Neoplasms

Symptoms and General Pathology

All Conditions

Skin and Connective Tissue Diseases

Neoplasm Metastasis

Breast Neoplasms

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Estrogens

Progesterone

Patients that express Estrogen receptor (ER), express Progesterone Receptor (PgR)+ (≥ 20%), don't express HER2 and have Ki-67 'low' (\< 14%).

Patients that express ER and are either PgR- or low (\< 20%) and/or Ki67 'high' (≥ 14%).

Patients that express ER and HER2 irrespective of PgR or Ki67 status.

Patients that express HER2 and don't express ER or PgR.

Patients who are negative for the expression of ER, PgR and HER2.

No intervention

MS Study Project Manager

Start-Up Unit Manager

Study Director

This study is a prospective, multicenter non-interventional cohort study designed to develop a registry in unresectable locally advanced or metastatic disease.

The target population for inclusion in this study is breast cancer patients recently diagnosed (from January 2016) with unresectable locally advanced or metastatic disease (either after a recurrence or as first diagnosis). No treatment regimen will be protocol specified. This is an observational study in which clinical decisions concerning the optimum management strategy for a particular patient are taken independently of and/or prior to, any decision by the physician to invite a patient to participate in the study. The treating physician will make all treatment decisions according to his/her regular clinical practice independent of this study. Patients enrolled on the study are free to withdraw their informed consent for the use and disclosure of health information at any time and when asked, patients are not obliged to provide a reason. Patients may request discontinuation from the study at any time.

The date and the reason for withdrawal or discontinuation from the study must be recorded in the electronic case report form (eCRF). An attempt will be made to determine the date of discontinuation and final status (i. e. withdrawal of consent, loss to follow-up, death) of any patient who discontinues from the study. However, the treating clinician is encouraged to follow the patient as long as possible, until patient death or through study end. The Sponsor has the right to terminate the study at any time. The Sponsor will notify the investigator if the study is placed on hold or if the Sponsor decides to discontinue the study.

Blood samples Primary and metastatic lesion tissue samples

A Prospective Registry Study in Patients With Unresectable Locally Advanced or Metastatic Breast Cancer (MBC)

Number of patients with the different breast cancer subtypes (Luminal A-like, Luminal B-like \[HER2 negative\], Luminal B-like \[HER2 positive\], HER2-enriched and Triple Negative) of the unresectable locally advanced or metastatic disease

It will be performed a table with patient and tumor characteristics including only those patients with heredofamiliar risk.

It will be performed an analysis separately for each subtype and by male and female and it will analyse if there are any significative difference between them.

Influence of timing of primary tumor surgery in patients with metastatic disease as first diagnosis

to improve the understanding of metastatic breast cancer by performing analysis on tumor and blood samples.

Hoffmann-La Roche

Novartis

AstraZeneca

Pfizer

Celgene

Spanish Breast Cancer Research Group

Digestive System Diseases

Rare Diseases

Stomach Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Stomach Cancer

Antineoplastic Agents

Capecitabine

Docetaxel

Oxaliplatin

DOX 4 cycles - Surgery - Follow-up

DOX:

Docetaxel 35 mg/m2 day 1 and 8 by one hour infusion; Oxaliplatin 80 mg/m2 day 1 by two hours infusion; Capecitabine 750 mg/m2 x 2 daily for 2 weeks, per OS.

Treatment should be administered for 4 cycles before surgery. Each cycle will be repeated every 3 weeks.

DOX 2 cycles - Surgery - DOX 2 cycles - Follow-up

DOX:

Docetaxel 35 mg/m2 day 1 and 8 by one hour infusion; Oxaliplatin 80 mg/m2 day 1 by two hours infusion; Capecitabine 750 mg/m2 x 2 daily for 2 weeks, per OS.

Treatment should be administered for 2 cycles before surgery and for further 2 cycles after surgery, unless progression of disease or unacceptable toxicity occurs, or patient refusal. In these cases patients will go off treatment.

Each cycle will be repeated every 3 weeks.

