nazartinib (EGF816) / Novartis - LARVOL DELTA

Study of EGF816 in Combination With Selected Targeted Agents in EGFR-mutant NSCLC (clinicaltrials.gov) - P1 | N=105 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Oct 2025 ➔ Mar 2026 | Trial primary completion date: Oct 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • 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=227 | Terminated | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Terminated; Business reasons and not due to any safety concerns

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

Study to Allow Patients Previously Participating in a Novartis Sponsored Trial to Continue Receiving Capmatinib Treatment as Single Agent or in Combination With Other Treatments or the Combination Treatment Alone (clinicaltrials.gov) - P2 | N=29 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Monotherapy • Solid Tumor

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

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

A Study of EGF816 and Gefitinib in TKI-naïve EGFR-mutant Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=11 | Terminated | Sponsor: Massachusetts General Hospital | Active, not recruiting ➔ Terminated; Slow accrual

Trial termination • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

EATON: A phase I trial of nazartinib (EGF816) and trametinib in EGFR-mutant (EGFRmut) non-small cell lung cancer (NSCLC). (ASCO 2025) - P1 | "At the MTD, treatment was safe and moderately tolerable. Preliminary efficacy in this unselected and heavily pre-treated population was limited. A comprehensive biomarker-driven approach may help identify patients more likely to derive clinical benefit."

P1 data • Cardiovascular • Hypertension • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET

A first-in-human study of oral TNO155 (batoprotafib) alone and in combination with EGF816 (nazartinib) in adult patients with advanced solid tumors (AACR 2025) - P1 | "Arm B EXP required progression on osimertinib as the most recent prior therapy. As of 1-Aug-2024, 227 pts were treated (Arm A: ESC; n=141; EXP; n=42; Arm B; ESC; n=29; EXP; n=15), and 224 (98.6%) pts had discontinued study treatment, mainly due to progressive disease. TNO155 shows acceptable safety as a SA and with nazartinib and demonstrates evidence of MAPK pathway suppression in tumors."

Clinical • Combination therapy • Metastases • P1 data • Cutaneous Melanoma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • DUSP6 • KRAS • NRAS

Study of EGF816 in Combination With Selected Targeted Agents in EGFR-mutant NSCLC (clinicaltrials.gov) - P1 | N=105 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Apr 2025 ➔ Oct 2025 | Trial primary completion date: Apr 2025 ➔ Oct 2025

Trial completion date • Trial primary completion date • 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=227 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: May 2025 ➔ Nov 2025 | Trial primary completion date: May 2025 ➔ Nov 2025

Trial completion date • Trial primary completion date • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • KRAS

Study of EGF816 in Combination With Selected Targeted Agents in EGFR-mutant NSCLC (clinicaltrials.gov) - P1 | N=105 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Dec 2024 ➔ Apr 2025 | Trial primary completion date: Dec 2024 ➔ Apr 2025

Combination therapy • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Characterization of the in vitro metabolic profile of nazartinib in HLMs using UPLC-MS/MS method: In silico metabolic lability and DEREK structural alerts screening using StarDrop software. (PubMed, Heliyon) - "In the context of computational software, making minor adjustments or substituting the dimethylamino-butenoyl moiety throughout the drug design process may increase the metabolic stability and safety properties of new synthesized derivatives. The efficiency of utilizing different in silico software approaches to conserve resources and reduce effort was proved by the outcomes attained from in vitro incubation experiments and the use of NZT in silico software."

