Ulixertinib/Palbociclib in Patients With Advanced Pancreatic and Other Solid Tumors

NCT03454035 | Recruiting Phase 1 FDA Drug

• 1 other identifier: LCCC1736
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Tumor, Solid; Pancreatic Cancer; Melanoma

Outcome Measures

Primary Outcomes (2)

• 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

  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

  6 months after treatment

Secondary Outcomes (5)

• Safety (number of patients with adverse events)

  5 weeks

• Objective Response Rate

  8 weeks

• Progression-free survival

  Up to two years after treatment

• Overall Survival

  Up to two years after treatment

• Cancer Antigen 19-9 (CA19-9) response

  Through treatment completion, approximately 1 year

Study Arms (1)

Open-label, single arm Phase I

EXPERIMENTAL

Ulixertinib added to palbociclib

Drug: Ulixertinib; Drug: Palbociclib

Interventions

Ulixertinib DRUG

Ulixertinib 300mg, orally, twice a day concomitantly with palbociclib

Also known as: BVD-523

Open-label, single arm Phase I

Palbociclib DRUG

Drug: Palbociclib 125mg, orally, once a day concomitantly with ulixertinib

Also known as: Ibrance

Open-label, single arm Phase I

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• BioMed Valley Discoveries, Inc: collaborator
• Pfizer: collaborator

Study Sites (1)

Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

RECRUITING

MeSH Terms

Conditions

Neoplasms; Pancreatic Neoplasms; Melanoma

Interventions

ulixertinib; palbociclib

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Stergios Moschos, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Brian Burgess

CONTACT

919-966-4432; brian_burgess@med.unc.edu

Catherine Griffin

CONTACT

919-966-4432; catherine_griffin@med.unc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a standard 3+3 dose escalation design.

Study Record Dates

• First Submitted: February 5, 2018
• First Posted: March 5, 2018
• Study Start: January 30, 2018
• Primary Completion (Estimated): July 15, 2026
• Study Completion (Estimated): November 24, 2026
• Last Updated: September 11, 2025

Record last verified: 2025-09

Locations

US (1)