DOX 4 cycles - Surgery

DOX 2 cycles - Surgery - DOX 2 cycles

Manlio Monti, MD

Study design:

Multicenter, randomized, open label phase II study Arm A: DOX 4 cycles - Surgery - Follow-up Arm B: DOX 2 cycles - Surgery - DOX 2 cycles - Follow-up

Population:

Male or female, 18-75 years of age, with a diagnosis of histologically confirmed, potentially resectable adenocarcinoma of the stomach.

Sample Size: Planned sample size is 90 patients, 45 patients for each arm (p0=50%, p1=80%, alpha=0.05 (two sides), beta=0.2)

Treatment Plan:

Treatment will be administered for 4 and 2 cycles before surgery in arm A and B, respectively, and in arm B for a further 2 cycles after surgery unless progression or unacceptable toxicity occurs, or a patient refuses treatment. In such cases patients will go off treatment. 3-6 weeks after the end of the fourth (arm A) or second (arm B) preoperative cycle, patients will undergo surgery.

After surgery 3-6 weeks from surgery patients in arm B will receive 2 more cycles.

DOX: Docetaxel 35 mg/m2 day 1 and 8 Oxaliplatin 80 mg/m2 day 1 Capecitabine 750 mg/m2 x 2 daily for 2 weeks

Cycles repeated every 3 weeks

Evaluation criteria: Tumor assessment will be performed according to the RECIST criteria (version 1.1).

Duration of Study:

Overall study duration: 07/2010- 03/2017 Planned study duration per patient: 5 years

Title: A randomised phase II study of pre-operative or peri-operative docetaxel, oxaliplatin, capecitabine (DOX) regimen in patients with locally advanced resectable gastric cancer.

Clinical Phase: II

Study Objectives:

Primary:

The percentage of patients receiving all the planned chemotherapeutic cycles.

Secondary:

* Downstaging according to Recist criteria
* pT1-3 vs pT0.
* Safety: number of patients with grade 3-4 toxicity
* The role of PET Scan as predictor of response
* Curative vs palliative surgery
* TTP
* OS
* Diagnostic correlation between the various staging methods
* Possible correlations between CT scan, CT/PET, laparoscopy;
* Molecular markers related to toxicity: DPYD, MTHFR, TS, XPD, ERCC1, XRCC1;
* Molecular markers related to prognosis: TYMS, GSTP1, COX-2, RUNX3, methylation profile (Cox2, hMLH1, MGMT);
* Molecular markers related to therapy response: TYMS, DPYD, MTHFR, OPRT, ERCC1, XRCC1/2/3, GSTP1, GSTM1, GSTT1, ABCB1, methylation profile (Cox2, hMLH1, MGMT), whole genome arrayCGH.

Study design:

Multicenter, randomized, open label phase II study Arm A: DOX 4 cycles - Surgery - Follow-up Arm B: DOX 2 cycles - Surgery - DOX 2 cycles - Follow-up

Population:

Male or female, 18-75 years of age, with a diagnosis of histologically confirmed, potentially resectable adenocarcinoma of the stomach.

Sample Size: Planned sample size is 90 patients, 45 patients for each arm (p0=50%, p1=80%, alpha=0.05 (two sides), beta=0.2)

Treatment Plan:

Treatment will be administered for 4 and 2 cycles before surgery in arm A and B, respectively, and in arm B for a further 2 cycles after surgery unless progression or unacceptable toxicity occurs, or a patient refuses treatment. In such cases patients will go off treatment. 3-6 weeks after the end of the fourth (arm A) or second (arm B) preoperative cycle, patients will undergo surgery.

After surgery 3-6 weeks from surgery patients in arm B will receive 2 more cycles.

DOX: Docetaxel 35 mg/m2 day 1 and 8 Oxaliplatin 80 mg/m2 day 1 Capecitabine 750 mg/m2 x 2 daily for 2 weeks

Cycles repeated every 3 weeks

Evaluation criteria: Tumor assessment will be performed according to the RECIST criteria (version 1.1).

