batoprotafib (TNO155) / Novartis - LARVOL DELTA

Harnessing SHP2-targeted signaling to reinforce anti-tumor immune responses (AACR 2026) - "These findings demonstrate that SHP2 inhibition enhances anti-tumor immune responses and supports its potential as a dual-function therapeutic strategy in cancer immunotherapy. This study provides a robust preclinical foundation for the translational development of SHP2-targeted approaches in precision oncology."

IO biomarker • Oncology • CD69 • CD8 • GZMB • HAVCR2 • IFNG • LAG3 • PD-L1

KontRASt-01: Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation (clinicaltrials.gov) - P1/2 | N=344 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Aug 2026 ➔ Jan 2027 | Trial primary completion date: Aug 2026 ➔ Jan 2027

Trial completion date • Trial primary completion date • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

KontRASt-R: Rollover Study for Participants Who Have Been Treated With and Are Continuing to Benefit From Opnurasib as a Single Agent or in Combination With Other Study Treatments (clinicaltrials.gov) - P1/2 | N=40 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

New P1/2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Dose Finding Study of TNO155 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=255 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Apr 2024 ➔ Aug 2024 | Trial primary completion date: Feb 2024 ➔ Aug 2024

First-in-human • Trial completion date • Trial primary completion date • Cutaneous Melanoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Stromal Tumor • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • DUSP6 • KRAS

Dose Finding Study of TNO155 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=255 | Recruiting | Sponsor: Novartis Pharmaceuticals | N=135 ➔ 255

Enrollment change • First-in-human • Cutaneous Melanoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Stromal Tumor • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Thoracic Cancer • DUSP6 • KRAS

Dose Finding Study of TNO155 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=135 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Aug 2021 ➔ Aug 2022 | Trial primary completion date: Aug 2021 ➔ Aug 2022

First-in-human • Trial completion date • Trial primary completion date • Cutaneous Melanoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Stromal Tumor • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Thoracic Cancer • DUSP6 • KRAS

Dose Finding Study of TNO155 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=255 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Oct 2024 ➔ Apr 2025 | Trial primary completion date: Oct 2024 ➔ Apr 2025

First-in-human • Trial completion date • Trial primary completion date • Cutaneous Melanoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Stromal Tumor • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • DUSP6 • KRAS

Dose Finding Study of TNO155 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=105 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • First-in-human • Cutaneous Melanoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Stromal Tumor • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • DUSP6 • KRAS

Dose Finding Study of TNO155 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=227 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: May 2025 ➔ Nov 2025 | Trial primary completion date: May 2025 ➔ Nov 2025

First-in-human • Trial completion date • Trial primary completion date • Cutaneous Melanoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Stromal Tumor • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • DUSP6 • KRAS

Dose Finding Study of TNO155 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=135 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Aug 2020 ➔ Aug 2021 | Trial primary completion date: Aug 2020 ➔ Aug 2021

First-in-human • Trial completion date • Trial primary completion date • Cutaneous Melanoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Stromal Tumor • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Thoracic Cancer • DUSP6 • KRAS

Dose Finding Study of TNO155 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=135 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Mar 2019 ➔ Aug 2020 | Trial primary completion date: Mar 2019 ➔ Aug 2020

First-in-human • Trial completion date • Trial primary completion date • Cutaneous Melanoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Stromal Tumor • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Thoracic Cancer • DUSP6 • KRAS

Dose Finding Study of TNO155 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=227 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial primary completion date: Nov 2025 ➔ Jul 2025 | Trial completion date: Nov 2025 ➔ Jul 2025

First-in-human • Trial completion date • Trial primary completion date • Cutaneous Melanoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Stromal Tumor • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • DUSP6 • KRAS

Dose Finding Study of TNO155 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=227 | Terminated | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Terminated; Business reasons and not due to any safety concerns

First-in-human • Trial termination • Cutaneous Melanoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Stromal Tumor • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • DUSP6 • KRAS

Dose Finding Study of TNO155 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=255 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Aug 2022 ➔ Aug 2023 | Trial primary completion date: Aug 2022 ➔ Aug 2023

First-in-human • Trial completion date • Trial primary completion date • Cutaneous Melanoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Stromal Tumor • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • DUSP6 • KRAS

Dose Finding Study of TNO155 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=227 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • First-in-human • Cutaneous Melanoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Stromal Tumor • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • DUSP6 • KRAS

Dose Finding Study of TNO155 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=135 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Mar 2020 ➔ Mar 2019 | Trial primary completion date: Mar 2020 ➔ Mar 2019

First-in-human • Trial completion date • Trial primary completion date • Cutaneous Melanoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Stromal Tumor • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • DUSP6 • KRAS

Dose Finding Study of TNO155 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=255 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Aug 2023 ➔ Feb 2024 | Trial primary completion date: Aug 2023 ➔ Feb 2024

First-in-human • Trial completion date • Trial primary completion date • Cutaneous Melanoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Stromal Tumor • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • DUSP6 • KRAS

Dose Finding Study of TNO155 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=105 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

First-in-human • Cutaneous Melanoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Stromal Tumor • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • DUSP6 • KRAS

Combination therapy with lorlatinib and mitogen-activated protein kinase pathway inhibition in previously treated ALK- or ROS1-rearranged lung cancer. (PubMed, Lung Cancer) - "Regimens co-targeting the MAPK pathway and ALK or ROS1 had limited efficacy in unselected patients with lorlatinib-resistant NSCLC, underscoring the need for more effective and biomarker-informed treatment strategies."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Respiratory Diseases • Retinal Disorders • Solid Tumor • ALK • ROS1

KontRASt-01 update: Safety and efficacy of JDQ443 in KRAS G12C-mutated solid tumors including non-small cell lung cancer (NSCLC). (ASCO 2023) - P1/2 | "JDQ443 demonstrates an acceptable safety and tolerability profile at 200 mg BID, with clinical activity in pts with NSCLC. Enrollment is ongoing to the JDQ443 monotherapy DEx and the JDQ443 + TNO155 and JDQ443 + tislelizumab combination arms. Clinical trial information: NCT04699188."

