NBM-BMX for adults with metastatic uveal melanoma — dose-finding and safety
A Multicenter Phase Ib/II Study to Evaluate the Safety, Efficacy and Pharmacokinetics of NBM-BMX in Patients With Metastatic Uveal Melanoma
This study will test whether taking the oral drug NBM-BMX twice daily is safe, how the body handles it, and whether it can slow or shrink tumors in adults with metastatic uveal melanoma while finding the best dose.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 36 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Novelwise Pharmaceutical Corporation Industry-sponsored |
| Drugs / interventions | Chemotherapy, radiation |
| Locations | 3 sites (Scottsdale, Arizona and 2 other locations) |
| Trial ID | NCT07136181 on ClinicalTrials.gov |
What this trial studies
This Phase 1/2, open-label trial uses dose-escalation and expansion cohorts to identify a tolerable and potentially active dose of the oral agent NBM-BMX in adults with metastatic uveal melanoma. Participants take NBM-BMX capsules twice daily on an empty stomach with specific fasting rules, and undergo regular clinic visits for safety labs, pharmacokinetic sampling, and tumor assessments. Treatment continues until disease progression, unacceptable toxicity, or withdrawal, with a follow-up visit about 30 days after stopping. The study excludes prior HDAC inhibitor treatment and requires prior tebentafusp for HLA-A*02:01-positive patients unless deemed inappropriate.
Who should consider this trial
Good fit: Adults (≥18) with histologically or cytologically confirmed metastatic uveal melanoma, measurable disease by RECIST 1.1, ECOG 0–2, and who meet prior-therapy rules (no prior HDAC inhibitors; HLA-A*02:01-positive patients should have received tebentafusp unless inappropriate) are ideal candidates.
Not a fit: Patients with rapidly progressing disease, serious comorbidities, inability to follow strict fasting or medication restrictions (including avoiding acid-reducing agents), or prior HDAC inhibitor treatment may be unlikely to benefit from this study.
Why it matters
Potential benefit: If successful, NBM-BMX could provide an oral option that slows tumor growth or shrinks metastases and define a safe dose for further testing.
How similar studies have performed: This oral targeted approach is relatively novel for metastatic uveal melanoma; few systemic agents have produced durable responses historically, although tebentafusp showed survival benefit in a specific HLA subgroup.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
\- Patients must meet the following criteria to be eligible for study entry:
1. Signed, written IRB-approved informed consent.
2. Men and women age ≥ 18 years
3. ECOG Performance status ≤ 2
4. Have measurable disease based on RECIST 1.1
5. Histologic or cytologic confirmation of metastatic uveal melanoma
6. Previous Therapy
* Surgery: Previous surgery is permitted provided that a minimum of 28 days (4 weeks) has elapsed between any major surgery and date of registration, and that wound healing has occurred.
* Cytotoxic Chemotherapy: There is no limit to the number of prior regimens received.
* Other Systemic Therapy: There is no limit to the number of prior therapies received for metastatic uveal melanoma. Prior treatment with tebentafusp is required for HLA-A\*02:01-positive patients unless unavailable or clinically inappropriate, as determined by the investigator. Prior HDAC inhibitor treatment is not permitted.
Patients must have recovered (to baseline or ≤ grade 1) from all reversible toxicity related to prior chemotherapy or systemic therapy and have adequate washout as follows:
Longest of one of the following:
* Two weeks,
* 5 half-lives for investigational agents,
o For anti-cancer therapies with half-lives \> 8 days, a washout period of at least 28 days will be acceptable,
* Standard cycle length of standard therapies.
7. QTcF \<= 480 msec
8. Adequate hematopoietic capacity, as defined by the following:
* Hemoglobin ≥ 9.0 g/dL and not transfusion dependent
* Platelets ≥ 100,000/mm3
* Absolute neutrophil count ≥ 1,500 cells/mm3
9. Adequate hepatic function, as defined by the following:
* AST and ALT ≤ 2.5 times upper limit of normal (ULN) or ≤ 5 times ULN if liver metastases are present
* Total bilirubin ≤ 1.5 x ULN or within 3x the ULN for patients with Gilbert disease
* Albumin ≥ 3.0 g/dL
10. Adequate renal function, as defined by the following:
\- Renal: calculated creatinine clearance \>45 mL/min for patients between 18 and 70 years old with abnormal, increased, creatinine levels (Cockcroft-Gault formula; Appendix F). For patients who are greater than 70 years old, investigator judgment may be used to assess the renal risk of study participation.
11. Women/men of childbearing potential must have agreed to use two effective contraceptive methods while on study and for 6 months after the last dose of NBM-BMX.
12. Willingness and ability to comply with the study scheduled visits, treatment plans, laboratory tests and other procedures.
Exclusion Criteria:
Patients who meet the following criteria will be excluded from study entry:
1. Pregnant or nursing women. NOTE: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation and for at least 6 months after the last dose of NBM-BMX. Should a man father a child, or a woman become pregnant or suspect she is pregnant while participating in this study, he or she should inform the treating physician immediately.
2. Concurrent non-protocol-specified anti-tumor therapy (e.g., chemotherapy, other targeted therapy, radiation therapy, or photodynamic therapy)
3. History of other malignancies within 3 years of Day 1, except for tumors with a negligible risk for metastasis or death, such as adequately treated squamous-cell carcinoma of the skin, ductal carcinoma in situ of the breast, or carcinoma in situ of the cervix.
4. Active or uncontrolled infections or with serious illnesses or medical conditions which would not permit the patient to be managed according to the protocol.
5. History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or renders the patient at high risk from treatment complications.
6. Difficulty with swallowing oral medications.
7. Currently taking moderate and strong inhibitors (e.g., gemfibrozil) or inducers of CYP2C8.
8. A positive test for hepatitis B (HBsAg) and/or hepatitis C (anti-HCV antibody), unless the HBV DNA level and/or HCV RNA level is below the limit of detection.
9. Any of the following within 3 months of the first dose of NBM-BMX: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, or cerebrovascular accident including transient ischemic attack.
10. Current use or anticipated need for P-gp or BCRP inhibitors during the study period.
11. Use of proton pump inhibitors (PPIs), H2-receptor antagonists, or other systemic acid-reducing agents within 7 days prior to Cycle 1 Day 1 or planned use during the study treatment period, unless the patient can be switched to local antacids (e.g., calcium carbonate or aluminum hydroxide) taken at least 2 hours before or after NBM-BMX dosing.
Patients unable or unwilling to comply with this restriction should be excluded. Exceptions must be discussed with and approved by the Medical Monitor.
Where this trial is running
Scottsdale, Arizona and 2 other locations
- Honor Health Resarch Institute — Scottsdale, Arizona, United States (Recruiting)
- Sarah Cannon Research Institute (SCRI) - Denver HealthONE Location — Denver, Colorado, United States (Recruiting)
- SCRI Oncology Partners — Nashville, Tennessee, United States (Recruiting)
Study contacts
- Study coordinator: Annie Pai, PhD
- Email: NWP-US-info.tw@novelwisepharma.com
- Phone: 1 (910) 297-9045
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.