Duration of Study:

Overall study duration: 07/2010- 03/2017 Planned study duration per patient: 5 years

Pre-Operative Or Peri-Operative Dox Regimen In Patients With Locally Advanced Resectable Gastric Cancer

A Randomised Phase Ii Study Of Pre-Operative Or Peri-Operative Docetaxel, Oxaliplatin, Capecitabine (Dox) Regimen In Patients With Locally Advanced Resectable Gastric Cancer

To determine the percentage of tumors downstaged at the diagnosis, compared with the pathological stage detected at the time of surgery (according to Recist criteria)

Comparation of treatment tolerability and safety and tumor response between patients with pathological stage pT1-3 vs pT0 (detected at the time of surgery)

Evaluation of the role of PET as a tool to detect tumor response

Evaluation of possible correlations between the diagnostic techniques CT scan, CT/PET and laparoscopy

Biological detection of molecular markers related to treatment toxicity (DPYD, MTHFR, TS, XPD, ERCC1, XRCC1)

Biological detection of molecular markers related to treatment prognosis (TYMS, GSTP1, COX-2, RUNX3, methylation profile (Cox2, hMLH1, MGMT))

Biological detection of molecular markers related to therapy response (TYMS, DPYD, MTHFR, OPRT, ERCC1, XRCC1/2/3, GSTP1, GSTM1, GSTT1, ABCB1, methylation profile (Cox2, hMLH1, MGMT), whole genome arrayCGH)

Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

Antiemetics

Gastrointestinal Agents

Emetics

Dose escalation step Dose escalation will be conducted on the grid defined by the 4 doses of PLX038 (800 mg/m², 1000 mg/m², 1300 mg/m² and 1700 mg/m² IV every 21 days D1=D22) and 3 doses of Tuvusertib (90 mg, 130 mg and 180 mg QD for 10 days from D3, D3-12). Premedication with anti-emetic agents is not required prior to the initial infusion, but may be used for an individual patient, as needed.

Expansion cohorts Two expansion cohorts are planned, investigating the efficacy and safety in pre-specified populations of interest.

Patients will be treated at the RP2D; 25 evaluable patients are needed in each cohort, to account for possible non evaluable patients, up to 28 patients will be enrolled in each cohort.

Patients enrolled in the phase I part at the RP2D and fulfilling the eligibility criteria of one of the expansion cohorts will be counted in those 25 evaluable patients.

Dose escalation will be conducted on the grid defined by the 4 doses of PLX038 (800 mg/m², 1000 mg/m², 1300 mg/m² and 1700 mg/m² IV every 21 days D1=D22) and 3 doses of Tuvusertib (90 mg, 130 mg and 180 mg QD for 10 days from D3, D3-12). Premedication with anti-emetic agents is not required prior to the initial infusion, but may be used for an individual patient, as needed.

All included patients will receive PLX038 + Tuvusertib until progression of disease, unacceptable toxicity, patient withdrawal of consent, investigator decision, lost to follow-up, death, patient non-compliance, or study termination by Sponsor.

PLX038 + Tuvusertib

Fouzia Azzouz

François-Clément Bidard, Study Principal Investigator

François-Clément BIDARD

Phase I with a dose finding cohort, followed by expansion cohorts in pre-specified tumor types.

This is an open label, multi-centric phase I with, first, a dose escalation step using an adaptation of the Bayesian Optimal INterval (BOIN) drug-combination, followed by 2 dose expansion cohorts using the Simon 2-stage design.

Dose escalation step Dose escalation will be conducted on the grid defined by the 4 doses of PLX038 (800 mg/m², 1000 mg/m², 1300 mg/m² and 1700 mg/m² IV every 21 days D1=D22) and 3 doses of Tuvusertib (90 mg, 130 mg and 180 mg QD for 10 days from D3, D3-12). Premedication with anti-emetic agents is not required prior to the initial infusion, but may be used for an individual patient, as needed.

starting combination level is c1 (PLX038 800mg/m2 and Tuvusertib 90mg). Groups of 3 patients will be sequentially enrolled. One week between the enrollment of the 1st patient and the 2 following patients is mandatory at a new combination level. The decision to (de)-escalate one of the two agents depends on the outcome of all patients treated at the current combination.

Expansion cohorts Two expansion cohorts are planned, investigating the efficacy and safety in pre-specified populations of interest.

Patients will be treated at the RP2D; 25 evaluable patients are needed in each cohort, to account for possible non evaluable patients, up to 28 patients will be enrolled in each cohort.

