Bemcentinib + Pacritinib for Lung Cancer

Overseen By Epp Goodwin

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: The University of Texas Health Science Center at San Antonio

Must not be taking: Anticonvulsants, Anticoagulants, CYP3A4 drugs, others

Disqualifiers: Cardiac conditions, CNS metastases, Infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

44 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking H2-receptor agonists (like cimetidine or ranitidine) and proton pump inhibitors (like omeprazole) at least seven days before starting the study treatment and throughout the study. If you are taking strong CYP3A4 inducers or inhibitors, you must stop them at least 5 half-lives before starting the treatment.

How is the drug combination of Bemcentinib and Pacritinib unique for lung cancer treatment?

The combination of Bemcentinib and Pacritinib for lung cancer is unique because it involves two drugs that target specific pathways in cancer cells, potentially offering a novel approach compared to traditional chemotherapy regimens. Bemcentinib is known to inhibit AXL, a protein that helps cancer cells survive and spread, while Pacritinib targets JAK2, a protein involved in cell growth, which may provide a different mechanism of action compared to existing treatments. ^{1 2 3 4 5}

What is the purpose of this trial?

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

Eligibility Criteria

Adults with advanced lung adenocarcinoma who've failed at least one systemic treatment can join. They must have measurable disease, good organ function, no serious heart conditions or infections, and be able to swallow pills. Women of childbearing potential need a negative pregnancy test and agree to use contraception.

Inclusion Criteria

Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by the investigator

Have no clinically significant abnormalities on urinalysis

Have acceptable coagulation status: Prothrombin time (PT) ≤ 1.5 x ULN, Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN

Exclusion Criteria

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, Uncontrolled cardiac disease, History or presence of bradycardia, Presence of any factors that increase the risk for QTc prolongation, Family history of long QTc syndrome or ventricular arrhythmias, Personal history of long QTc syndrome or previous drug induced QTc prolongation

I do not have any serious infections that need treatment with medication.

I can stop taking my acid reflux medication 7 days before starting the study treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase Ib Treatment

Participants receive bemcentinib and pacritinib in combination to determine the maximum tolerated dose (MTD) using a Bayesian Optimal Interval (BOIN) design

4 weeks

Multiple visits for PK sampling on Days 1, 2, 7, 8, 14, and 22

Phase II Treatment

Participants receive the maximum tolerated dose of bemcentinib and pacritinib, with up to 15 participants undergoing a biopsy

Up to 48 months

Follow-up

Participants are monitored for progression-free survival and overall survival

Up to 48 months

Treatment Details

Interventions

• Bemcentinib
• Pacritinib

Trial Overview The trial is testing the combination of two drugs, Bemcentinib and Pacritinib, for treating advanced lung adenocarcinoma. It's an early-phase study assessing dosage safety, how the body processes the drugs (pharmacokinetics), their effects on cancer (pharmacodynamics), and effectiveness.

Participant Groups

Group I: Phase II Cohort Experimental Treatment 2 Interventions

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.

Group II: Pharmacokinetic Phase 1b (PK) Study Cohort Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

The University of Texas Health Science Center at San Antonio

Lead Sponsor

Trials

486

Recruited

92,500+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 17 previously treated patients with non-small cell lung carcinoma (NSCLC), the combination therapy of carboplatin-paclitaxel plus bevacizumab (TC+Bev) showed an objective response rate of 17.6% and a disease control rate of 70.6%, indicating its potential efficacy as a second-line treatment.

The treatment was well-tolerated with no treatment-related deaths reported, and the median progression-free survival was 4.7 months, suggesting that TC+Bev has an acceptable safety profile for patients with NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of chemotherapy with carboplatin-paclitaxel plus bevacizumab for previously treated patients with advanced non-small cell carcinoma]. Maki, S., Igawa, S., Otani, S., et al.[2015]

In a study involving 939 patients with advanced nonsquamous non-small-cell lung cancer, the combination of pemetrexed, carboplatin, and bevacizumab (PemCBev) did not show a significant improvement in overall survival compared to paclitaxel, carboplatin, and bevacizumab (PacCBev), with median overall survival times of 12.6 and 13.4 months, respectively.

