Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Amino Acids

Vitamins

Pembrolizumab

Carboplatin

Lenvatinib

Pemetrexed

Tyrosine Kinase Inhibitors

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Protein Kinase Inhibitors

Tyrosine

Folinic Acid

Folate

Vitamin B9

Dr Joanne Chiu, MBBS

Dr James Ho, MBBS

Adding chemotherapy or anti-VEGF to immunotherapy is an emerging strategy to enhance the efficacy of immunotherapy in many cancers. This phase 2 study aims to explore the preliminary efficacy of combination pembrolizumab with lenvatinib and chemotherapy in NSCLC patients with sensitizing EGFR, ALK, or ROS1 genetic aberration refractory to standard targeted therapy.

Pembrolizumab, Lenvatinib and Chemotherapy After TKIs in NSCLC

A Phase 2 Open-label Single-arm Study to Evaluate the Combination of Pembrolizumab, Lenvatinib and Chemotherapy in Non-small Cell Lung Cancer (NSCLC) Harbouring Targetable Mutation and Failed Standard Tyrosine Kinase Inhibitors

Proportion of patients who have a confirmed CR or PR per RECIST 1.1

Time from randomization to the first documented disease progression per RECIST 1.1 or death due to any cause, whichever occurs first

Time from randomization to death from any cause or last follow-up date

Dr Joanne CHIU

Assistant Professor

Crizotinib

Patients with stage IV or incurable non-squamous non-small cell lung cancer with a documented ROS1 rearrangement will be assigned to this arm.

Patients with stage IV or incurable non-squamous non-small cell lung cancer with a documented MET-activating mutation (exon 14) will be assigned to this arm.

Patients with stage IV or incurable non-squamous non-small cell lung cancer with a documented MET-amplification will be assigned to this arm.

Crizotinib is an orally administered, chemotherapy drug that works by blocking ALK, MET and ROS1 receptor tyrosine kinases from working.

Participants will receive crizotinib, orally (by mouth), at a dose of 250 mg, twice per day, every day of each 28 day cycle.

Natasha Leighl, M.D.

Natasha Leighl

Natasha Leighil, M.D.

This is a phase 2 study of a drug called crizotinib in people with metastatic (the cancer has spread to other parts of the body) non-small cell lung cancer with a mutation (change) in genes called ROS1 or MET. The purpose of this study is to look at how effective crizotinib is at treating ROS1 or MET mutated non-small cell lung cancer.

Crizotinib, also called XALKORI, is a chemotherapy drug that is currently approved for the treatment of ALK- or ROS1- positive advanced non-small cell lung cancer.

The study consists of a screening period, study drug period, end of study drug visit and follow-up period.

During the screening period, participants will be asked to have tests and procedures done to make sure that they are eligible to continue in the study. Screening may take several visits. Participants found to be eligible to continue in the study, will then enter the study drug period where they will take the study drug and have tests and procedures done about once a week for safety and for research purposes.

Participants who stop the study drug completely for any reason, will be asked to return to the clinic for an end of study drug visit about 28 days after their last dose of study drug to have tests and procedures done for safety and for research purposes. Participants that are experiencing any side effects during this time, will be closely followed by their study Doctor until the side effects have resolved or stabilized.

Participants who discontinue study drug for any reason other than disease progression, will be asked to have radiological imaging every 8 weeks to follow up on the status of their disease, until disease progression or the start a new treatment for their cancer.

After their final visit, the study nurse will call participants approximately every 3 months to check on the status of their health.

Participants will be assigned to one of the following:

Cohort 1 - ROS1 rearrangement Cohort 2 - MET-activating mutation (exon 14) Cohort 3 - MET-amplification

Study of Crizotinib for ROS1 and MET Activated Lung Cancer

Phase II Study of Crizotinib for ROS1 and MET Activated Lung Cancer (CROME)

Time from randomization to treatment discontinuation for any reason

Patient related symptom improvement evaluated by ESAS

Patient preference/health related utility evaluated by EQ5D-5L Questionnaire

Number of days from the date of randomization to the date of death

Pfizer

University Health Network, Toronto

Symptoms and General Pathology

Nervous System Diseases

Neoplasm Metastasis

Brain Neoplasms

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Repotrectinib 160 mg orally (PO) every day (QD) for 14 days, and 160 mg twice a day (BID) thereafter.

Repotrectinib is administered orally in capsule form, with each capsule containing size 0 hard gelatin 40 mg of the active compound in bottles containing 30 capsules.

Repotrectinib is administered orally in the form of capsules. The capsules are taken by mouth and swallowed intact (without chewing, crushing, or opening) with water or another suitable liquid.