Patients enrolled in the phase I part at the RP2D and fulfilling the eligibility criteria of one of the expansion cohorts will be counted in those 25 evaluable patients.

A Study on Tuvusertib (Oral ATR Inhibitor) in Combination With PLX038 (Topo1 Inhibitor) in Patients With Advanced Solid Tumors

A Phase I Study on Tuvusertib (Oral ATR Inhibitor) in Combination With PLX038 (Topo1 Inhibitor) With Dose Expansion Cohorts in Patients With Advanced Solid Tumors

Sponsor will share de-identified data sets. Documents generated under the project will be disseminated in accordance with Institut Curie policies.

Dose limiting toxicities (DLTs) experienced during 21 days from the first IV infusion of PLX038 + Tuvusertib

Best tumor response (defined as PR or CR in the first 6 months of treatment, assessed by investigators per RECIST v1.1 criteria)

Serious Adverse Events (SAEs) according to NCI CTCAE v5.0 by grade and their relationship to PLX038 + Tuvusertib.

Adverse Events (AEs) according to NCI CTCAE v5.0 by grade and their relationship to PLX038 + Tuvusertib.

Maximum Plasma Concentration effect of PLX038, SN38 and Tuvusertib

ORR defined as the percentage of patients with complete response (CR) or partial response (PR), as the best response measured at the disease assessmement after initiation of treament according to RECIST v1.1

TTR calculated from the initiation of treatment to best tumour response (CR/PR)

DoR defined as the time period from best tumour response to disease progression (according to RECIST v1.1)

PFS measured from the inclusion in the study to the first documented progression (according to RECIST v1.1) or death from any cause.

DoR defined as the time period from best tumour response to disease progression

PFS measured from the inclusion in the study to the first documented progression

OS is defined as the time from inclusion to the event death.

Association between PLX038 + Tuvusertib efficacy and homologous recombination (HR) defect (assessed by HR genes mutational status and BCRAness phenotype), replication stress-related biomarkers such as SFLN11 expression, RB1 loss; genomic alterations in DDR genes

Association between PLX038 + Tuvusertib efficacy and quantitative changes of blood biomarkers (e.g. ctDNA) during therapy.

ProLynx LLC

Merck Sharp & Dohme LLC

Institut Curie

Triple Negative Breast Neoplasms

Patients will be treated at a dose of 1730mg/m2 IV infusion on Day 1 of each cycle Q3W (every 21 days, 1 cycle = 1 injection) after at least a first cycle at 1300mg/m2. At the discretion of the treating physician, the PLX038 dose will be increased to 1730 mg/m2 for patients who tolerate at least 1 cycle without any of the following toxicities: febrile neutropenia, grade 4 neutropenia for \> 5 days or ANC \< 100 109/L for more than 1 day, or other non-hematological toxicities of Grade \> 2 \[NCI-CTCAE, Version 5\].

Study treatment will be at a dose of 1730mg/m2 IV infusion on Day 1 of each cycle Q3W (every 21 days, 1 cycle = 1 injection) after at least a first cycle at 1300mg/m2.

Patients with a clinical benefit could be treated as long as study is ongoing. Patients are followed from inclusion until documented disease progression, withdrawal of consent, or death.

PLX038

François-Clément Bidard

Single arm phase II study for with primary objective to evaluate the efficacy of PLX038 on response rate for patients with pretreated, metastatic or locally advanced triple negative breast cancer.

This is an open label, multi-centric phase II study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of PLX038 in locally-advanced or metastatic TNBC. Patient must have received prior therapy (administered in the neoadjuvant, adjuvant and/or metastatic setting) with an anthracycline, taxane and sacituzumab-govitecan (unless not medically appropriate or contraindicated for the patient) and Received a minimum of two prior cytotoxic chemotherapy regimens for locally advanced or metastatic breast cancer.

Patients will be treated at a dose of 1730mg/m2 IV infusion on Day 1 of each cycle Q3W (every 21 days, 1 cycle = 1 injection) after at least a first cycle at 1300mg/m2. At the discretion of the treating physician, the PLX038 dose will be increased to 1730 mg/m2 for patients who tolerate at least 1 cycle without any of the following toxicities: febrile neutropenia, grade 4 neutropenia for \> 5 days or ANC \< 100 109/L for more than 1 day, or other non-hematological toxicities of Grade \> 2 \[NCI-CTCAE, Version 5\].

