Tumor, SolidPhase 1NCT03454035
Ulixertinib/Palbociclib in Patients With Advanced Pancreatic and Other Solid Tumors
A Phase 1 study testing Ulixertinib and Palbociclib in people with Tumor, Solid and Pancreatic Cancer, run by UNC Lineberger Comprehensive Cancer Center at 1 site in United States.
Trial summary
This phase I study is designed to establish the safety, maximally tolerated dose (MTD) and recommended phase II dose (RP2D) of the ERK inhibitor ulixertinib (BVD-523) when combined with the CDK4/6 inhibitor palbociclib. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Tumor, Solid, Pancreatic Cancer, Melanoma
- What is being tested?
- Ulixertinib and Palbociclib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Jan 2018to 3 Feb 2028
- Phase
- Phase 1
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
- Age ≥ 18 years at the time of consent (no upper age limit)
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
- Tumor Eligibility:
- Dose escalation cohorts: Histologically confirmed advanced solid tumor refractory to standard of care therapy, or for which there is no accepted standard of care
- Expansion cohort (at RP2D): metastatic pancreatic cancer or malign melanoma patients who have received at least one line of therapy in the metastatic setting
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- Expansion cohort (at RP2D) for histologically confirmed unresectable stage III or stage IV melanoma with the following additional eligibility requirements:
- Tumors molecular profiling genetic aberrations: NRASG12/G13/Q61, KRASG12/G13, HRASG12/G13, any amplifications of the NRAS, KRAS, or HRAS genes. For NF1 mutations, subjects with loss-of-function NF1mutations and without any BRAFV600 mutations will be enrolled.
- Documented disease refractory to at least one PD1/PD-L1 inhibitor, defined as disease progression following at least two infusions of the same drug.
- Subjects with RAS-mutant and NF1-mutant (no concurrent BRAFV600 mutations) melanoma that have not taken prior immune checkpoint inhibitors will be allowed if they are not eligible to receive prior immune checkpoint inhibitors due to requirement for immunosuppression
- Measurable or non-measurable (but evaluable) disease according to RECIST v1.1 for dose escalating cohorts; measurable disease as per RECIST v1.1 required for expansion cohort
- Life expectancy ≥ 12 weeks
- Recovered from all reversible acute toxic effects of last anti-cancer treatment (other than alopecia) to ≤Grade 1 or baseline. Patients with baseline neuropathy that is ≤ grade 2 are eligible for enrollment.
- Demonstrate adequate organ function as defined in the table below; all screening labs to be obtained within 28 days prior to day -6 of ulixertinib
- Hemoglobin (Hgb) ≥ 9 g/dL Absolute Neutrophil Count (ANC) ≥ 1,500 /mm3 Platelets ≥ 100,000/mm3 Creatinine ≤1.5 x upper limit of normal (ULN) or Calculated creatinine clearance ≥ 60 mL/min using the Cockcroft-Gault formula Bilirubin ≤ 1.5 x ULN Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 x ULN; if tumor involvement of the liver ≤ 5 x ULN
- Adequate cardiac function; left ventricular ejection fraction (LVEF) >50% as assessed by ultrasound/echocardiography (ECHO) and corrected QT interval (QTc)
- Females of childbearing potential must have a negative serum pregnancy test within 3 days prior to day -6 of ulixertinib. NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months
- Females of childbearing potential and males must be willing to abstain from heterosexual activity* or use effective methods of contraception from the time of informed consent until 120 days after treatment discontinuation. Acceptable contraception methods can be comprised of an intrauterine device (IUD), vasectomy of a female subject's male partner, contraceptive rod implanted into the skin, OR use of two of the following: diaphragm with spermicide (cannot be used in conjunction with cervical cap/spermicide), cervical cap with spermicide (nulliparous women only), contraceptive sponge (nulliparous women only), male condom or female condom (cannot be used together), hormonal contraceptive.] *Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
- Subject is willing and able to comply with study procedures based on the judgment of the investigator or protocol designee.