Repotrectinib

Griselda Martrat

Susana Vitorino

Matthias Preusser, md

Barbara Kiesewetter, MD

Thorsten Füreder, MD

REPOSE is a phase II clinical trial exploring the safety and efficacy of repotrectinib in patients with non-small cell lung cancer (NSCLC) characterized by the presence of brain metastasis (BM) and whose tumors have mutated ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) gene.

REPOSE is an international multicenter, open-label, single arm phase II clinical trial designed to evaluate the efficacy of repotrectinib in patients with ROS1-positive NSCLC with BM.

Upon meeting all selection criteria, a total of 20 participants confirmed ROS1 rearrangement will be enrolled. Participants who have received prior chemotherapy, immunotherapy or other non-ROS1 tyrosine kinase inhibitor (TKI) are eligible.

Patients will continue study treatment until end of treatment (EoT) defined as the date of disease progression, death, or discontinuation from the study treatment for any other reason. After study treatment discontinuation, all participants will undergo a safety visit (at 28 ± 7 days after last treatment dose) in order to follow up toxicities and changes in concomitant medication. Patients discontinuing the study treatment at any time will enter a post-treatment follow-up period during which survival and subsequent anticancer therapy information will be collected every 3 months (± 7 days) from the safety visit until death, lost to follow-up, elective withdrawal from the study, or the end of study (EoS), whichever occurs first. Patients who discontinue treatment without evidence of disease progression will be also followed for tumor assessments until documented progression, elective withdrawal from the study, the start of new anti-cancer treatment, or the EoS.

EoS is estimated to occur approximately 13 months after the last patient included in the study initiates repotrectinib treatment, unless consent withdrawal, patient is lost to follow-up, death, or premature termination of the study. EoS is defined as the last data collection point at the last participant's safety visit and will occur after the study treatment termination of the last patient in the study.

The main objective of REPOSE study is to determine the efficacy of repotrectinib at any timepoint during the study period as determined locally by best central nervous system (CNS) response, that is in terms of intracranial objective response rate (IC-ORR).

REPotrectinib in ROS1-positive Non-small Cell Lung Cancer Patients With Active Brain mEtastasis

A Phase II Study Assessing Safety and Efficacy of REPotrectinib in ROS1-positive Non-small Cell Lung Cancer Patients With Active Brain mEtastasis (REPOSE Study)

Gene expression profiling analyses performed on blood samples to investigate the potential association with clinical outcomes.

ROS1 gene expression analysis performed on baseline tumor tissue samples to investigate the potential association with clinical outcomes.

Analysis of oncological biomarkers, such as growth rate of tumor derived by tumor growth rate modeling or tumor heterogeneity according to quantitative estimation through radiomics, may be performed on radiological images to investigate the potential association with clinical outcomes.

To assess the efficacy in terms of IC-ORR at any timepoint defined as the rate of patients with partial response (PR) or complete response (CR) for IC lesions, as determined locally by the investigator as judged by best CNS response according to the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria.

To assess the efficacy in terms of CBR, defined as the rate of patients with objective response (CR or PR), or stable disease (SD) for IC lesions for at least 24 weeks, as determined locally by the investigator using RANO-BM.

To assess the efficacy in terms of DCR, defined as the percentage of patients with advanced cancer whose therapeutic intervention has led to a CR, PR, or SD for IC lesions, as determined locally by the investigator using RANO-BM.

To assess the efficacy in terms of TTR, defined as the period from the treatment initiation to time of the first objective tumor response (tumor shrinkage of ≥ 30%) observed for patients who achieved a CR or PR for IC lesions, as determined locally by the investigator using RANO-BM.

To assess the efficacy in terms of DoR, defined as the period from the first occurrence of a documented objective response to disease progression or death from any cause, observed for patients who achieved a CR or PR for IC lesions, as determined locally by the investigator using RANO-BM.

To assess the efficacy in terms of EC-ORR at any timepoint defined as the rate of patients with partial response (PR) or complete response (CR) for EC and overall lesions, as determined locally by the investigator using Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v.1.1) criteria.

To assess the efficacy in terms of CBR at any timepoint defined as the rate of patients with objective response (CR or PR), or SD for EC and overall lesions, for at least 24 weeks, as determined locally by the investigator using RECIST v.1.1

To assess the efficacy in terms of DCR, defined as the percentage of patients with advanced cancer whose therapeutic intervention has led to a CR, PR, or SD for EC and overall lesions, as determined locally by the investigator using RECIST v.1.1

To assess the efficacy in terms of TTR, defined as the period from the treatment initiation to time of the first objective tumor response (tumor shrinkage of ≥ 30%) observed for patients who achieved a CR or PR for EC and overall lesions, as determined locally by the investigator using RECIST v.1.1

To assess the efficacy in terms of DoR, defined as the period from the first occurrence of a documented objective response to disease progression or death from any cause, observed for patients who achieved a CR or PR for EC and overall lesions, as determined locally by the investigator using RECIST v.1.1.

