Bry Sur Marne Cedex, France

Phase 1/2 Study Evaluating MCLA-129, a Human Anti-EGFR, Anti-c-MET Bispecific Antibody, in Advanced NSCLC and Other Solid Tumors, Alone and in Combination

Minnelide and Osimertinib for the Treatment of Advanced EGFR Mutated Non-Small Cell Lung Cancer

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) and the dose limiting toxicities (DLT) of triptolide analog (minnelide) capsules when given in combination with osimertinib. II. To establish the dose of minnelide capsules recommended for future phase II studies when given in combination with full dose osimertinib (recommended phase II dose [RP2D]). SECONDARY OBJECTIVES: I. To observe patients for any evidence of antitumor activity of minnelide capsules by objective radiographic assessment when in combination with osimertinib. II. To determine pharmacodynamic effects of minnelide capsules on heat shock protein (HSP)72 levels when given in combination with osimertinib. EXPLORATORY OBJECTIVES: I. Measure HSP levels, pre/post and during therapy as predictive biomarker. II. Determine levels of minnelide in the blood, and its effect. III. Determine the cell free deoxyribonucleic acid (DNA) in blood as biomarker. IV. Evaluate the microbiome pre-, during-, and post-therapy as potentiator of therapeutic response. V. Determine the exosomes as biomarker. OUTLINE: This is a dose-escalation study of minnelide. Patients receive minnelide orally (PO) once daily (QD) on days 1-21 and osimertinib PO QD on days 1-28. Cycles repeat every 28 days for 6 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 3 months for 2 years.

Additional Chemotherapy for EGFRm Patients with the Continued Presence of Plasma CtDNA EGFRm At Week 3 After Start of Osimertinib 1st-line Treatment (PACE-LUNG)

Hypothesize, that in patients with on-label osimertinib 1st-line treatment of stage IIIB or IV NSCLC, a biomarker-driven escalation of osimertinib therapy with a platinum-based chemotherapy regimen will effectively enhance PFS and subsequently OS. Lack of EGFRm clearance after an osimertinib treatment period of 3 weeks as assessed by liquid biopsy will be used to predict sub-optimal response. In these patients, treatment will be escalated after approx. 7 weeks of on-label osimertinib monotherapy by adding up to 4 cycles of a combination regimen of pemetrexed and cisplatin or carboplatin. Patients with complete EGFR plasma clearance will continue to receive standard of care osimertinib and will not be eligible for the study. Primary outcome measure will be PFS, which will be compared to historical data on TKI monotherapy from persistent EGFR shedder from the FLAURA trial.

Study to Evaluate VT3989 in Patients with Metastatic Solid Tumors

Dose escalation (Part 1) will employ a traditional 3 + 3 design to assess safety of VT3989 in patients with refractory metastatic solid tumors or mesothelioma. The 3 + 3 design will be implemented until the MTD or recommended phase 2 dose(s) and schedule(s) are determined. The MTD is defined as the highest dose level at which < 33% of patients experience a dose limiting toxicity (DLT) during the first cycle of the study (Cycle 1). Dose Expansion (Part 2) will further evaluate the safety and assess preliminary antitumor activity at the recommended phase 2 dose(s) and schedule(s) with up to 6 cohorts. Expansion cohorts 1 and 2 will enroll patients with mesothelioma of any site origin with or without NF2 mutations. Expansion cohort 3 will enroll non-pleural mesothelioma patients. Expansion cohort 4 will enroll solid tumor patients with clearly inactivating NF2 mutations/alterations or YAP/TAZ gene rearrangements. Cohort 5 will enroll pleural mesothelioma patients. Combination part (Part 3) includes two cohorts. Cohort A will enroll mesothelioma patients who will receive VT3989 in combination with immunotherapy (nivolumab plus ipilimumab). Cohort B will enroll NSCLC patients whose tumors have exon 19 deletion or exon 21 L858R mutation and will receive VT3989 in combination with targeted therapy (Osimertinib).

A Study to Evaluate the Safety, Tolerability, Drug Levels, and Preliminary Efficacy of BMS-986507 Combinations in Adult Participants With Advanced Solid Tumors

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

This is an open-label, multi-center, rollover study to assess long-term safety in participants who have completed a prior Novartis-sponsored study, that have fulfilled the eligibility requirements and are judged by the Investigator to benefit from continued treatment with capmatinib given as monotherapy or in combination with other treatments or with the combination treatment alone. There will be no screening period for this study. After providing informed consent, all eligible participants will begin their treatment within the rollover study. Participants should return to the study center for resupply of the study medication/s and for safety assessment following the usual local practice. During a public health emergency as declared by local or regional authorities (i.e. pandemic, epidemic or natural disaster) that limits or prevents on-site study visits, alternative methods of providing continuing care may be implemented by the Investigator as the situation dictates. Participants will continue to be treated until they are no longer benefitting from the study treatment in the opinion of the treating physician, develop unacceptable toxicities that preclude further treatment with the study treatment, disease progression, withdrawal of consent, discontinuation at the discretion of the Investigator, initiation of new anticancer therapy, until the study treatment is commercially available and reimbursed or/and available under any other local mechanism (such as compassionate use, named patient program) for the appropriate indication and/or discontinuation for any other reason. Participants receiving capmatinib as part of a combination therapy could continue treatment only with capmatinib or with the combination treatment as single agent in case one of the two compounds is permanently discontinued, if in the opinion of the treating physician they are still benefitting from the treatment. A patient will reach the end of rollover study when study treatment is permanently discontinued and the end of treatment visit has been performed. All participants will be followed up for safety for 30 days after the last dose of study treatment or until SAE is resolved as required, whichever is later. The study is expected to remain open for up to 10 years or until such time that all enrolled participants no longer need treatment with study treatment(s) or Novartis decides to stop the development program, whichever comes first.

Osimertinib Then Chemotherapy in EGFR-mutated Lung Cancer with Osimertinib Third-line Rechallenge

A Study of BL-B01D1 in Combination With Osimertinib Mesylate Tablets in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer

A Study of BL-B01D1 and BL-B01D1 in Combination With Osimertinib Mesylate Tablets in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer

A Phase 2 Study of Osimertinib and S-1 in Treatment Resistant EGFR Mutant NSCLC

A lead-in phase of 6 patients will be initiated prior to the formal phase II study. The planned sample size is 27 patients (lead-in and phase II). The primary objective of the study is to demonstrate that S-1 fixed dose 40 mg BD is safe and effective in EGFR metastatic lung cancer resistant to Osimertinib in terms of best overall response (BOR). The secondary objective of this study will be to further analyse the Disease Control Rate at stipulated timepoints (6,12 and 24 months), Progression-free survival, Overall Survival, and also the Toxicity by CTCAE 5.0.