- Willing to provide archival tissue (if available) and consent to mandatory pretreatment and on-treatment biopsy as deemed safe by the treating physician (expansion cohort only) for research purposes only.
Who cannot join
- Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on the study)
- Treatment with any cancer-directed therapy (chemotherapy, hormonal therapy, biologic, radiation or immunotherapy, etc.) or investigational drug within 28 days or 5 half-lives (whichever is shorter) prior to day -6 of ulixertinib
- A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR).
- Major surgery within 28 days prior to day -6 of ulixertinib
- Not willing to avoid grapefruit, grapefruit juices, grapefruit hybrids, oranges, pummelos, and exotic citrus fruits from 7 days prior to day -6 of ulixertinib and during the entire study due to potential CYP3A4 interaction with the study medications.
- Intake of any herbal preparations or medications (including, but not limited to, Saint John's Wort and ginkgo biloba) and dietary supplements within 7 days prior to day -6 of ulixertinib due to potential CYP3A4 interaction with the study medications
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- Unable or unwilling to discontinue use of any drug known to be a strong inhibitor of CYP3A4, CYP1A2 or CYP2D6 or strong inducer of CYP3A4 (prohibited inducers and inhibitors must be discontinued within 2 weeks prior to day -6 of ulixertinib; see section 10.3 Appendix C)
- Unable or unwilling to discontinue use of any drug known to be a sensitive CYP3A4 substrate with a narrow therapeutic index as defined in the protocol.
- Central nervous system metastases are allowed only for patients RAS-mutated and NF1-mutant melanoma cohorts (1) no leptomeningeal disease is present, (2) Intracranial disease is controlled by prior therapies, as evidenced by brain imaging 2 weeks post treatment indicating no new intracranial disease, (3) stable or decreasing dose of steroids is provided patient on ≤ 20mg of prednisone or it's equivalent daily.
- Any important medical illness or abnormal laboratory finding that would increase the risk of participating in the study (based on the investigator's judgment)
- Psychiatric illness/social situations that would limit compliance with study requirements
- Has a known additional malignancy that is active and/or progressive requiring treatment; non-melanoma skin cancers, non-invasive bladder cancer, and carcinoma in situ of the cervix, prior history of prostate cancer provided the patient is not undergoing active systemic treatment other than hormonal therapy and has documented PSA that is undetectable (<0.2ng/mL), prostate carcinoma in remission and did not receive systemic treatment, papillary thyroid cancer did not receive adjuvant radioactive iodine, Stage Rai stage 0 Chronic lymphocytic leukemia does not require systemic treatment, lymphoma, hairy-cell leukemia, or myelodysplasia is in complete remission and or other cancer for which the patient has been disease-free for at least two years.
- Has a known additional malignancy that is active and/or progressive requiring treatment.
- Impaired GI function or GI disease that may significantly impair absorption (e.g., inflammatory bowel disease (IBD), malabsorption syndrome, small bowel resection, uncontrolled vomiting or diarrhea)
- Inability to swallow oral medications
- Patients with autoimmune diseases that require systemic corticosteroid treatment >20 mg methylprednisolone equivalent.
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
Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Melissa Flores, melissa_flores@med.unc.edu
Stergios Moschos, (866) 869-1856
About this study
Official title: Ulixertinib (BVD-523) in Combination With Palbociclib in Patients With Advanced Solid Tumors With Expansion Cohort in Previously Treated Metastatic Pancreatic Cancer and Metastatic RAS-mutant and NF1-mutant (no BRAFV600 Mutations) Melanoma
This phase I study is designed to establish the safety, maximally tolerated dose (MTD) and recommended phase II dose (RP2D) of the ERK inhibitor ulixertinib (BVD-523) when combined with the CDK4/6 inhibitor palbociclib.
