Study of Bemcentinib Plus Pacritinib In Patients With Advanced Lung Adenocarcinoma

NCT06516887 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: CTMS# 24-00205R01CA269766-02
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase Ib/II, open-label, single institution dose-escalation, safety, pharmacokinetics, pharmacodynamic and efficacy study.

Conditions

Advanced Lung Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Progression Free Survival (PFS)

  PFS will be defined as the time from the date of randomization to the date of disease progression or death (any cause), whichever occurs first. Subjects completing study follow-up or initiating a new anticancer therapy prior to documented PD will be censored in the PFS analysis at the last known date the subject was documented progression free prior to completing follow-up or initiating the new therapy.

  Up to 48 months

• Overall Response Rate

  Overall response rate is defined as the proportion of patients who have a partial or complete response to therapy.

  Up to 48 months

Secondary Outcomes (2)

• Overall Survival (OS)

  Up to 48 months

• Clinical Benefit Rate

  Up to 48 months

Study Arms (2)

Pharmacokinetic Phase 1b (PK) Study Cohort

EXPERIMENTAL

Patients will receive bemcentinib and pacritinib in combination from Days 1 to Day 28. PK samples will be collected on Day 1 (pre-dose, 4, 6h), pre-dose Day 2, Day 7 (pre-dose, 4h and 6h post-dose), pre-dose Day 8, pre-dose Day 14, and Day 22 (pre-dose and 6h post-dose) samples. The Day 22 sample will cover the steady state values for both compounds. Six dose levels of combination treatments will be considered: * Dose level -1: pacritinib 100 mg oral dose (p.o.) daily + bemcentinib 50 mg p.o. daily; * Dose level 1: pacritinib 100 mg oral dose (p.o.) twice daily (BID) + bemcentinib 50 mg p.o. daily; * Dose level 2: pacritinib 100 mg p.o. BID + bemcentinib 75 mg p.o. daily; * Dose level 3: pacritinib 100 mg BID + bemcentinib 100 mg p.o. daily; * Dose level 4: pacritinib 200 mg BID + bemcentinib 100 mg p.o. daily; * Dose level 5: pacritinib 200 mg BID + bemcentinib 125 mg p.o. daily.

Drug: bemcentinib; Drug: pacritinib

Phase II Cohort

EXPERIMENTAL

Of these participants taking the Maximum tolerated dose, up to 15 will undergo a biopsy. Progression free survival will be the primary objective of this study phase.

Drug: bemcentinib; Drug: pacritinib

Interventions

bemcentinib DRUG

Bemcentinib has been investigated in a phase I/II clinical trials for solid tumors. Phase I and II clinical studies of BGB324 are ongoing in non-small cell carcinoma, in which combinations with other agents such as Phase I study of docetaxel (NCT02922777), erlotinib (NCT02424617), and pembrolizumab (NCT03184571) are also being investigated. In a phase I dose escalation study of bemcentinib in combination with docetaxel study, patients with treatment naïve, advanced lung adenocarcinoma receive docetaxel 75 mg/m2 given IV every 21 days in combination with bemcentinib. Bemcentinib dose will be escalated in a standard 3+3 fashion until a maximum tolerated dose is determined.

Pharmacokinetic Phase 1b (PK) Study Cohort; Phase II Cohort

pacritinib DRUG

For use in clinical studies as an oral agent, pacritinib is supplied as size #0 hard gelatin capsules with gray bodies and scarlet caps. Capsules contain 100 mg pacritinib (free base) and the following inactive ingredients: microcrystalline cellulose NF, polyethylene glycol 8000 NF, and magnesium stearate NF. The capsule gelatin is bovine derived. Pharmacies at investigational sites will receive subject-specific bottles containing 120 capsules packaged in 200 mL high-density polyethylene bottles with child-resistant closures.