Journal • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

A Study of EGF816 and Gefitinib in TKI-naïve EGFR-mutant Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=11 | Active, not recruiting | Sponsor: Massachusetts General Hospital | Trial completion date: Jun 2024 ➔ Dec 2024

Trial completion date • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Capmatinib plus nazartinib in patients with EGFR-mutated non-small cell lung cancer. (PubMed, Eur J Cancer) - P1/2 | "Capmatinib plus nazartinib showed antitumor activity in patients with EGFR-TKI-resistant, EGFR-mutated NSCLC. The overall safety profile was acceptable."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Capmatinib Plus Nazartinib in Patients With EGFR-Mutated Non–Small Cell Lung Cancer (Eur J Cancer) - P1b/2 | N=177 | NCT02335944 | Sponsor: Novartis Pharmaceuticals | "The RP2D was capmatinib 400 mg bid plus nazartinib 100 mg qd. In phase 2 (n=144), the ORR was 28.8%, 33.3%, 61.7%, and 42.9% in groups 1 (n=52), 2 (n=3), 3 (n=47), and 4 (n=42), respectively. In group 1+phase 1b RP2D, the ORR was 45.8%, 26.2%, 37.9%, and 32.4% in MET+ (n=24), MET− (n=42), T790M+ (n=29), and T790M− (n=34) patients. Most common any-grade treatment-related adverse events (≥25%; n=144) were peripheral edema (54.9%), nausea (41.7%), diarrhea (34.0%), and maculopapular rash (25.0%)."

P1/2 data • Non Small Cell Lung Cancer

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 • Metastases • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • KRAS

EATON: EGF816 and Trametinib in Patients With Non-small Cell Lung Cancer Harboring Activating EGFR Mutations (clinicaltrials.gov) - P1 | N=18 | Completed | Sponsor: University of Cologne | Recruiting ➔ Completed | Trial completion date: Apr 2023 ➔ Nov 2023

Trial completion • Trial completion date • 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: Oct 2024 ➔ Apr 2025 | Trial primary completion date: Oct 2024 ➔ Apr 2025

Metastases • Trial completion date • Trial primary completion date • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • KRAS

ESMO 2023: Updates in Non-Small Cell Lung Cancer (NSCLC) : Episode 6: Innovations Needed and Future Directions in Treatment of NSCLC (AJMC) - "Concluding thoughts on data presented at ESMO 2023, and innovations still needed for improved survival of NSCLC-provided by Patrick Forde, MBBCh."

Video

A Phase I/II, Multicenter, Open-label Study of EGFRmut-TKI EGF816, Administered Orally in Adult Patients With EGFRmut Solid Malignancies (clinicaltrials.gov) - P1/2 | N=225 | Completed | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Study of EGF816 in Combination With Selected Targeted Agents in EGFR-mutant NSCLC (clinicaltrials.gov) - P1 | N=105 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Mar 2024 ➔ Sep 2024 | Trial primary completion date: Mar 2024 ➔ Sep 2024

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

SHP2 Inhibitors Undergo Exploration in Combinations (Targeted Oncology) - "Melissa Johnson, MD, discussed SHP2 inhibitors with Targeted Therapies in Oncology....Overall, the safety profiles of the SHP2 inhibitors undergoing development are comparable, according to Johnson. 'In my opinion, [the SHP2 inhibitors] have very similar mechanisms of action, with similar [adverse] effect profiles that include peripheral and pulmonary edema, decreases in ejection fraction, and some cytopenias,' Johnson said."

Media quote

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

Metastases • Trial completion date • Trial primary completion date • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • KRAS

A Study of EGF816 and Gefitinib in TKI-naïve EGFR-mutant Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=11 | Active, not recruiting | Sponsor: Massachusetts General Hospital | Trial completion date: Oct 2025 ➔ Jun 2024 | Trial primary completion date: Oct 2022 ➔ Dec 2023

Trial completion date • Trial primary completion date • Gastrointestinal Cancer • 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: Aug 2023 ➔ Feb 2024 | Trial primary completion date: Aug 2023 ➔ Feb 2024

Trial completion date • Trial primary completion date • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • KRAS

A Phase I/II, Multicenter, Open-label Study of EGFRmut-TKI EGF816, Administered Orally in Adult Patients With EGFRmut Solid Malignancies (clinicaltrials.gov) - P1/2 | N=225 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Oct 2023 ➔ Jun 2023

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