Metastatic Colorectal Cancer (CRC)Phase 1/2NCT07912593
Phase 1/2, Open-label Study of ETX-929, a KRAS Inhibitor in Participants With Advanced Solid Tumors
A Phase 1/2 study testing ETX-929 dose escalation and ETX-929 dose escalation in combination with cetuximab in people with Metastatic Colorectal Cancer (CRC) and Pancreatic Ductal Adenocarcinoma (PDAC), run by Ensem Therapeutics at 1 site in United States.
Trial summary
This is a Phase 1/2, open-label, multi-center study to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of ETX-929 in participants with advanced solid tumors harboring a Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer (CRC), Pancreatic Ductal Adenocarcinoma (PDAC), Non-squamous, Non-Small Cell Lung Cancer
- What is being tested?
- ETX-929 dose escalation and ETX-929 dose escalation in combination with cetuximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 320 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Oct 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
- Metastatic or locally advanced and unresectable solid tumor that has progressed on or after at least one available therapy.
- Tumor harboring a KRAS mutation.
- An ECOG performance status score of 0 or 1.
- Adequate organ function.
Who cannot join
- Has history (within ≤2 years before screening) of a solid tumor or hematological malignancy that is histologically distinct from the cancers being studied.
- Has symptomatic brain or spinal metastases or a known or suspected history of untreated or uncontrolled central nervous system (CNS) involvement.
- Has received treatment with any local or systemic anticancer therapy or investigational anticancer agent within 14 days prior to start of treatment.
- Has toxicities from previous anticancer therapies that have not resolved to baseline levels with the exception of alopecia and peripheral neuropathy.
- Has had radiotherapy outside the target tumor lesions within 14 days prior to start of treatment.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
NEXT
Fairfax, Virginia, 22031
Maybelle De La Rosa, 703-783-4518, mdelarosa@nextoncology.com
Alex Spira, MD, PhD, FACP
About this study
Official title: A Phase 1/2, First-in-Human Study of ETX-929, a Pan-KRAS Inhibitor, as Monotherapy and in Combination With Other Anticancer Therapies in Participants With KRAS-Altered Advanced Solid Tumors
This is a Phase 1/2, open-label, multi-center study to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of ETX-929 in participants with advanced solid tumors harboring a Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation.
Read the detailed description
Part A will evaluate escalating doses of ETX-929 as monotherapy in participants with advanced solid tumors. Part B will evaluate escalating doses of ETX-929 as combination therapy with fixed dose cetuximab in participants. Part C and Part D will expand enrollment of ETX-929 as monotherapy and in combination with cetuximab at the recommended doses from escalation.
Each study part will include a 28-day screening period, followed by treatment with ETX-929 monotherapy or combination therapy.
- Conditions
- Metastatic Colorectal Cancer (CRC), Pancreatic Ductal Adenocarcinoma (PDAC), Non-squamous, Non-Small Cell Lung Cancer, Endometrial Adenocarcinoma, Ovarian Adenocarcinoma, Primary Peritoneal Carcinoma
- Being tested
- ETX-929 dose escalation, ETX-929 dose escalation in combination with cetuximab
- Keywords
- KRAS
- Medical subject headings
- Colorectal 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.
ETX-929 dose escalationDrug
ETX-929 is a pan-KRAS Inhibitor in the form of an oral capsule that will be taken once per day in 21-day cycles, to evaluate escalating dose levels.
ETX-929 dose escalation in combination with cetuximabDrug
ETX-929 is a pan-KRAS Inhibitor in the form of an oral capsule. ETX-929 will be taken in combination with cetuximab in 28-day cycles, to evaluate escalating dose levels. EXT-929 is an oral capsule that will be taken once per day. Cetuximab will be administered intravenously every two weeks.
