head- and neckcancer and other solid tumors Luncancer
Conditions
Interventions
Treatment with oral TNO155 monotherapy or nazartinib in combination with
TNO155. Several dosing schedule will be examined.
Sponsors
Novartis
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. >=18 years of age. 2. Site of disease amenable to biopsy. 3. ECOG performance status 0, 1, 2. 4. Presence of at least one measurable lesion (RECIST v1.1). 5. Dose escalation part: • Advanced NSCLC (harbouring an activating EGFR mutation), advanced HNSCC, advanced GIST,KRASG12C mutant NSCLC, advanced oesophagol SCC and NRAS/BRAF WT melanoma who progressed after Standard of Care (SoC) or for whom no effective therapy exists) See protocol page 49 for details. 6. Dose expansion part: • Group 1: advanced RAS/BRAF wild type NSCLC. • Group 2: advanced RAS/BRAF wild type HNSCC. • Group 3: advanced RAS/BRAF wild type other malignancies with RTK-dependency. Patients with NSCLC or HNSCC must have progressed on or after (or intolerant to), platinum-containing combination therapy. • Group 4: advanced RAS/BRAF WT other solid malignancy (excl CRC), after progression on standard of care. Patients with NSCLC or HNSCC must have progressed on or after (or intolerant to), platinum-containing combination therapy. For the first 4 groups the requirement for HRAS mutation testing may be waived following documented discussion with Novartis when local testing for HRAS mutations is not feasible. Group 5: Advanced KRAS G12C-mutant NSCLC, after progression on or after, or intolerance to SOC, Group 6: advanced NRAS/BRAF WT melanoma, after progression on or after or intolerance to SOC immuno-oncologic therapy. See protocol page 49-50 for more details.
Exclusion criteria
Exclusion criteria: 1. Tumors harbouring known activating KRAS, NRAS, HRAS, BRAF, or PTPN11 (SHP2) mutations, with the exception of KRAS G12C-mutant CRC in dose escalation and KRAS G12C-mutant NSCLC in dose expansion. 2. Prior and concomitant anti-cancer therapies as radiotherapy, surgery, immunotherapy, cytotoxic agents, chemotherapy within half-live timelines as described in protocol page 38. 2A. No resolution of all clinically significant toxicity on prior systemicanti- cancer therapy (except where otherwise stated in the protocol and alopecia). 2B. Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers; 3. History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO. 4. Ongoing active diarrhoea requiring medication. 5. All primary central nervous system (CNS) tumors or symptomatic CNS metastases which are neurologically unstable or requiring increasing doses of steroids within the 4 weeks prior to study entry. See protocol page 38-39 for more details. 6. Clinically significant cardiac disease e.g. LVEF 450 msec for males and >460 msec for females - See protocol page 39 for details. 7. Treatment with prohibited medication. See protocol appendix 2 for details. . 8. Insufficient bone marrow function, liver and kidney function defined by lab values. See protocol page 39 and 40 for details 9. The following labvalues must be within the lab normal ranges of the institution (and cannot be corrected with supplements): Potassium - magnesium - phosphorus - total calcium - fasting glucose 10. Pregnancy, lactation, insufficient contraception for females of childbearing potential. Males not using a condom. 11. Use of any live or live attenuated vaccines against infectious diseases within 4 weeks prior to study treatment initiation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse effects. DLTs, dose interruptions/reductions. | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall response rate, disease control rate, duration of response, progression free survival, PK, changes from baseline of PD markers. | — |
Countries
Netherlands
Outcome results
None listed