Pharmacokinetic Phase 1b (PK) Study Cohort; Phase II Cohort

Eligibility Criteria

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

You may qualify if:

• Patients with histologically-or cytologically confirmed diagnosis of locally advanced and/or metastatic lung adenocarcinoma (Stage IV/AJCC Edition 8) (any PD-L1 status) without actionable driver mutations, who has failed at least one line of systemic treatment. Patients with locally advanced and/or metastatic lung adenocarcinoma with driver mutation who have failed standard targeted therapies can also be enrolled on this study.
• Be refractory to, or intolerant of, an established therapy known to provide clinical benefit for their condition. Patients can be eligible for study if they have failed at least one line of treatment.
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by the investigator. Evaluable disease in phase 1 is allowed.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 (AppendixH)
• Life expectancy of at least 3 months
• Be ≥18 years of age
• Negative pregnancy test (if female of childbearing potential)
• Adequate liver function:
• Total bilirubin \<1.5x upper limit of normal (ULN) (\<3xULN for subjects with liver metastases)
• Aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT), alkaline phosphatase \<2.5 x ULN.
• If liver metastases are present, then AST and ALT \<5 x ULN is allowed.
• Adequate renal function with calculated creatinine clearance ≥30 mL/min by Cockcroft-Gault Formula.
• Adequate hematologic status:
• Absolute neutrophil count ≥1500 cells/mm3
• Platelet count ≥100,000 (plt/mm3)

You may not qualify if:

• History of the following cardiac conditions:
• An acute ischemic cardiac event (e.g., myocardial infarction) or hospitalization for unstable angina within 3 months prior to first dose.
• Abnormal left ventricular ejection fraction on echocardiography (less than the lower limit of normal for a subject of that age at the treating institution or Grade 2 severity according to the New York Heart Association as defined by symptoms at less than ordinary levels of activity. Echo will only be considered for symptomatic patients with heart disease and concerns for heart failure. The Echo would be ordered by PI as standard of care.
• Uncontrolled cardiac disease, including unstable angina, uncontrolled hypertension (i.e., sustained systolic BP \>160 mmHg or diastolic BP \>90 mmHg), or need to change medication due to lack of disease control within 12 weeks prior to the provision of consent.
• History or presence of bradycardia (≤55 bpm) or history of symptomatic bradycardia, left bundle branch block, cardiac pacemaker or significant atrial tachyarrhythmias as defined by the need for treatment.
• Presence of any factors that increase the risk for QTc prolongation, e.g., resistant, or inadequately treated heart failure, presence of hypokalemia or hypomagnesemia not corrected by, or not responding to, replacement therapy or inadequately treated hypothyroidism as defined by the thyroid-stimulating hormone not within the expected range of the institution.
• Family history of long QTc syndrome or ventricular arrhythmias; personal history of long QTc syndrome or previous drug induced QTc prolongation of at least Grade 3 (QTc \>500 ms). (Appendix I)
• Have a corrected QT interval (QTcF, Fridericia's method) of \>450 msec in men and \>470 msec in women.
• Presence of symptomatic central nervous system metastatic disease that requires local therapy such as radiotherapy, surgery, or increasing dose of steroids within 2 weeks prior to Day 1 treatment.
• Have undergone major surgery, other than diagnostic surgery, within 2 weeks prior to Day 1
• Have active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
• Are pregnant or nursing.
• Received treatment with radiation therapy, chemotherapy, or investigational therapy within 28 days or 5 half-lives, whichever occurs first, prior to study entry.
• Are unwilling or unable to comply with procedures required in this protocol.
• Have known infection with human immunodeficiency virus, hepatitis B, or hepatitis C. Patients with history of chronic hepatitis that is not active are eligible.

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

MeSH Terms

Interventions

bemcentinib; 11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene

Central Study Contacts

Kayla Chamberlain

CONTACT

1-210-450-5964; chamberlink@uthscsa.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Phase 1b of the study will be conducted to establish the maximum tolerable dose, after pharmacokinetic samples from the first 10 subjects have been collected they will commence Cycle 1, Day 1 treatment. Phase 2 will then be enrolled in a single arm comparison study where some patients will be selected to undergo biopsy.

Study Record Dates

• First Submitted: July 9, 2024
• First Posted: July 24, 2024
• Study Start: December 27, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)