An open-label, multi-center, phase I, dose finding study of oral TNO155 in adult patients with advanced solid tumors

Recruiting

• Conditions: Luncancer; 10027655; head- and neckcancer and other solid tumors

• Registration Number: NL-OMON54714
• Lead Sponsor: ovartis

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 33

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

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 < 50% (or below
institutional standard lower limit), uncontrolled hypertension, presence of
significant arrhythmias, QTcF > 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.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Adverse effects. DLTs, dose interruptions/reductions.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Overall response rate, disease control rate, duration of response, progression<br /><br>free survival, PK, changes from baseline of PD markers.</p><br>