Clinical • IO biomarker • Colorectal Cancer • Fatigue • Gastrointestinal Cancer • Hematological Disorders • Lung Cancer • Musculoskeletal Pain • Neutropenia • Non Small Cell Lung Cancer • Oncology • Pain • Solid Tumor • KRAS

KontRASt-01: Preliminary Safety and Efficacy of JDQ443 + TNO155 in Patients with Advanced, KRAS G12C-Mutated Solid Tumors (IASLC-WCLC 2023) - P1/2 | "JDQ443+TNO155 was tolerated with notable toxicities of edema, cytopenias, and fatigue. MTD was not reached; the RD for further evaluation was selected based on collective safety, pharmacokinetics, and efficacy. Preliminary anti-tumor activity was observed, including in KRASG12C inhibitor previously-treated NSCLC."

Clinical • Metastases • Anemia • Fatigue • Hematological Disorders • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Thrombocytopenia • KRAS

PD-1 Expression in Lymphoma Cells Mediates Cellular Proliferation By Engaging Phosphatase SHP-1/SHP-2 (ASH 2023) - "Our group showed a selective response (~40%) with the PD-1 blocking antibody pembrolizumab in patients with RT, particularly after prior exposure to ibrutinib (Ding et al, Blood, 2017)...SHP-1 (TPI-1) and SHP-1+SHP-2 (TPI-1+TNO155) inhibitor treatment promoted OCI-LY19 cell death and led to recovery of phosphorylation on ATM, Chk-2 and p53 in these cells... Our data showed robust PD-1 expression in patients with Richter transformation from CLL to DLBCL. PD-1 overexpression in DLBCL lymphoma cell lines enhanced cell proliferation in vitro and in vivo. Further investigation identified that PD-1 modified the phosphorylation/function of SHP phosphatases and thereby regulated p53 pathways (Figure 1)."

IO biomarker • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • CHEK2 • LY9 • NAT10 • PD-1 • PD-L1 • PD-L2

A phase 1b, multicenter, open-label dose-escalation and expansion platform study of select drug combinations in adult patients with advanced or metastatic BRAF V600 colorectal cancer (AACR-NCI-EORTC 2025) - P1 | "This first-in-human, phase 1b study (NCT04294160) evaluated the safety, pharmacokinetics (PK), and preliminary antitumor activity of several rationally designed combinations in patients with BRAF V600-mutant CRC. This open-label, adaptive platform trial included a doublet backbone arm (BA: dabrafenib [DRB436; BRAF V600 inhibitor] + LTT462 [ERK1/2 inhibitor]) and 6 triplet arms (TAs): A1 (DRB436 + LTT462 + trametinib [TMT212; MEK1/2 inhibitor]), A2 (DRB436 + LTT462 + LXH254 [B/C-RAF inhibitor]), A3 (DRB436 + LTT462 + TNO155 [SHP2 inhibitor]), A4 (DRB436 + LTT462 + spartalizumab [anti–PD-1]), A5 (DRB436 + TMT212 + TNO155), and A6 (DRB436 + LTT462 + tislelizumab [anti–PD-1]). This multi-arm platform study demonstrated manageable safety across several MAPK pathway inhibitor combinations in BRAF V600-mutant CRC. Although RDs were not defined, preliminary efficacy and disease control results showed modest antitumor effect in all treatment arms."

Clinical • IO biomarker • Late-breaking abstract • Metastases • P1 data • Colorectal Cancer • Oncology • Solid Tumor • BRAF • DUSP6

CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov) - P1 | N=610 | Active, not recruiting | Sponsor: Amgen | Recruiting ➔ Active, not recruiting | N=1200 ➔ 610 | Trial primary completion date: Jun 2026 ➔ Dec 2026

Enrollment change • Enrollment closed • Monotherapy • Trial primary completion date • Brain Cancer • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Development of Patient-Derived Xenograft (PDX) Model with Acquired Resistance to KRASG12C Inhibitors (AACR-NCI-EORTC 2025) - "Then LU22002 was established from tumors of the same patient that progressed under combined treatment of MRTX849 and a SHP2 inhibitor, TNO155...Noticeably, all 6 mice treated with combined treatment of crizotinib and AMG510 showed complete tumor regression after 17 days of treatment. ConclusionWe have successfully developed KRASG12C inhibitor resistant NSCLC PDX models derived from one patient with acquired resistance to AMG510 and MRTX849 treatments, and in vivo induced KRASG12C inhibitor resistant PDX model. EGFR or MET gene amplification was observed in these resistant models, which can be used to evaluate innovative combination strategies."

Clinical • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • KRAS