NCT04000529

Brief Summary

This study was a Phase Ib, multi-center, open-label study of TNO155 in combination with spartalizumab or ribociclib with a dose escalation part followed by a dose expansion part in adult subjects with advanced solid tumors. These two treatment arms enrolled subjects in parallel to characterize the safety, tolerability, PK, PD and preliminary antitumor activity. The study treatment was administered until the subject experienced unacceptable toxicity, progressive disease, and/or had treatment discontinued at the discretion of the Investigator or the subject, or due to withdrawal of consent.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
122

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Jul 2019

Longer than P75 for phase_1

Geographic Reach
9 countries

10 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 24, 2019

Completed
3 days until next milestone

First Posted

Study publicly available on registry

June 27, 2019

Completed
1 month until next milestone

Study Start

First participant enrolled

July 30, 2019

Completed
4.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 15, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 15, 2024

Completed
Last Updated

September 30, 2025

Status Verified

September 1, 2025

Enrollment Period

4.5 years

First QC Date

June 24, 2019

Last Update Submit

September 24, 2025

Conditions

Non-small Cell Lung CarcinomaHead and Neck Squamous Cell CarcinomaEsophageal SCCGastrointestinal Stromal TumorsColorectal Cancer

Keywords

TNO155, spartalizumab, ribociclib, checkpoint inhibitor, SHP2, PD-1, CDK4/6, NSCLC, CRC, HNSCC, KRAS, esophageal SCC, GIST

Outcome Measures

Primary Outcomes (3)

  • DLT incidence

    Incidence of dose limiting toxicities (DLTs) during the first cycle of combination treatment during the dose escalation part

    1 year

  • AE and SAE incidence

    Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) as per CTCAE v5.0, by treatment

    3 years

  • Dose interruptions, reductions and dose intensity, by treatment

    Dose tolerability

    3 years

Secondary Outcomes (13)

  • Pharmacokinetics (PK): Cmax

    3 years

  • Pharmacokinetics (PK): Tmax

    3 years

  • Pharmacokinetics (PK): AUClast

    3 years

  • Pharmacokinetics (PK): AUCtau

    3 years

  • Efficacy measurements per RECIST v1.1: ORR

    3 years

  • +8 more secondary outcomes

Study Arms (2)

TNO155 in combination with spartalizumab

EXPERIMENTAL

TNO155 in combination with spartalizumab

Drug: TNO155Drug: Spartalizumab

TNO155 in combination with ribociclib

EXPERIMENTAL

TNO155 in combination with ribociclib

Drug: TNO155Drug: Ribociclib

Interventions

TNO155DRUG

Capsule

TNO155 in combination with ribociclibTNO155 in combination with spartalizumab
SpartalizumabDRUG

Concentrate for solution for infusion

Also known as: PDR001
TNO155 in combination with spartalizumab
RibociclibDRUG

Capsule and tablet

Also known as: LEE011
TNO155 in combination with ribociclib

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Signed informed consent must be obtained prior to participation in the study.
  • 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.
  • ECOG (Eastern Cooperative Oncology Group) performance status ≤ 1.
  • 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.
  • 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
  • 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
  • Patients must have a site of disease amenable to biopsy

You may not qualify if:

  • Prior treatment with a MAPK pathway inhibitor
  • Clinically significant cardiac disease or risk factors
  • 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).
  • History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO
  • 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
  • Symptomatic CNS metastases which are neurologically unstable
  • Insufficient bone marrow function at screening:
  • Absolute Neutrophil Count (ANC) \< 1.5 x 109/L.
  • Hemoglobin \< 9.0 g/dL.
  • Platelets \< 75 x 109/L for TNO155 plus spartalizumab combination; \< 100 x 109/L for TNO155 plus ribociclib combination.
  • Insufficient hepatic or renal function at screening:
  • 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
  • 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.
  • Creatinine clearance \< 60 mL/min (calculated using Cockcroft-Gault equation).
  • Pregnant or breast-feeding (lactating) women.
  • +16 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Novartis Investigative Site

Westmead, New South Wales, 2145, Australia

Location

Novartis Investigative Site

Brussels, 1200, Belgium

Location

Novartis Investigative Site

Chengdu, Sichuan, 610041, China

Location

Novartis Investigative Site

Cologne, 50937, Germany

Location

Novartis Investigative Site

Hong Kong, Hong Kong

Location

Novartis Investigative Site

Chuo Ku, Tokyo, 104 0045, Japan

Location

Novartis Investigative Site

Singapore, 119228, Singapore

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Valencia, Valencia, 46010, Spain

Location

Related Publications (1)

  • Chen H, Cresswell GM, Libring S, Ayers MG, Miao J, Zhang ZY, Solorio L, Ratliff TL, Wendt MK. Tumor Cell-Autonomous SHP2 Contributes to Immune Suppression in Metastatic Breast Cancer. Cancer Res Commun. 2022 Oct 3;2(10):1104-1118. doi: 10.1158/2767-9764.CRC-22-0117. eCollection 2022 Oct.

    PMID: 36969745DERIVED

Related Links

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell LungSquamous Cell Carcinoma of Head and NeckEsophageal Squamous Cell CarcinomaGastrointestinal Stromal TumorsColorectal NeoplasmsParkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

spartalizumabribociclib

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract DiseasesCarcinoma, Squamous CellCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeHead and Neck NeoplasmsNeoplasms, Squamous CellEsophageal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsDigestive System DiseasesEsophageal DiseasesGastrointestinal DiseasesNeoplasms, Connective TissueNeoplasms, Connective and Soft TissueIntestinal NeoplasmsColonic DiseasesIntestinal DiseasesRectal Diseases

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 24, 2019

First Posted

June 27, 2019

Study Start

July 30, 2019

Primary Completion

January 15, 2024

Study Completion

January 15, 2024

Last Updated

September 30, 2025

Record last verified: 2025-09

Data Sharing

IPD Sharing
Will not share

Locations

SG(1)AU(1)JP(1)DE(1)BE(1)HK(1)CN(1)ES(2)US(1)