saint Peters, Missouri, 63376
Local Institution - 002-809 B
Creve Coeur, Missouri, 63141
Local Institution - 002-805
Los Angeles, California, 90095
Local Institution - 002-810
Milwaukee, Wisconsin, 53226
Local Institution - 002-813
New York, New York, 10016
Local Institution - 002-806
New York, New York, 10065
Local Institution - 002-811
Novi, Michigan, 48377
Local Institution - 002-803
Orange, California, 92868
Local Institution - 002-801
San Antonio, Texas, 78229
Local Institution - 002-809 A
St Louis, Missouri, 63110
Local Institution - 002-809 C
St Louis, Missouri, 63129
Local Institution - 002-809
St Louis, Missouri, 63130
Local Institution - 002-809 E
St Louis, Missouri, 63136
Local Institution - 002-942
Wichita, Kansas, 67214
About this study
Official title: A Phase 1/2 Trial of MRTX849 in Combination With TNO155 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL 2
This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 in combination with TNO155 in patients with advanced solid tumors that have a KRAS G12C mutation.
Read the detailed description
This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 in combination with TNO155 in patients with advanced solid tumors with a KRAS G12C mutation. MRTX849 is an orally available small molecule inhibitor of KRAS G12C and TNO155 is a selective, orally bioavailable allosteric inhibitor of wild-type SHP2.
This study was terminated prior to phase 2 initiating. Only phase 1 of the study was conducted.
- Being tested
- MRTX849, TNO155
- Keywords
- KRAS G12C, Non-small cell lung cancer, Colorectal Cancer, Colon Cancer, Metastatic Cancer, Pancreatic Cancer, NSCLC, SHP2, Advanced Solid Tumors
- Medical subject headings
- Neoplasm Metastasis, Neoplasms, Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Colonic Neoplasms, Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRTX849Drug
Also called adagrasib
KRAS G12C Inhibitor
TNO155Drug
SHP2 Inhibitor
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 Dose Exploration | Experimental | Dose escalation of TNO155 to determine maximum tolerated dose of TNO155 in combination with MRTX849 Receives: Drug: MRTX849; Drug: TNO155 |
| Phase 1b Expansion | Experimental | Expansion cohort to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of MRTX849 in combination with TNO155 to recommend Phase 2 regimens Receives: Drug: MRTX849; Drug: TNO155 |
| Phase 2 | Experimental | Separate cohorts of patients stratified by histological diagnosis for evaluation of clinical activity to evaluate clinical activity of MRTX849 and TNO155 in combination Receives: Drug: MRTX849; Drug: TNO155 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Characterize the safety of MRTX849 and TNO155 in patients having advanced solid tumor malignancies with KRAS G12C mutation.
Number of participants with treatment related adverse events
Measured: 20 months
Evaluate the pharmacokinetics of MRTX849 and TNO155
Blood plasma concentration
Measured: 20 months
Secondary outcomes (2)
Establish maximum tolerated dose
Number of participants with dose limiting toxicity
Measured: 12 months
Evaluate clinical activity of MRTX849
Objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST)
Measured: 20 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2020
- Study start7 Apr 2020
- Primary completion29 Jul 2022
- Study completion24 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced CancerStudies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mirati Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04330664
- Sponsor's protocol ID
- CA239-0017
- Other IDs
- CA239-0017, 849-002
- Status last verified
- Mar 2025
- First submitted
- 30 Mar 2020
- Last updated
- 4 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
- Expanded access
- Available
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Trial of MRTX849 in Combination With TNO155 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL 2
- ClinicalTrials.gov ID
- NCT04330664
- Acronym / sponsor ID
- CA239-0017
- Keywords
- KRAS G12C, Non-small cell lung cancer, Colorectal Cancer, Colon Cancer, Metastatic Cancer, Pancreatic Cancer, NSCLC, SHP2
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 86 participants (actual)
- Lead sponsor
- Mirati Therapeutics Inc.Industry (pharma, biotech, devices)
- Collaborators
- Novartis
- Study start
- 7 Apr 2020 (actual)
- Primary completion
- 29 Jul 2022 (actual)
- Study completion
- 24 Feb 2025 (actual)
- First posted
- 1 Apr 2020 (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.
This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 in combination with TNO155 in patients with advanced solid tumors that have a KRAS G12C mutation.
Detailed description
This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 in combination with TNO155 in patients with advanced solid tumors with a KRAS G12C mutation. MRTX849 is an orally available small molecule inhibitor of KRAS G12C and TNO155 is a selective, orally bioavailable allosteric inhibitor of wild-type SHP2.
This study was terminated prior to phase 2 initiating. Only phase 1 of the study was conducted.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Phase 1 Dose Exploration | Experimental | Drug: MRTX849, Drug: TNO155Dose escalation of TNO155 to determine maximum tolerated dose of TNO155 in combination with MRTX849 |
| Phase 1b Expansion | Experimental | Drug: MRTX849, Drug: TNO155Expansion cohort to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of MRTX849 in combination with TNO155 to recommend Phase 2 regimens |
| Phase 2 | Experimental | Drug: MRTX849, Drug: TNO155Separate cohorts of patients stratified by histological diagnosis for evaluation of clinical activity to evaluate clinical activity of MRTX849 and TNO155 in combination |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation (phase 2 must be either Non-Small Cell Lung Cancer or Colorectal Cancer)
- Unresectable or metastatic disease
- No available treatment with curative intent
- Adequate organ function
Key exclusion criteria (3 listed)
- History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions likely to alter absorption of study treatment or result in inability to swallow
- Other active cancer
- Cardiac abnormalities
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 |
|---|---|---|
| MRTX849Also: adagrasibKRAS G12C Inhibitor | Drug | Phase 1 Dose Exploration, Phase 1b Expansion, Phase 2 |
| TNO155SHP2 Inhibitor | Drug | Phase 1 Dose Exploration, Phase 1b Expansion, Phase 2 |
Primary outcome
Characterize the safety of MRTX849 and TNO155 in patients having advanced solid tumor malignancies with KRAS G12C mutation.
Time frame: 20 months
Number of participants with treatment related adverse events
Evaluate the pharmacokinetics of MRTX849 and TNO155
Time frame: 20 months
Blood plasma concentration
2 secondary outcomes
Establish maximum tolerated dose
Time frame: 12 months
Evaluate clinical activity of MRTX849
Time frame: 20 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2025.
- BMS Clinical Trial InformationLink provided by the sponsor.
- BMS Clinical Trial Patient RecruitingLink provided by the sponsor.
- 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.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
17 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 MRTX849 and TNO155 in people with Advanced Cancer and Metastatic Cancer, run by Mirati Therapeutics Inc. at 17 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 4 inclusion and 3 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: finished, as of the sponsor's last update on 4 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Characterize the safety of MRTX849 and TNO155 in patients having advanced solid tumor malignancies with KRAS G12C mutation. (time frame: 20 months). 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 4 Apr 2025.