This is a multicenter, open-label, Phase 1 study of orally administered VMD-928 in adult
subjects with advanced solid tumors or lymphoma that have progressed or are non responsive to
available therapies and for which no standard or available curative therapy exists
Part-1 Escalation Phase [Key Inclusion]:
- Histologically or cytologically confirmed diagnosis of solid tumor malignancy or
lymphoma that is not responsive to standard therapies, are unfit for standard
chemotherapy or for which there is no approved or curative therapy.
- ECOG score of 0 or 1.
- Able to swallow and retain oral medication.
- Adequate organ system function.
Part-2 Expansion Phase [Key Inclusion]:
- Part-1 Escalation Phase inclusion criteria.
- (a) Thymic carcinoma, thymoma, pancreatic cancer, or breast cancer (TNBC); or (b) any
other cancer with histologically or cytologically or genomically confirmed diagnosis
of NTRK1 (TrkA) mutation, or fusion, or overexpression, translocation, amplification
or other alterations that may interfere with TrkA (NTRK1) signaling, as previously
identified with prior testing as routinely performed at Clinical Laboratory
Improvement Amendments (CLIA)-certified or other similarly-certified laboratories.
Part-3 Pharmacodynamic Activity (Eligible subjects in Part-2 may enroll in Part-3):
- Part-2 Expansion Phase inclusion criteria.
- Tumor with readily accessible lesion that is amenable to biopsy and consent to pre-and
Key Exclusion Criteria (Part-1, -2 and -3):
1. Received chemotherapy having delayed toxicity within the last 21 days (six weeks for
prior nitrosourea or mitomycin C).
2. Received anticancer therapy with radiation, immunotherapy, a biologic, surgery and/or
tumor embolization within the past 2 weeks.
3. Received an investigational anti-cancer drug within 21 days or 5 half-lives of the
investigational agent prior, whichever is shorter, to the first dose of VMD-928.
4. Unresolved toxicity from previous anti-cancer therapy ≥ CTCAE Grade 1 (except alopecia
or anemia) unless agreed to by both the Investigator and Sponsor.
5. Known active infections including HIV disease.
6. Currently pregnant, nursing, or planning to become pregnant during the course of the
7. QTcF interval ≥ 480 msec.
8. Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA)
functional classification system.
9. Acute coronary syndromes (including unstable angina), coronary angioplasty, or
stenting within the past 24 weeks.
10. Unstable or uncompensated respiratory, hepatic, renal, or cardiac disease that would
compromise the patient's safety or interfere with assessment of the drug.
11. Psychological, familial, sociological, geographical or other concurrent conditions
that would interfere with safety evaluation, limit the subject's ability to follow the
procedures in the protocol or otherwise jeopardize compliance with the protocol.
Subjects with uncontrolled major depression, bipolar disorder, or severe anxiety
disorder are excluded.
Key Exclusion Criteria (For Part-1 Escalation Phase only):
12. Any current medical condition that would alter the absorption, distribution,
metabolism or excretion of VMD-928 including but not limited to:
- Severe uncontrolled nausea or vomiting
- Severe uncontrolled diarrhea The intended population for VMD-928 are expected to
have had bowel resections and these subjects will be eligible for Part-1 Dose