| Study group | Role | What they receive |
|---|---|---|
| Part A Dose Escalation Monotherapy | Experimental | Part A is a dose escalation monotherapy of ETX-929 in advanced solid tumors with KRAS alterations. Receives: Drug: ETX-929 dose escalation |
| Part B Dose Escalation Combination Therapy | Experimental | Part B is a dose escalation combination therapy in advanced solid tumors with KRAS alterations. The study treatment will be ETX-929, a pan-KRAS inhibitor, in combination with cetuximab at a fixed dose. Receives: Drug: ETX-929 dose escalation in combination with cetuximab |
| Part C Dose Expansion | Experimental | Part C will evaluate ETX-929 at the recommended Phase 2 dose (RP2D[s]) established in Part A. Receives: Drug: ETX-929 dose escalation |
| Part D Dose Expansion Combination Therapy | Experimental | Part D will evaluate ETX-929 at the recommended Phase 2 dose (RP2D[s]) established in Part A. Receives: Drug: ETX-929 dose escalation in combination with cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate Safety and Tolerability of ETX-929 monotherapy in Part A and ETX-929 plus cetuximab combination therapy in Part B
Proportion of participants who experience at least 1 Dose Limiting Toxicity (DLT)
Measured: First Cycle (21 days in Part A and 28 days in Part B)
Evaluate Safety and Tolerability of ETX-929 monotherapy in Part A and ETX-929 plus cetuximab combination therapy in Part B
Incidence of AEs, treatment discontinuations due to AEs, changes from baseline in laboratory assessments, ECGs and vital signs
Measured: Average of 6 months
Select the Recommended Phase 2 Dose(s) (RP2D)
Safety Parameters as described for primary outcomes
Measured: Average of 6 months
Evaluate efficacy of ETX-929 monotherapy and ETX-929 in combination with cetuximab at the RP2D(s) in Part B and Part D
ORR according to RECIST v1.1
Measured: Average of 6 months
Secondary outcomes (11)
Characterize the Cmax (PK) of ETX-929 monotherapy in Part A and ETX-929 plus cetuximab combination therapy in Part B
Maximum observed plasma concentration (Cmax) of ETX-929
Measured: First treatment cycle (21 day-cycles in Part A and 28-day cycles in Part B)
Characterize the Tmax (PK) of ETX-929 monotherapy in Part A and ETX-929 plus cetuximab combination therapy in Part B
Calculated time to reach maximum observed plasma concentration of ETX-929
Measured: First treatment cycle (21 day-cycles in Part A and 28-day cycles in Part B)
Characterize the AUC (PK) of ETX-929 monotherapy in Part A and ETX-929 plus cetuximab combination therapy in Part B
Calculated area under the plasma concentration curve (AUC) of ETX-929
Measured: First treatment cycle (21 day-cycles in Part A and 28-day cycles in Part B)
Assess preliminary efficacy of ETX-929 monotherapy in Part A and ETX-636 plus cetuximab combination therapy in Part B
Objective response rate (ORR) and clinical benefit rate (CBR) based on RECIST v1.1
Measured: Average of 6 months
Evaluate measures of efficacy of ETX-929 monotherapy in Part C and ETX-929 plus cetuximab combination therapy at the RP2D(s) in Part D
Time to response (TTR) according to RECIST v1.1
Measured: Average of 6 months
Evaluate additional measures of efficacy of ETX-929 monotherapy in Part A and ETX-929 plus cetuximab combination therapy at the RP2D(s) in Part C
Duration of response (DoR) according to RECIST v1.1
Measured: Average of 6 months
Evaluate additional measures of efficacy of ETX-929 monotherapy in Part A and ETX-929 plus cetuximab combination therapy at the RP2D(s) in Part C
Disease control rate (DCR) according to RECIST v1.1
Measured: Average of 6 months
Evaluate additional measures of efficacy of ETX-929 monotherapy in Part A and ETX-929 plus cetuximab combination therapy at the RP2D(s) in Part C
Progression free survival (PFS) according to RECIST v1.1
Measured: Average of 6 months
Evaluate Safety of ETX-929 monotherapy in Part A and C, and and ETX-929 plus cetuximab combination therapy at the RP2Ds in Part B and Part D
Incidence of adverse events graded according to CTCAE v5.0
Measured: Average of 6 months
Evaluate Tolerability of ETX-929 monotherapy in Part A and C, and ETX-929 plus cetuximab combination therapy at the RP2Ds in Part B and Part D
Incidence of adverse events graded according to CTCAE v5.0