All included patients will receive PLX038 as single agent as long as study is ongoing or until progression of disease, unacceptable toxicity, patient withdrawal of consent, Investigator decision, lost to follow-up, death, patient non-compliance, or study termination by Sponsor.

Tumor assessments must be performed according to the RECIST V1.1 criteria at inclusion and every 8 weeks (± 7 days) from inclusion until documented disease progression, withdrawal of consent, or death. Radiographic measurements must be performed to the RECIST specifications.

A Study to Evaluate the Efficacy and Toxicities of PLX038, in Patients With Locally Advanced or Metastatic Triple-negative Breast Cancer

A Phase II Study to Evaluate the Efficacy and Toxicities of PLX038, in Patients With Locally Advanced or Metastatic Triple-negative Breast Cancer

Best tumor response (defined as PR or CR in the first 6 months of treatment, assessed by investigators per RECIST v1.1 criteria).

Time to response is defined as the time from inclusion to the first objective tumor response and will be estimated using Kaplan-Meier method

Serious adverse events (SAEs)according to NCI CTCAE v5.0, by grade and their relationship to PLX038

Incidence of efficacy of PLX038 in pre-defined biomarker subgroups (BRCAness)

Maximum Plasma Concentration effect of PLX038

DoR is defined as the time from the first documented PR or CR until the date of disease progression or the date of death. DoR will be computed using Kaplan-Meier

PFS is defined as the time from inclusion to progression (per RECIST 1.1) or death, among included patients

PFS is defined as the time from inclusion to the first event among progression and death. OS is defined in the same way but only death is taken into account.

Adverse events (AEs) according to NCI CTCAE v5.0, by grade and their relationship to PLX038

Incidence of efficacy of PLX038 in pre-defined biomarker subgroups (SLFN11 expression)

Incidence of efficacy of PLX038 in pre-defined biomarker subgroups (RB1 loss)

Maximum Plasma Concentration of effect of PLX038

Gland and Hormone Related Diseases

Pancreatic Neoplasms

Endocrine Gland Neoplasms

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Participants will receive FG-3019 35 milligrams (mg)/kilogram (kg) by intravenous (IV) infusion on Days 1 and 15 of each treatment cycle and on Day 8 of the first cycle, gemcitabine 1000 mg/square meter (m\^2) and nab-paclitaxel 125 mg/m\^2 by IV infusion on Days 1, 8, and 15 of each treatment cycle. Treatment will be administered over a 28-day cycle, for up to 6 cycles.

Participants will receive gemcitabine 1000 mg/ meter squared (m\^2) and nab-paclitaxel 125 mg/m\^2 by IV infusion on Days 1, 8, and 15 of each treatment cycle. Treatment will be administered over a 28-day cycle, for up to 6 cycles.

FG-3019 will be administered per dose and schedule specified in the arm group description.

FG-3019

Gemcitabine will be administered per dose and schedule specified in the arm group description.

Nab-paclitaxel will be administered per dose and schedule specified in the arm group description.

Nab-paclitaxel

Vincent Picozzi, MD

This is a Phase 1/2 trial to evaluate the safety, tolerability, and efficacy of FG-3019 administered with gemcitabine and nab-paclitaxel in the treatment of locally advanced, unresectable pancreatic cancer.

A Study of Gemcitabine Plus Nab-paclitaxel With or Without FG-3019 in Participants With Locally Advanced, Unresectable Pancreatic Cancer

A Randomized, Open Label, Phase 1/2 Trial of Gemcitabine Plus Nab-paclitaxel With or Without FG-3019 as Neoadjuvant Chemotherapy in Locally Advanced, Unresectable Pancreatic Cancer

An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. SAEs included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A TEAE was defined as a new or worsening AE that occurred in the window of first infusion of any study drug (Day 1) and within 28 days of the last infusion of study drug or the day before surgery, whichever occurred first. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'.

Number of participants who had surgical complications (for example; surgical site infection, intra-abdominal abscess, or perioperative leak during surgery) has been reported

R0 resection was determined by pathological examination of the surgical specimen after resection.

