Solid Tumors
Conditions
Keywords
Neoplasms, Lung Neoplasms, Colorectal Neoplasms, Neuroendocrine Tumors, Pancreatic Neoplasms
Brief summary
DS-6051b is an orally administered inhibitor of the tyrosine kinases (ROS1) and neurotropic tyrosine kinase receptors (NTRK). This phase 1 first-in-human study evaluates safety and tolerability of DS-6051b in cancer subjects and identify a recommended phase 2 dose (RP2D). In addition, this study will also assess the pharmacokinetic (PK)/pharmacodynamic (PD) profiles and preliminary efficacy of DS-6051b.
Detailed description
The Dose Escalation part (Part 1) of this study will evaluate safety and tolerability, and determine the tentative RP2D. Plasma exposure of DS-6051a and the exposure - QT interval prolongation relationship will also be assessed. Approximately 30 subjects with advanced solid tumors harboring ROS1 or NTRK1, NTRK2, or NTRK3 rearrangement, neuroendocrine carcinoma, or with advanced solid tumors and tumor-induced pain will be enrolled. The Food Effect (FE) part of this study is to determine the effect of food on the PK of DS-6051a following administration of a single oral dose of DS-6051b. The safety and tolerability of DS-6051b administered with or without food will also be assessed. After the safety profile of DS-6051b is adequately evaluated, the Dose Expansion part (Part 2) will be initiated to further assess the safety and tolerability, and preliminarily evaluate the efficacy of DS-6051b at the tentative RP2D. Approximately 40 cancer subjects carrying a ROS1 or NTRK1, NTRK2, or NTRK3 rearrangement will be enrolled.
Interventions
DRUGDS6051b
DS-6051b 50 mg and 200 mg capsules for oral administration
Sponsors
AnHeart Therapeutics Inc.
Nuvation Bio Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically confirmed diagnosis of advanced solid tumors that have relapsed from or are refractory to standard treatment or for which no standard treatment is available 2. Part 1 Dose Escalation subjects must meet 1 of the following criteria: * Solid tumors with documented ROS1, NTRK1, NTRK2, or NTRK3 rearrangement * Neuroendocrine tumors * Solid tumors with tumor-induced pain 3. Part 2 Dose Expansion subjects must meet 1 of the following criteria: * NSCLC with documented ROS1, NTRK1, NTRK2, or NTRK3 rearrangement * k-RAS wild-type CRC with documented NTRK1, NTRK2, or NTRK3 rearrangement * Other solid tumors with documented ROS1, NTRK1, NTRK2, or NTRK3 rearrangement * Pulmonary LCNEC; 4. Male or female ≥18 years of age 5. Eastern Cooperative Oncology Group performance status 0 to 1 6. Adequate organ function 7. Adequate blood clotting function 8. Women of childbearing potential must have a negative pregnancy test 9. Willingness to provide archival tumor samples 10. Other inclusion criteria may apply
Exclusion criteria
1. Hematological malignancies 2. Known positive HIV infection, or active hepatitis B or C infection 3. Comorbidity that would interfere with therapy 4. Receipt of an allogeneic bone marrow or allogeneic stem cell transplant 5. Concomitant medical condition that would increase the risk of toxicity, in the opinion of the Investigator or Sponsor 6. History of myocardial infarction and unstable angina within 6 months before study drug treatment; symptomatic congestive heart failure (Congestive Heart Failure New York Heart Association Class III or IV); congenital long QT syndrome; or ventricular arrhythmias defined as grade ≥2 according to NCI CTCAE, v4 7. Clinically active primary central nervous system tumors or brain metastases with the exception of subjects with glioblastoma multiform that carry ROS1 rearrangement 8. Unresolved toxicities from previous anticancer therapy 9. Systemic treatment with anticancer therapy within 3 weeks before study drug treatment 10. Therapeutic radiation therapy or major surgery within 4 weeks before study drug treatment or palliative radiation therapy within 2 weeks before study drug treatment 11. Participation in a therapeutic clinical study within 3 weeks for biological treatments, and within 2 weeks or 5 half-lives, whichever is longer, for small molecule agents, before study drug treatment 12. Concomitant treatment with strong inhibitors or inducers of CYP3A4 and P-glycoprotein 13. Clinically significant malabsorption syndrome or other gastrointestinal disease that would impact drug absorption 14. QTcF values higher than 450 ms at screening 15. Breastfeeding 16. Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of participants with dose-limiting toxicities | within 21 days following the first dose of treatment | — |
| Tumor response | up to 2 years | Tumor response will be assessed using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum concentration (Cmax) for DS-6051a | At Days 1 and 15 of Cycle 1 (21 days) | — |
| Time to maximum concentration (Tmax) for DS-6051a | At Days 1 and 15 of Cycle 1 (21 days) | — |
| Area under the concentration-time curve from time zero to t (AUC0-t) for DS-6051a | At Days 1 and 15 of Cycle 1 (21 days) | — |
| Change from baseline in QTc interval | within 2 years | ECGs performed to assess QTc interval (ms) at baseline and on study treatment and at the end of treatment visit. |
Countries
United States
Outcome results
None listed