To evaluate the best percentage of change in tumor burden determined locally by the investigator using RANO-BM criteria for IC lesions and RECIST v.1.1 for EC and overall lesions.

To assess the PFS, defined as the period from treatment initiation to the first occurrence of disease progression or death from any cause, whichever occurs first, determined locally per RANO-BM criteria for IC lesions and RECIST criteria v.1.1 for EC and overall lesions.

To determine the OS, defined as the period from treatment initiation to death from any cause, determined locally by the investigator.

To assess the patient neurologic function with the Neurologic Assessment in Neuro-Oncology (NANO) scale

To evaluate changes from baseline and during repotrectinib treatment in terms of patient-reported outcome (PRO) assessments of QoL and treatment-related symptoms as measured by EORTC QLQ-C30 scale.

EORTC QLQ-C30 scale aims to measure cancer patients' physical, psychological and social functions. Scale and single items are transformed into scores ranging from 0 to 100. A high score for a functional scale represents a high level of functioning, whereas a high score for a symptom scale/single item represents a high level of symptomatology.

To evaluate changes during repotrectinib treatment in terms of PRO assessments of QoL and treatment-related symptoms as measured by EORTC QLQ-C20 scale.

EORTC QLQ-BN20 brain specific tool aims to measure the effects of brain tumors and its treatment on symptoms, functions and health-related quality of life.

Scale and single items are transformed into scores ranging from 0 to 100. A high score for a functional scale represents a high level of functioning, whereas a high score for a symptom scale/single item represents a high level of symptomatology.

To evaluate the safety and toxicity profile of treatment with of repotrectinib as per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.

Medical University of Vienna

MedSIR

Disease Progression

Disease Attributes

Patients receive brigatinib PO QD and binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Binimetinib

Brigatinib

Collin Blakely, MD, PhD

This phase I trial studies the side effects and best dose of brigatinib and binimetinib in treating patients with stage IIIB-IV non-small cell lung cancer and a type of gene mutation called a rearrangement in the ALK or ROS1 genes. Brigatinib and binimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To determine the safety and tolerability of brigatinib in combination with binimetinib in stage IIIB or IV anaplastic lymphoma kinase (ALK) or ROS1 rearranged non-small cell lung cancer (NSCLC) and the recommended phase 2 dose.

SECONDARY OBJECTIVES:

I. To determine preliminary efficacy of brigatinib in combination with binimetinib in any line of treatment.

II. To characterize the pharmacokinetic parameters of brigatinib in combination with binimetinib.

EXPLORATORY OBJECTIVES:

I. To assess circulating tumor deoxyribonucleic acid (DNA) (ctDNA) utility in evaluating treatment response.

II. To evaluate the blockade of downstream signaling indicating response or resistance to treatment of immunohistochemistry (IHC) for phosphatidylinositol 3-kinase (PI3K)/Protein kinase B (AKT)/Mitogen-activated protein kinase (MAPK) pathway activity evaluation.

OUTLINE: This a dose-escalation study.

Patients receive brigatinib orally (PO) once daily (QD) and binimetinib PO twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days and then every 6 months for 12 months.

Brigatinib and Binimetinib in Treating Patients With Stage IIIB-IV ALK or ROS1-Rearranged Non-small Cell Lung Cancer

A Phase I Study of Brigatinib With Binimetinib in Advanced ALK- or ROS1-Rearranged Non-Small Cell Lung Cancer (NSCLC)

Evaluating the number and frequency of adverse events as determined by the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version (v)5.0 by investigator's assessment will be used to determine the recommended phase 2 dose for future studies.

A dose limiting toxicity (DLT) is generally defined as a grade 3 or higher, treatment-related adverse event that is attributable to the study treatment during the first 28 days of therapy (Cycle 1). The dose limiting toxicity will be based on the tolerability observed during cycle 1 of treatment/observation. Adverse events will be assessed by the investigators using NCI-CTCAE v5.0.

Treatment Emergent AEs will be defined by the NCI CTCAE v5.0 as AEs newly occuring after the patient has begun study treatment.

Severity grade will be defined by the NCI CTCAE v5.0.

RECIST v1.1 will be used to determine the overall response rate defined as participants with a complete response (CR) or a partial response (PR). Point estimate and 95% exact binomial confidence interval (CI) will be obtained for ORR.

