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| ID | Type | Description | Link |
|---|---|---|---|
| 2023-508925-29-00 | Other Identifier | EU CTIS |
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Business reasons and not due to any safety concerns
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The purpose of this first in human (FIH) trial was to characterize the safety and tolerability of the SHP2 inhibitor TNO155 alone and in combination with EGF816 (nazartinib) and identify a recommended dose for future studies in adult patients with advanced solid tumors in selected indications.
This study has been designed as a Phase I, open-label, dose finding study with a dose escalation part and a dose expansion part in adult patients with selected advanced solid tumors. The study treatment, TNO155 alone or in combination with EGF816 (nazartinib), was taken until the patient experienced unacceptable toxicity, progressive disease and/or treatment was discontinued at the discretion of the investigator or the patient or due to withdrawal of consent.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TNO155 | Experimental | TNO155 for oral administration |
|
| TNO155 in combination with EGF816 (nazartinib) | Experimental | TNO155 in combination with EGF816 (nazartinib) in patients with advanced EGFR mutant NSCLC |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TNO155 | Drug | TNO155 for oral administration |
| |
| TNO155 in combination with EGF816 (nazartinib) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with adverse events and serious adverse events | All patients participating in this study will be assessed for incidence and severity of adverse events (AEs) and serious AEs, including changes in laboratory values, vital signs, electrocardiograms and cardiac biomarkers | up to 5 years; at least once per treatment cycle |
| Number of participants with dose limiting toxicities | Incidence and nature of dose limiting toxicities (DLTs) in the dose escalation part. A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first treatment cycle (either 21 days or 28 days, depending on the cohort's treatment schedule) with TNO155 or with TNO155 in combination with EGF816 (nazartinib) | up to 28-day cycle |
| Number of participants with dose interruptions and reductions | Assessment of tolerability. For patients who do not tolerate the protocol-specified dosing schedule, dose adjustments may be permitted in order to allow patients to continue the study treatment | Up to 5 years |
| Dose intensity of study drugs | Dose intensity is computed as the ratio of actual cumulative dose received to actual duration of exposure | Up to 5 years |
| Measure | Description | Time Frame |
|---|---|---|
| Overall response rate (ORR) per RECIST v1.1 | ORR is the proportion of patients with a best overall response of Complete Response (CR) or Partial response (PR) | From start of treatment for 60 months |
| Disease control rate (DCR) per RECIST v1.1 |
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Inclusion Criteria:
Able to understand and voluntarily sign the ICF and able to comply with the study visit schedule and the other protocol requirements.
Patient (male or female) ≥18 years of age willing to agree to not father a child/become pregnant and comply with effective contraception criteria.
Must have progressed following standard therapy, or for whom, in the opinion of the Investigator, no effective standard therapy exists, is tolerated or is appropriate.
ECOG (Eastern cooperative oncology group) performance status ≤2
Additional criteria only appying to TNO155 in combination with EGF816 (nazartinib):
Patients must be screened for Hepatitis B virus and Hepatitis C virus
Exclusion Criteria:
Tumors harboring known activating KRAS, NRAS, HRAS, BRAF or PTPN11 (SHP2) mutations. (Exceptions are KRAS G12-mutant NSCLC's)
History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
Any medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.
Clinically significant cardiac disease.
Active diarrhea or inflammatory bowel disease
Insufficient bone marrow function
Insufficient hepatic and renal function.
Additional criteria only appying to TNO155 in combination with EGF816 (nazartinib):
Patients with a known history of human immunodeficiency virus (HIV) seropositivity.
Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use at the time of study entry.