Measured: Average of 6 months
Characterize the PK of ETX-929 using population PK modeling
Plasma concentrations
Measured: Average of 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2026
- Study start22 Oct 2026
- Primary completion30 Oct 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 Metastatic Colorectal Cancer (CRC)Studies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 320 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ensem Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07912593
- Sponsor's protocol ID
- ETX929-C-001
- Status last verified
- Oct 2026
- First submitted
- 28 Oct 2026
- Last updated
- 3 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
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, First-in-Human Study of ETX-929, a Pan-KRAS Inhibitor, as Monotherapy and in Combination With Other Anticancer Therapies in Participants With KRAS-Altered Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT07912593
- Acronym / sponsor ID
- ETX929-C-001
- Conditions
- Metastatic Colorectal Cancer (CRC), Pancreatic Ductal Adenocarcinoma (PDAC), Non-squamous, Non-Small Cell Lung Cancer, Endometrial Adenocarcinoma, Ovarian Adenocarcinoma, Primary Peritoneal Carcinoma
- Keywords
- KRAS
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 320 participants (estimated)
- Lead sponsor
- Ensem TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 22 Oct 2026 (actual)
- Primary completion
- 30 Oct 2028 (estimated)
- Study completion
- 30 Apr 2029 (estimated)
- First posted
- 3 Nov 2026 (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 is a Phase 1/2, open-label, multi-center study to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of ETX-929 in participants with advanced solid tumors harboring a Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation.
Detailed description
Part A will evaluate escalating doses of ETX-929 as monotherapy in participants with advanced solid tumors. Part B will evaluate escalating doses of ETX-929 as combination therapy with fixed dose cetuximab in participants. Part C and Part D will expand enrollment of ETX-929 as monotherapy and in combination with cetuximab at the recommended doses from escalation.
Each study part will include a 28-day screening period, followed by treatment with ETX-929 monotherapy or combination therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part A Dose Escalation Monotherapy | Experimental | Drug: ETX-929 dose escalationPart A is a dose escalation monotherapy of ETX-929 in advanced solid tumors with KRAS alterations. |
| Part B Dose Escalation Combination Therapy | Experimental | Drug: ETX-929 dose escalation in combination with cetuximabPart B is a dose escalation combination therapy in advanced solid tumors with KRAS alterations. The study treatment will be ETX-929, a pan-KRAS inhibitor, in combination with cetuximab at a fixed dose. |
| Part C Dose Expansion | Experimental | Drug: ETX-929 dose escalationPart C will evaluate ETX-929 at the recommended Phase 2 dose (RP2D[s]) established in Part A. |
| Part D Dose Expansion Combination Therapy | Experimental | Drug: ETX-929 dose escalation in combination with cetuximabPart D will evaluate ETX-929 at the recommended Phase 2 dose (RP2D[s]) established in Part A. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Metastatic or locally advanced and unresectable solid tumor that has progressed on or after at least one available therapy.
- Tumor harboring a KRAS mutation.
- An ECOG performance status score of 0 or 1.
- Adequate organ function.
Key exclusion criteria (5 listed)
- Has history (within ≤2 years before screening) of a solid tumor or hematological malignancy that is histologically distinct from the cancers being studied.
- Has symptomatic brain or spinal metastases or a known or suspected history of untreated or uncontrolled central nervous system (CNS) involvement.
- Has received treatment with any local or systemic anticancer therapy or investigational anticancer agent within 14 days prior to start of treatment.
- Has toxicities from previous anticancer therapies that have not resolved to baseline levels with the exception of alopecia and peripheral neuropathy.
- Has had radiotherapy outside the target tumor lesions within 14 days prior to start of treatment.