Will be defined as maximal reduction in tumor size based on Response Evaluation Criteria in Solid Tumors (RECIST) measurement. Median and inter-quartile range will be used to describe the depth of response (the maximal reduction in tumor size based on RECIST measurement).

Plasma concentration assessment (pharmacokinetic data) of brigatinib during coadministration with binimetinib will be determined by assay at various timepoints. The assay will be done by Takeda / their designated vendor.

PFS is measured as the time from start of treatment to time of disease progression at 6 months. Kaplan-Meier method will be used to describe the describe the median PFS with 95% CI.

Overall Survival is measures as the time from start of treatment to time of death, or lost to follow-up. Kaplan-Meier method will be used to describe the describe the median OS at 12 months with 95% CI.

Takeda

Array BioPharma

University of California, San Francisco

Diseases and Abnormalities at or Before Birth

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Congenital Abnormalities

Lymphoma

Lymphosarcoma

Anti-Infective Agents

Everolimus

Sirolimus

Temsirolimus

MTOR Inhibitors

Ceritinib

Immunosuppressive Agents

Immunologic Factors

Patients receive ceritinib PO QD and everolimus PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

Pharmacological Study

George R Blumenschein

This phase I trial studies the side effects and best dose of ceritinib and everolimus in treating patients with solid tumors that have spread from where they started to nearby tissue or lymph nodes (locally advanced) or to other places in the body (metastatic) or stage IIIB-IV non-small cell lung cancer. Ceritinib and everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVE:

I. To determine the maximum tolerated dose (MTD) of ceritinib (novel, potent and selective small molecule anaplastic lymphoma kinase \[ALK\] inhibitor) in combination with everolimus (a mammalian target of rapamycin \[mTOR\] inhibitor) in advanced cancers.

SECONDARY OBJECTIVES:

I. Preliminary descriptive assessment of the anti-tumor activity (response rate) of the combination in advanced non-small cell lung cancer (NSCLC) based upon Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

II. To determine the pharmacokinetics of ceritinib and everolimus used in combination.

III. To determine the safety of ceritinib and everolimus used in combination. IV. To evaluate the toxicities and tolerability of the combinations. V. To document anti-tumor activity (disease control rate at 8 weeks and progression-free survival).

EXPLORATORY OBJECTIVES:

I. To explore baseline molecular markers that may predict clinical activity, and to explore pharmacodynamic markers in blood, tumor tissue and molecular imaging that may predict an increase in apoptosis and clinical activity.

II. To determine concordance of ALK (protein levels on immunohistochemistry, fusion detection by fluorescence in situ hybridization \[FISH\] and somatic mutations).

III. To determine ribosomal protein S6 kinase (S6K) phosphorylation as a measure of mTOR inhibition.

OUTLINE: This is a dose-escalation study.

Patients receive ceritinib orally (PO) once daily (QD) and everolimus PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 28 days.

Ceritinib and Everolimus in Treating Patients With Locally Advanced or Metastatic Solid Tumors or Stage IIIB-IV Non-small Cell Lung Cancer

A Phase I/Ib Dose Escalation and Biomarker Study of Ceritinib (LDK378) in Combination With Everolimus in Patients With Locally Advanced or Metastatic Solid Tumors With an Expansion in NSCLC Characterized by Abnormalities in Anaplastic Lymphoma Kinase (ALK) Expression

The specific arm is to evaluate whether biomarkers can be correlated with clinical benefit or used as potential markers of biological activity, therapeutic sensitivity, or resistance.

Evaluated based upon Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

Progression free survival will be analyzed.

Estimated and calculated using a noncompartmental pharmacokinetic model. Plasma concentrations and pharmacokinetic parameters for each drug dose will be summarized using descriptive statistics and the mean plasma concentrations for each drug dose will be plotted versus time.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Ensartinib

Single-arm trial whereby all consented, enrolled, eligible patients receive X-396 capsule, 225 mg once daily.

X-396 Capsule

Jinxiao Xu

Shun Lu

Shun Lu, Ph.D

To assess treatment effectiveness and safety of oral X-396 capsule (Ensartinib) administered to Chinese patients with Advanced Non-Small Cell Lung Cancer (NSCLC) that is confirmed to be positive for a c-ROS Oncogene (ROS1) positive gene mutation (translocation or inversion).

This is a phase II, multicenter, single-arm study in which the efficacy and safety of X-396 capsule (Ensartinib) will be assessed in adult Chinese patients with ROS1-positive (rearrangement or inversion) non-small cell lung cancer (NSCLC). Approximately 69 patients (59 for never-treated, and 10 for previously treated with crizotinib) with locally advanced or metastatic NSCLC carrying ROS1-rearrangement will be enrolled in the study.