However, PemCBev demonstrated a significantly better progression-free survival (6.0 months vs. 5.6 months) and had a different toxicity profile, with more cases of anemia and thrombocytopenia, while PacCBev was associated with higher rates of neutropenia and alopecia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PointBreak: a randomized phase III study of pemetrexed plus carboplatin and bevacizumab followed by maintenance pemetrexed and bevacizumab versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer. Patel, JD., Socinski, MA., Garon, EB., et al.[2022]

In a study of 1,534 patients with advanced non-squamous non-small cell lung cancer, the combination of platinum/paclitaxel/bevacizumab resulted in a significantly higher overall response rate (ORR) of 40.8% compared to 32.7% for platinum/pemetrexed.

Despite the better ORR with the paclitaxel/bevacizumab regimen, there was no significant difference in progression-free survival (PFS) or overall survival (OS) between the two treatment groups, suggesting that both regimens are similarly effective and should be chosen based on side effect profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Chemotherapeutic Regimens Frequently Used in Metastatic Non-squamous NSCLC Treatment. Krejci, D., Opalka, P., Krejci, J., et al.[2021]

In a study involving 361 patients with advanced nonsquamous non-small-cell lung cancer, the combination of pemetrexed and carboplatin (Pem+Cb) did not show a significant advantage in progression-free survival without grade 4 toxicity compared to paclitaxel, carboplatin, and bevacizumab (Pac+Cb+Bev).

While both treatment regimens were generally well tolerated, Pem+Cb was associated with higher rates of grade 3/4 anemia and thrombocytopenia, whereas Pac+Cb+Bev had more cases of grade 3/4 neutropenia and alopecia, indicating differing toxicity profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PRONOUNCE: randomized, open-label, phase III study of first-line pemetrexed + carboplatin followed by maintenance pemetrexed versus paclitaxel + carboplatin + bevacizumab followed by maintenance bevacizumab in patients ith advanced nonsquamous non-small-cell lung cancer. Zinner, RG., Obasaju, CK., Spigel, DR., et al.[2022]

In a retrospective analysis of 48 patients with non-squamous non-small cell lung cancer (NSCLC), the combination of bevacizumab (Bev) with carboplatin and nab-paclitaxel showed a high response rate of 56.3% and a disease control rate of 79.2%.

The treatment resulted in median progression-free and overall survival times of 6.8 and 10.4 months, respectively, with manageable toxicities, although some patients experienced significant adverse events like grade 3 neutropenia and one case of grade 5 toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab Plus Carboplatin Plus Nab-paclitaxel for Non-squamous Non-small Cell Lung Cancer in a Real-world Setting. Tamiya, A., Tamiya, M., Inagaki, Y., et al.[2023]

References

1. Japan pubmed.ncbi.nlm.nih.gov

[Efficacy of chemotherapy with carboplatin-paclitaxel plus bevacizumab for previously treated patients with advanced non-small cell carcinoma]. [2015]

2. United States pubmed.ncbi.nlm.nih.gov

PointBreak: a randomized phase III study of pemetrexed plus carboplatin and bevacizumab followed by maintenance pemetrexed and bevacizumab versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer. [2022]

3. Greece pubmed.ncbi.nlm.nih.gov

Comparison of Chemotherapeutic Regimens Frequently Used in Metastatic Non-squamous NSCLC Treatment. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

PRONOUNCE: randomized, open-label, phase III study of first-line pemetrexed + carboplatin followed by maintenance pemetrexed versus paclitaxel + carboplatin + bevacizumab followed by maintenance bevacizumab in patients ith advanced nonsquamous non-small-cell lung cancer. [2022]

5. Greece pubmed.ncbi.nlm.nih.gov

Bevacizumab Plus Carboplatin Plus Nab-paclitaxel for Non-squamous Non-small Cell Lung Cancer in a Real-world Setting. [2023]