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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04000529




Registration number
NCT04000529
Ethics application status
Date submitted
24/06/2019
Date registered
27/06/2019

Titles & IDs
Public title
Phase Ib Study of TNO155 in Combination With Spartalizumab or Ribociclib in Selected Malignancies
Scientific title
A Phase Ib, Open-label, Multi-center Study to Characterize the Safety, Tolerability, and Preliminary Efficacy of TNO155 in Combination With Spartalizumab or Ribociclib in Selected Malignancies
Secondary ID [1] 0 0
CTNO155B12101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-small Cell Lung Carcinoma 0 0
Head and Neck Squamous Cell Carcinoma 0 0
Esophageal SCC 0 0
Gastrointestinal Stromal Tumors 0 0
Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Head and neck
Cancer 0 0 0 0
Stomach
Cancer 0 0 0 0
Bowel - Small bowel (duodenum and ileum)
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Oesophageal (gullet)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - TNO155
Treatment: Drugs - Spartalizumab
Treatment: Drugs - Ribociclib

Experimental: TNO155 in combination with spartalizumab - TNO155 in combination with spartalizumab

Experimental: TNO155 in combination with ribociclib - TNO155 in combination with ribociclib


Treatment: Drugs: TNO155
Capsule

Treatment: Drugs: Spartalizumab
Concentrate for solution for infusion

Treatment: Drugs: Ribociclib
Capsule and tablet
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
DLT incidence
Timepoint [1] 0 0
1 year
Primary outcome [2] 0 0
AE and SAE incidence
Timepoint [2] 0 0
3 years
Primary outcome [3] 0 0
Dose interruptions, reductions and dose intensity, by treatment
Timepoint [3] 0 0
3 years
Secondary outcome [1] 0 0
Pharmacokinetics (PK): Cmax
Timepoint [1] 0 0
3 years
Secondary outcome [2] 0 0
Pharmacokinetics (PK): Tmax
Timepoint [2] 0 0
3 years
Secondary outcome [3] 0 0
Pharmacokinetics (PK): AUClast
Timepoint [3] 0 0
3 years
Secondary outcome [4] 0 0
Pharmacokinetics (PK): AUCtau
Timepoint [4] 0 0
3 years
Secondary outcome [5] 0 0
Efficacy measurements per RECIST v1.1: ORR
Timepoint [5] 0 0
3 years
Secondary outcome [6] 0 0
Efficacy measurements per RECIST v1.1: DCR
Timepoint [6] 0 0
3 years
Secondary outcome [7] 0 0
Efficacy measurements per RECIST v1.1: PFS
Timepoint [7] 0 0
3 years
Secondary outcome [8] 0 0
Efficacy measurements per RECIST v1.1: DOR
Timepoint [8] 0 0
3 years
Secondary outcome [9] 0 0
Efficacy measurements per iRECIST: ORR
Timepoint [9] 0 0
3 years
Secondary outcome [10] 0 0
Efficacy measurements per iRECIST: DCR
Timepoint [10] 0 0
3 years
Secondary outcome [11] 0 0
Efficacy measurements per iRECIST: PFS
Timepoint [11] 0 0
3 years
Secondary outcome [12] 0 0
Efficacy measurements per iRECIST: DOR
Timepoint [12] 0 0
3 years
Secondary outcome [13] 0 0
Overall Survival
Timepoint [13] 0 0
3 years

Eligibility
Key inclusion criteria
Key

1. Signed informed consent must be obtained prior to participation in the study.
2. Age = 18 years. For Japan only: written consent is necessary both from the patient and his/her legal representative if he/she is under the age of 20 years.
3. ECOG (Eastern Cooperative Oncology Group) performance status = 1.
4. Dose escalation part: Patients with advanced solid tumors, with evaluable disease as determined by RECIST version 1.1, and fit into one of the following groups:

a. For TNO155 plus spartalizumab combination: i. Advanced EGFR WT, ALK WT NSCLC, after progression on or intolerance to platinum-containing combination chemotherapy and after progression on anti-PD-1 or anti-PD-L1 therapy.

ii. Advanced HNSCC or esophageal SCC, after progression on or intolerance to platinum-containing combination chemotherapy.

iii. Advanced CRC, after progression on or intolerance to all standard-of-care (SOC) therapy per local guidelines.

b. For TNO155 plus ribociclib combination: Advanced solid malignancies with the exception of CRC or GIST, after progression on or intolerance to all SOC therapy per local guidelines. The exclusion of CRC applies only as of Protocol Amendment 4.
5. Dose expansion part: Patients with advanced solid tumors, with at least one measurable lesion as determined by RECIST version 1.1, who fit into one of the following groups:

a. For TNO155 plus spartalizumab combination: i. Advanced EGFR WT, ALK WT, KRAS G12C NSCLC after progression on or intolerance to platinum-containing combination chemotherapy and after progression on anti-PD-1 or anti-PD-L1 therapy.