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 |
|---|---|---|
| ETX-929 dose escalationETX-929 is a pan-KRAS Inhibitor in the form of an oral capsule that will be taken once per day in 21-day cycles, to evaluate escalating dose levels. | Drug | Part A Dose Escalation Monotherapy, Part C Dose Expansion |
| ETX-929 dose escalation in combination with cetuximabETX-929 is a pan-KRAS Inhibitor in the form of an oral capsule. ETX-929 will be taken in combination with cetuximab in 28-day cycles, to evaluate escalating dose levels. EXT-929 is an oral capsule that will be taken once per day. Cetuximab will be administered intravenously every two weeks. | Drug | Part B Dose Escalation Combination Therapy, Part D Dose Expansion Combination Therapy |
Primary outcome
Evaluate Safety and Tolerability of ETX-929 monotherapy in Part A and ETX-929 plus cetuximab combination therapy in Part B
Time frame: First Cycle (21 days in Part A and 28 days in Part B)
Proportion of participants who experience at least 1 Dose Limiting Toxicity (DLT)
Evaluate Safety and Tolerability of ETX-929 monotherapy in Part A and ETX-929 plus cetuximab combination therapy in Part B
Time frame: Average of 6 months
Incidence of AEs, treatment discontinuations due to AEs, changes from baseline in laboratory assessments, ECGs and vital signs
Select the Recommended Phase 2 Dose(s) (RP2D)
Time frame: Average of 6 months
Safety Parameters as described for primary outcomes
Evaluate efficacy of ETX-929 monotherapy and ETX-929 in combination with cetuximab at the RP2D(s) in Part B and Part D
Time frame: Average of 6 months
ORR according to RECIST v1.1
11 secondary outcomes
Characterize the Cmax (PK) of ETX-929 monotherapy in Part A and ETX-929 plus cetuximab combination therapy in Part B
Time frame: First treatment cycle (21 day-cycles in Part A and 28-day cycles in Part B)
Characterize the Tmax (PK) of ETX-929 monotherapy in Part A and ETX-929 plus cetuximab combination therapy in Part B
Time frame: First treatment cycle (21 day-cycles in Part A and 28-day cycles in Part B)
Characterize the AUC (PK) of ETX-929 monotherapy in Part A and ETX-929 plus cetuximab combination therapy in Part B
Time frame: First treatment cycle (21 day-cycles in Part A and 28-day cycles in Part B)
Assess preliminary efficacy of ETX-929 monotherapy in Part A and ETX-636 plus cetuximab combination therapy in Part B
Time frame: Average of 6 months
Evaluate measures of efficacy of ETX-929 monotherapy in Part C and ETX-929 plus cetuximab combination therapy at the RP2D(s) in Part D
Time frame: Average of 6 months
Evaluate additional measures of efficacy of ETX-929 monotherapy in Part A and ETX-929 plus cetuximab combination therapy at the RP2D(s) in Part C
Time frame: Average of 6 months
Evaluate additional measures of efficacy of ETX-929 monotherapy in Part A and ETX-929 plus cetuximab combination therapy at the RP2D(s) in Part C
Time frame: Average of 6 months
Evaluate additional measures of efficacy of ETX-929 monotherapy in Part A and ETX-929 plus cetuximab combination therapy at the RP2D(s) in Part C
Time frame: Average of 6 months
Evaluate Safety of ETX-929 monotherapy in Part A and C, and and ETX-929 plus cetuximab combination therapy at the RP2Ds in Part B and Part D
Time frame: Average of 6 months
Evaluate Tolerability of ETX-929 monotherapy in Part A and C, and ETX-929 plus cetuximab combination therapy at the RP2Ds in Part B and Part D
Time frame: Average of 6 months
Characterize the PK of ETX-929 using population PK modeling
Time frame: Average of 6 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.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ETX-929 dose escalation and ETX-929 dose escalation in combination with cetuximab in people with Metastatic Colorectal Cancer (CRC) and Pancreatic Ductal Adenocarcinoma (PDAC), run by Ensem Therapeutics at 1 site 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 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 1 site 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 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 Lori Cykowski (1-617-383-4993, lori.cykowski@Ensemtx.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluate Safety and Tolerability of ETX-929 monotherapy in Part A and ETX-929 plus cetuximab combination therapy in Part B (time frame: First Cycle (21 days in Part A and 28 days in Part B)). The study lists 4 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.