Read the detailed description
This phase I study is designed to establish the safety, maximally tolerated dose (MTD) and recommended phase II dose (RP2D) of the ERK inhibitor ulixertinib (BVD-523) when combined with the CDK4/6 inhibitor palbociclib.
Up to a maximum of 30 adult patients will be enrolled in the 5 possible dose escalation cohorts. These patients will have histologically confirmed advanced solid tumor disease refractory to standard of care therapy, or for which there is no accepted standard of care.
An expansion cohort enrollment will start After RP2D of ulixertinib combined with palbociclib is defined. Then 15 patients with metastatic pancreatic cancer and 15 patients with RAS-mutant melanoma will be enrolled.
Note:Pancreatic cancer expansion cohort and all solid tumor cohorts are closed to enrollment.
- Conditions
- Tumor, Solid, Pancreatic Cancer, Melanoma
- Being tested
- Ulixertinib, Palbociclib
- Medical subject headings
- Neoplasms, Pancreatic Neoplasms, Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UlixertinibDrug
Also called BVD-523
Ulixertinib 300mg, orally, twice a day concomitantly with palbociclib
PalbociclibDrug
Also called Ibrance
Drug: Palbociclib 125mg, orally, once a day concomitantly with ulixertinib
| Study group | Role | What they receive |
|---|---|---|
| Open-label, single arm Phase I | Experimental | Ulixertinib added to palbociclib Receives: Drug: Ulixertinib; Drug: Palbociclib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
MTD of ulixertinib in combination with palbociclib in patients with advanced solid tumors of ulixertinib in combination with palbociclib in patients with advanced solid tumors
Measured: Five weeks
Overall Survival
For Expansion Cohort: To estimate overall survival (OS) after treatment with the recommended phase 2 dose of ulixertinib in combination with palbociclib in an expansion cohort of patients with metastatic pancreatic cancer
Measured: 6 months after treatment
Secondary outcomes (5)
Safety (number of patients with adverse events)
Number of patients with adverse events
Measured: 5 weeks
Objective Response Rate
To estimate objective response rate (ORR) after treatment with ulixertinib in combination with palbociclib
Measured: 8 weeks
Progression-free survival
To estimate progression-free survival (PFS) after treatment with ulixertinib in combination with palbociclib
Measured: Up to two years after treatment
Overall Survival
For Expansion Cohort: To estimate overall survival (OS) after treatment with the recommended phase 2 dose of ulixertinib in combination with palbociclib in an expansion cohort of patients with metastatic pancreatic cancer
Measured: Up to two years after treatment
Cancer Antigen 19-9 (CA19-9) response
For Expansion Cohort: To estimate CA19-9 response after treatment with ulixertinib in combination with palbociclib
Measured: Through treatment completion, approximately 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2018
- Study start30 Jan 2018
- Primary completion3 Feb 2028 (estimated)
- Study completion3 Feb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tumor, SolidStudies of the same condition, open and under way.
- More trials run by UNC Lineberger Comprehensive Cancer CenterThe 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
- Model description
- This is a standard 3+3 dose escalation design.
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- UNC Lineberger Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- BioMed Valley Discoveries, Inc, Pfizer
- Responsible party
- Sponsor
- Investigators
- Stergios Moschos, MD, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03454035
- Sponsor's protocol ID
- LCCC1736
- Status last verified
- Aug 2026
- First submitted
- 5 Feb 2018
- Last updated
- 19 Aug 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ulixertinib (BVD-523) in Combination With Palbociclib in Patients With Advanced Solid Tumors With Expansion Cohort in Previously Treated Metastatic Pancreatic Cancer and Metastatic RAS-mutant and NF1-mutant (no BRAFV600 Mutations) Melanoma
- ClinicalTrials.gov ID
- NCT03454035
- Acronym / sponsor ID
- LCCC1736
- Conditions
- Tumor, Solid, Pancreatic Cancer, Melanoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- UNC Lineberger Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- BioMed Valley Discoveries, Inc, Pfizer
- Study start
- 30 Jan 2018 (actual)
- Primary completion
- 3 Feb 2028 (estimated)
- Study completion
- 3 Feb 2028 (estimated)
- First posted
- 5 Mar 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.