ii. Advanced EGFR WT, ALK WT, KRAS WT NSCLC, after progression on or intolerance to platinum-containing combination chemotherapy and after progression on anti-PD-1 or anti-PD-L1 therapy.

iii. Advanced HNSCC, after progression on or intolerance to, platinum-containing combination chemotherapy.

b. For TNO155 plus ribociclib combination: i. Advanced EGFR WT, ALK WT, KRAS WT NSCLC, after progression on or intolerance to platinum-containing chemotherapy and anti-PD-1 or anti-PD-L1 therapy ii. Advanced HNSCC, after progression on or intolerance to all SOC per local guidelines
6. Patients with NSCLC whose tumors harbor genomic aberrations for which SOC targeted therapies exist and are locally approved and available must have had progression on or after, or intolerance to, the SOC targeted therapy/therapies as indicated
7. Patients must have a site of disease amenable to biopsy

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Prior treatment with a MAPK pathway inhibitor
2. Clinically significant cardiac disease or risk factors
3. Use of any agent known to prolong the QT interval unless it can be permanently discontinued for the duration of study (see list in Section 6.2.2).
4. History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO
5. Inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease) or impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drugs
6. Symptomatic CNS metastases which are neurologically unstable
7. Insufficient bone marrow function at screening:

1. Absolute Neutrophil Count (ANC) < 1.5 x 109/L.
2. Hemoglobin < 9.0 g/dL.
3. Platelets < 75 x 109/L for TNO155 plus spartalizumab combination; < 100 x 109/L for TNO155 plus ribociclib combination.
8. Insufficient hepatic or renal function at screening:

1. Serum total bilirubin > upper limit of normal (ULN) or, for TNO155 plus spartalizumab combination only, if liver metastases are present at baseline, serum total bilirubin > 1.5 x ULN. An exception for either combination is for patients with Gilbert's syndrome, who are excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN
2. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 x ULN for TNO155 plus spartalizumab combination or > 2.5 x ULN for TNO155 plus ribociclib combination, or > 5 x ULN for either combination if liver metastases are present.
3. Creatinine clearance < 60 mL/min (calculated using Cockcroft-Gault equation).
9. Pregnant or breast-feeding (lactating) women.

Additional exclusion criteria for the TNO155 plus spartalizumab combination
10. History of severe hypersensitivity reactions to other mAbs.
11. Active, known or suspected autoimmune disease.
12. History of or current interstitial lung disease or pneumonitis grade = 2.
13. Human Immunodeficiency Virus (HIV) infection, unless the patient is on antiviral therapy and has undetectable viral load.
14. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
15. Systemic chronic steroid therapy
16. Patients who discontinued prior anti-PD-1 therapy due to an anti-PD-1-related toxicity.

Additional exclusion criteria for the TNO155 plus ribociclib combination
17. Systolic Blood Pressure (SBP) < 90 mmHg.
18. International Normalized Ratio (INR) > 1.5 (unless the patient is receiving anticoagulants and the INR is within the therapeutic range of intended use for that anticoagulant within seven days prior to the first dose of study drug).
19. History of HIV infection (testing not mandatory)
20. Currently receiving any of the following substances and cannot be discontinued seven days prior to Cycle 1 Day 1:

* Concomitant medications or herbal supplements, that are strong inducers or inhibitors of CYP3A4/5,
* Medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5.
21. Previous treatment with a CDK4/6 inhibitor.
22. Patient is currently receiving or has received systemic corticosteroids = 2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment.

Note: The following uses of corticosteroids are permitted: single doses, topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular).

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/07/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
15/01/2024
Sample size
Target
Accrual to date
Final
122
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Novartis Investigative Site - Westmead
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Massachusetts
Country [2] 0 0
Belgium
State/province [2] 0 0
Bruxelles
Country [3] 0 0
China
State/province [3] 0 0
Sichuan
Country [4] 0 0
Germany
State/province [4] 0 0
Koeln
Country [5] 0 0
Hong Kong
State/province [5] 0 0
Hong Kong
Country [6] 0 0
Japan
State/province [6] 0 0
Tokyo
Country [7] 0 0
Singapore
State/province [7] 0 0
Singapore
Country [8] 0 0
Spain
State/province [8] 0 0
Catalunya
Country [9] 0 0
Spain
State/province [9] 0 0
Comunidad Valenciana

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04000529