X-396 Capsule in Advanced NSCLC Patients With ROS1 Gene Rearrangement

Phase II, Open-Label, Single Arm Study of the Efficacy and Safety of X-396 Capsule in Patients With ROS1 Positive Advanced NSCLC

ORR per RECIST 1.1 calculated as the proportion of patients with a best overall response defined as complete response (CR) or partial response (PR), based on IRC.

ORR per RECIST 1.1 calculated as the proportion of patients with a best overall response defined as CR or PR, based on investigator's assessment

DCR defined as the percentage of patients who have achieved CR, PR and stable disease (SD), based on RECIST 1.1 measured by IRC or investigator

iORR calculated as the ORR (CR+PR) of lesions in the brain for patients who have measurable disease in the brain at baseline.

PFS defined as time from first dose of X-396 capsule to disease progression or death due to any cause, based on RECIST 1.1.

TTP defined as time from first dose of X-396 capsule to disease progression, based on RECIST 1.1.

DOR defined as time from documentation of tumor response (CR or PR) to disease progression or death, based on RECIST 1.1

OS, defined as time from first dose of X-396 to death due to any cause.

The FACT-L questionnaire consisted of several major aspects of life (Physical, social/family, emotional, and functional well-being) as well as lung cancer subscale (symptoms, cognitive function, regret of smoking). Scores for item ranging from 0 (not at all) to 4 (very much).

Adverse events are graded according to CTCAE 4.03

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pembrolizumab, Lenvatinib and Chemotherapy After TKIs in NSCLC	NCT04989322	Nsclc EGFR Activating... EGF-R Positive ... ALK Gene Rearra... ROS1 Gene Rearr... ROS1 Positive N...	Pembrolizumab Lenvatinib Pemetrexed Carboplatin	18 Years -	The University of Hong Kong
Study of Crizotinib for ROS1 and MET Activated Lung Cancer	NCT04084717	Non-squamous No... Stage IV Non-sm... ROS1 Gene Rearr... MET Activating ... MET Amplificati...	Crizotinib	18 Years -	University Health Network, Toronto
REPotrectinib in ROS1-positive Non-small Cell Lung Cancer Patients With Active Brain mEtastasis	NCT06315010	NSCLC Brain Metastase... ROS1 Gene Rearr...	Repotrectinib	18 Years -	MedSIR
Pembrolizumab, Lenvatinib and Chemotherapy After TKIs in NSCLC	NCT04989322	Nsclc EGFR Activating... EGF-R Positive ... ALK Gene Rearra... ROS1 Gene Rearr... ROS1 Positive N...	Pembrolizumab Lenvatinib Pemetrexed Carboplatin	18 Years -	The University of Hong Kong
Brigatinib and Binimetinib in Treating Patients With Stage IIIB-IV ALK or ROS1-Rearranged Non-small Cell Lung Cancer	NCT04005144	ALK Gene Rearra... Lung Non-Small ... Progressive Dis... ROS1 Gene Rearr... Stage IIIB Lung... Stage IIIC Lung... Stage IV Lung C... Stage IVA Lung ... Stage IVB Lung ...	Binimetinib Brigatinib	18 Years -	University of California, San Francisco
Ceritinib and Everolimus in Treating Patients With Locally Advanced or Metastatic Solid Tumors or Stage IIIB-IV Non-small Cell Lung Cancer	NCT02321501	ALK Positive Locally Advance... Metastatic Mali... ROS1 Gene Rearr... Stage IIIB Lung... Stage IV Lung N...	Ceritinib Everolimus Laboratory Biom... Pharmacological...	18 Years -	M.D. Anderson Cancer Center
Brigatinib and Binimetinib in Treating Patients With Stage IIIB-IV ALK or ROS1-Rearranged Non-small Cell Lung Cancer	NCT04005144	ALK Gene Rearra... Lung Non-Small ... Progressive Dis... ROS1 Gene Rearr... Stage IIIB Lung... Stage IIIC Lung... Stage IV Lung C... Stage IVA Lung ... Stage IVB Lung ...	Binimetinib Brigatinib	18 Years -	University of California, San Francisco
X-396 Capsule in Advanced NSCLC Patients With ROS1 Gene Rearrangement	NCT03608007	Lung Cancer ROS1 Gene Rearr...	X-396 Capsule	18 Years -	Betta Pharmaceuticals Co., Ltd.

Spots Global Cancer Trial Database for ros1 gene rearrangement