This phase I study is designed to establish the safety, maximally tolerated dose (MTD) and recommended phase II dose (RP2D) of the ERK inhibitor ulixertinib (BVD-523) when combined with the CDK4/6 inhibitor palbociclib.
Detailed description
This phase I study is designed to establish the safety, maximally tolerated dose (MTD) and recommended phase II dose (RP2D) of the ERK inhibitor ulixertinib (BVD-523) when combined with the CDK4/6 inhibitor palbociclib.
Up to a maximum of 30 adult patients will be enrolled in the 5 possible dose escalation cohorts. These patients will have histologically confirmed advanced solid tumor disease refractory to standard of care therapy, or for which there is no accepted standard of care.
An expansion cohort enrollment will start After RP2D of ulixertinib combined with palbociclib is defined. Then 15 patients with metastatic pancreatic cancer and 15 patients with RAS-mutant melanoma will be enrolled.
Note:Pancreatic cancer expansion cohort and all solid tumor cohorts are closed to enrollment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a standard 3+3 dose escalation design.
| Arm | Type | Receives |
|---|---|---|
| Open-label, single arm Phase I | Experimental | Drug: Ulixertinib, Drug: PalbociclibUlixertinib added to palbociclib |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
- Age ≥ 18 years at the time of consent (no upper age limit)
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
- Tumor Eligibility:
- Measurable or non-measurable (but evaluable) disease according to RECIST v1.1 for dose escalating cohorts; measurable disease as per RECIST v1.1 required for expansion cohort
Key exclusion criteria (16 listed)
- Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on the study)
- Treatment with any cancer-directed therapy (chemotherapy, hormonal therapy, biologic, radiation or immunotherapy, etc.) or investigational drug within 28 days or 5 half-lives (whichever is shorter) prior to day -6 of ulixertinib
- A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR).
- Major surgery within 28 days prior to day -6 of ulixertinib
- Not willing to avoid grapefruit, grapefruit juices, grapefruit hybrids, oranges, pummelos, and exotic citrus fruits from 7 days prior to day -6 of ulixertinib and during the entire study due to potential CYP3A4 interaction with the study medications.
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 |
|---|---|---|
| UlixertinibAlso: BVD-523Ulixertinib 300mg, orally, twice a day concomitantly with palbociclib | Drug | Open-label, single arm Phase I |
| PalbociclibAlso: IbranceDrug: Palbociclib 125mg, orally, once a day concomitantly with ulixertinib | Drug | Open-label, single arm Phase I |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: Five weeks
MTD of ulixertinib in combination with palbociclib in patients with advanced solid tumors of ulixertinib in combination with palbociclib in patients with advanced solid tumors
Overall Survival
Time frame: 6 months after treatment
For Expansion Cohort: To estimate overall survival (OS) after treatment with the recommended phase 2 dose of ulixertinib in combination with palbociclib in an expansion cohort of patients with metastatic pancreatic cancer
5 secondary outcomes
Safety (number of patients with adverse events)
Time frame: 5 weeks
Objective Response Rate
Time frame: 8 weeks
Progression-free survival
Time frame: Up to two years after treatment
Overall Survival
Time frame: Up to two years after treatment
Cancer Antigen 19-9 (CA19-9) response
Time frame: Through treatment completion, approximately 1 year
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 19 Aug 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.
Stergios Moschos, MD principal investigator
University of North Carolina, Chapel Hill
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ulixertinib and Palbociclib in people with Tumor, Solid and Pancreatic Cancer, run by UNC Lineberger Comprehensive Cancer Center 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 20 inclusion and 16 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 19 Aug 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 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?
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 Brian Burgess (919-966-4432, brian_burgess@med.unc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) (time frame: Five weeks). 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 19 Aug 2026.