Patients who have undergone a bone marrow or solid organ transplant
Patients with a history or presence of interstitial lung disease or interstitial pneumonitis
Bullous and exfoliative skin disorders at screening of any grade
Presence of clinically significant ophthalmological abnormalities that might increase the risk of corneal epithelial injury
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| H Lee Moffitt Cancer Center and Research Institute | Tampa | Florida | 33612 | United States | ||
| Dana Farber Cancer Center |
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| Label | URL |
|---|---|
| CTNO155X2101 Clinical Trial Results Summary | View source |
| A Plain Language Trial Summary is available on www.novctrd.com | View source |
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| Drug |
TNO155 for oral administration; EGF816 (nazartinib) for oral administration |
|
DCR is the proportion of patients with a best overall response of CR or PR or stable disease (SD)
| From start of treatment for 60 months |
| Progression-free survival (PFS) per RECIST v1.1 | PFS is the time from date start of treatment to the date of event defined as the first documented progression or death due to any cause | Up to 5 years |
| Duration of response (DOR) per RECIST v1.1 | DOR is the time from first documented response (PR or CR) to the date of first documented disease progression or death due to any cause | Up to 5 years |
| Change from baseline in DUSP6 in tumor samples | Dual Specificity Phosphatase 6 (DUSP6) mRNA levels assessed in paired tumor biopsy samples by quantitative polymerase chain reaction (qPCR) | At screening and between Cycle 1 and Cycle 3. One cycle=either 21 days or 28 days, depending on the cohort's treatment schedule. |
| Area under the plasma concentration-time curve (AUC) of study drugs | Pharmacokinetic (PK) parameters calculated based on the plasma concentrations versus time profiles by using non-compartmental methods | From pre-dose up to 48 hours post-dose on Cycle 1 Day 1 and from pre-dose up to 24 hours post-dose on Cycle 1 Day 14. One cycle=21 days or 28 days, depending on the dosing schedule. |
| Peak plasma concentration (Cmax) of study drugs | PK parameters calculated based on the plasma concentrations versus time profiles by using non-compartmental methods | From pre-dose up to 48 hours post-dose on Cycle 1 Day 1 and from pre-dose up to 24 hours post-dose on Cycle 1 Day 14. One cycle=21 days or 28 days, depending on the dosing schedule. |
| Time to reach peak plasma concentration (Tmax) of study drugs | PK parameters calculated based on the plasma concentrations versus time profiles by using non-compartmental methods | From pre-dose up to 48 hours post-dose on Cycle 1 Day 1 and from pre-dose up to 24 hours post-dose on Cycle 1 Day 14. One cycle=21 days or 28 days, depending on the dosing schedule. |
| Apparent terminal elimination half-life of study drugs | PK parameters calculated based on the plasma concentrations versus time profiles by using non-compartmental methods | From pre-dose up to 48 hours post-dose on Cycle 1 Day 1 and from pre-dose up to 24 hours post-dose on Cycle 1 Day 14. One cycle=21 days or 28 days, depending on the dosing schedule. |
| Boston |
| Massachusetts |
| 02215 |
| United States |
| Memorial Sloane Ketterin Cancer Ctr | New York | New York | 10065 | United States |
| Sarah Cannon Research Institute | Nashville | Tennessee | 37221 | United States |
| Novartis Investigative Site | Toronto | Ontario | M5G 2M9 | Canada |
| Novartis Investigative Site | Milan | MI | 20141 | Italy |
| Novartis Investigative Site | Kobe | 650-0017 | Japan |
| Novartis Investigative Site | Rotterdam | South Holland | 3015 GD | Netherlands |
| Novartis Investigative Site | Amsterdam | 1066 CX | Netherlands |
| Novartis Investigative Site | Singapore | 168583 | Singapore |
| Novartis Investigative Site | Seoul | 03080 | South Korea |
| Novartis Investigative Site | Seoul | 05505 | South Korea |
| Novartis Investigative Site | L'Hospitalet de Llobregat | Barcelona | 08907 | Spain |
| Novartis Investigative Site | Barcelona | Catalonia | 08035 | Spain |
| Novartis Investigative Site | Madrid | 28009 | Spain |
| Novartis Investigative Site | Madrid | 28034 | Spain |
| Novartis Investigative Site | Madrid | 28040 | Spain |
| Novartis Investigative Site | Taipei | 10002 | Taiwan |
| ID | Term |
|---|---|
| D000077277 | Esophageal Squamous Cell Carcinoma |
| D008545 | Melanoma |
| D000077195 | Squamous Cell Carcinoma of Head and Neck |
| D009634 | Noonan Syndrome |
| ID | Term |
|---|---|
| D002294 | Carcinoma, Squamous Cell |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D018307 | Neoplasms, Squamous Cell |
| D004938 | Esophageal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D006258 | Head and Neck Neoplasms |
| D004066 | Digestive System Diseases |
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D019465 | Craniofacial Abnormalities |
| D009139 | Musculoskeletal Abnormalities |
| D009140 | Musculoskeletal Diseases |
| D006330 | Heart Defects, Congenital |
| D018376 | Cardiovascular Abnormalities |
| D002318 | Cardiovascular Diseases |
| D006331 | Heart Diseases |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D003240 | Connective Tissue Diseases |
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| ID | Term |
|---|---|
| C000619734 | nazartinib |
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