R0 or R1 resection was determined by pathological examination of the surgical specimen after resection.

CR was defined as disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduced in short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Overall survival was defined as the time from randomization until death from any cause.

Progression-free survival was defined as the time from randomization until objective tumor progression or death. Progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression.

FibroGen

Safety population included all participants who had received any dose of study drug.

Participants received gemcitabine at 1000 mg/m\^2 plus nab-paclitaxel at 125 mg/m\^2 by IV infusion on Days 1, 8, and 15 of each cycle. Participants received pamrevlumab at 35 mg/kg by IV infusion on Days 1 and 15 of each cycle. An additional dose of pamrevlumab was given on Day 8 of the first cycle. Participants received a total of up to six 28-day cycles of treatment.

Arm A: Gemcitabine Plus Nab-paclitaxel + Pamrevlumab (G/NP+P)

Participants received gemcitabine at 1000 mg/ m\^2 plus nab-paclitaxel at 125 mg/m\^2 by IV infusion on Days 1, 8, and 15 of each cycle. Participants received a total of up to six 28-day cycles of treatment.

Arm B: Gemcitabine Plus Nab-paclitaxel (G/NP)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Intent-to-treat (ITT) population included all randomized participants who received any amount of study drugs including pamrevlumab, or gemcitabine, or nab-paclitaxel.

Clinical Trial Information Desk

TEAEs

SAEs

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

ITT population included all randomized participants who received any amount of study drugs including pamrevlumab, or gemcitabine, or nab-paclitaxel.

Number of Participants Who Had Surgical Complications Post-Resection

Number of Participants Who Became Eligible for Surgery

Number of Participants in Whom R0 Resection Was Achieved

Number of Participants in Whom R0 or R1 Resection Was Achieved

Number of Participants With Complete Response (CR) or Partial Response (PR) Per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

Median Overall Survival

Median Progression-Free Survival

Participants received gemcitabine at 1000 milligrams (mg)/ meters (m)\^2 plus nab-paclitaxel at 125 mg/m\^2 by intraveneous (IV) infusion on Days 1, 8, and 15 of each cycle. Participants received pamrevlumab at 35 mg/kilograms (kg) by IV infusion on Days 1 and 15 of each cycle. An additional dose of pamrevlumab was given on Day 8 of the first cycle. Participants received a total of up to six 28-day cycles of treatment.

Overall Study

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Amino Acids

Osimertinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Savolitinib 300 mg oral QD

Osimertinib 80 mg oral QD

Savolitinib 300 mg oral QD

Placebo to Osimertinib 80mg oral QD

Osimertinib 80 mg oral QD

Savolitinib 300mg oral QD

Osimertinib + Savolitinib

Savolitinib 300mg Oral QD

Placebo to Osimertinib 80mg oral QD

Savolitinib + Placebo

This study will compare the activity of the combination of savolitinib and osimertinib against the combination of savolitinib with placebo to osimertinib in patients with Epidermal Growth Factor Receptor Mutation Positive and MET amplified, locally advanced or metastatic non-small cell lung cancer who have progressed following treatment with osimertinib.

Resistance to EGFR-TKIs is a clinical problem. One of the mechanisms for resistance to osimertinib is amplification of the MET receptor tyrosine kinase, which activates downstream intracellular signalling independent of EGFR. This study will explore the individual contribution of savolitinib to MET mediated osimertinib resistance, by assessing the response to dual pathway blockade of EGFRm and MET to overcome MET mediated resistance to osimertinib versus inhibition of the MET pathway alone by investigating the efficacy of savolitinib plus osimertinib versus savolitinib plus placebo to osimertinib (hereafter referred to as placebo) in patients with EGFRm+ and MET amplified, locally advanced or metastatic NSCLC who have progressed following treatment with osimertinib. This is a multi centre, Phase II, double blind, randomised study.

Patients will be randomised in a ratio of 1:1 to receive treatment with savolitinib once daily plus osimertinib once daily or savolitinib once daily plus placebo. Randomisation will be stratified according to the number ofprior lines of therapy (ie, osimertinib monotherapy as first line or ≥ second line \[which includes patients who received osimertinib monotherapy before or after chemotherapy\]). All patients confirmed as eligible will begin treatment on Day 1 with savolitinib plus osimertinib or savolitinib plus placebo. Treatment will continue once daily in 28 day cycles until either objective PD by RECIST 1.1 is assessed, unacceptable toxicity occurs, consent is withdrawn, or another discontinuation criterion is met.

After progression, patients can be unblinded, and patients initially randomised to the savolitinib plus placebo arm may cross-over to open-label savolitinib plus osimertinib following investigator assessed objective PD to ensure that all patients enrolled may have the opportunity to receive the combination of savolitinib plus osimertinib.

1. Patients will take savolitinib 300mg tablets QD within 15 minutes after the start of a meal except for the day on which PK samples are taken. Patients will take osimertinib 80mg tablet once daily with/without food except for the day on which PK samples are taken. On the day when PK samples are taken both savolitinib \& osimertinib will be administered after a meal prepared by the clinic
2. Patients will take savolitinib 300mg tablets QD within 15 minutes after the start of a meal except for the day on which PK samples are taken. Patients will take placebo to osimertinib 80mg tablet once daily with/without food except for the day on which PK samples are taken. On the day when PK samples are taken both savolitinib \& placebo to osimertinib will be administered within 15 minutes after a meal prepared by the clinic

In addition to comparing the ORR between groups, this study will also assess safety and tolerability, DoR, DCR, OS, PFS and other measures of antitumor activity

A Study Comparing Savolitinib Plus Osimertinib vs Savolitinib Plus Placebo in Patients With EGFRm+ and MET Amplified Advanced NSCLC

A Multi-centre Phase II, Double-Blind, Randomised Study of Savolitinib in Combination With Osimertinib vs Savolitinib in Combination With Placebo in Patients With EGFRm+ and MET Amplified Locally Advanced or Metastatic Non-Small Cell Lung Cancer Who Have Progressed Following Treatment With Osimertinib

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

To collect and store germline DNA for exploration of the role of HLA alleles in developmental toxicity.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Prospective Registry Study in Patients With Unresectable Locally Advanced or Metastatic Breast Cancer (MBC)	NCT02819882	Breast Neoplasm...	No intervention	18 Years -	Spanish Breast Cancer Research Group
Pre-Operative Or Peri-Operative Dox Regimen In Patients With Locally Advanced Resectable Gastric Cancer	NCT01876927	Gastric Cancer Locally Advance...	DOX 4 cycles - ... DOX 2 cycles - ...	18 Years - 75 Years	Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
A Study on Tuvusertib (Oral ATR Inhibitor) in Combination With PLX038 (Topo1 Inhibitor) in Patients With Advanced Solid Tumors	NCT06337630	Solid Tumor	PLX038 + Tuvuse...	18 Years -	Institut Curie
A Study to Evaluate the Efficacy and Toxicities of PLX038, in Patients With Locally Advanced or Metastatic Triple-negative Breast Cancer	NCT06162351	Breast Cancer	PLX038	18 Years -	Institut Curie
A Study of Gemcitabine Plus Nab-paclitaxel With or Without FG-3019 in Participants With Locally Advanced, Unresectable Pancreatic Cancer	NCT02210559	Pancreatic Canc...	FG-3019 Gemcitabine Nab-paclitaxel	18 Years -	FibroGen
A Study Comparing Savolitinib Plus Osimertinib vs Savolitinib Plus Placebo in Patients With EGFRm+ and MET Amplified Advanced NSCLC	NCT04606771	Non-Small Cell ...	Osimertinib + S... Savolitinib + P...	18 Years -	AstraZeneca
A Study of LY2523355 in Participants With Breast Cancer	NCT01416389	Metastatic Brea...	LY2523355 ixabepilone pegfilgrastim filgrastim	18 Years -	Eli Lilly and Company
A Study of LY2523355 in Participants With Breast Cancer	NCT01416389	Metastatic Brea...	LY2523355 ixabepilone pegfilgrastim filgrastim	18 Years -	Eli Lilly and Company

Spots Global Cancer Trial Database for locally

Every month we try and update this database with for locally cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for locally

Every month we try and update this database with for locally cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for locally cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.