Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Hematologic Neoplasms

Lymphoma, B-Cell

Lymphosarcoma

B-cell Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Ceritinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Ceritinib was dosed on a flat scale of 750 mg (e.g., 5 x 150 mg capsules) orally, once daily, on a continuous dosing cycle. A complete treatment cycle was defined as 28 days with no breaks between dosing cycles.

Ceritinib was dosed on a flat scale of 750 mg (e.g., 5 x 150 mg capsules) orally,once daily, on a continuous dosing cycle. A complete treatment cycle was defined as 28 days. There were no breaks between dosing cycles.

The purpose of this signal seeking study was to determine whether treatment with ceritinib demonstrated sufficient efficacy in select pathway-activated solid tumors and/or hematologic malignancies to warrant further study.

This was an open label study to determine the efficacy and safety of treatment with ceritinib in patients with a diagnosis of solid tumors or hematological malignancies that had been pre-identified (prior to study consent) to have ALK or ROS1 positive mutations, translocations, rearrangements or amplifications and whose disease had progressed on or after standard treatment. The study consisted of a treatment phase where all patients received ceritinib capsules for a total dose of 750 mg daily for up to 8 cycles of 28 days. Disease assessments for clinical benefit were performed every 8 weeks until disease progression or end of treatment. Following discontinuation of treatment for any reason, patients were followed for safety for 30 days. Survival information was collected every 3 months until 2 years after the last patient had enrolled into the study. Study was amended to allow for discontinuation of survival period if primary endpoint was not met.

Study was terminated due to low enrollment.

Ceritinib (LDK378) for Patients Whose Tumors Have Aberrations in ALK or ROS1 (SIGNATURE)

Modular Phase II Study to Link Targeted Therapy to Patients With Pathway Activated Tumors: Module - 7 Ceritinib (LDK378) for Patients Whose Tumors Have Aberrations in ALK or ROS1

Solid tumors were assessed using RECIST 1.1 criteria and included responses of complete response (CR) or partial response (PR) or stable disease (SD). For hematologic tumors, other hematological response criteria applied. CR=disappearance of all target lesions. Pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10mm. PR=at least 30% decrease in sum of diameters of target lesions from baseline sum diameters. SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. Progressive disease (PD)=at least a 20% increase in sum of diameter of measured target lesions from smallest sum of diameter of all target lesions recorded at or after baseline (sum must also demonstrate an absolute increase of at least 5mm). One or more new lesions was considered PD. Overall response rate (ORR) = (CR + PR). Clinical benefit rate = (CR + PR + SD)

For patients with solid tumors the assessment criteria was RECIST 1.1 and included responses of complete response (CR) or partial response (PR) or stable disease (SD). For hematologic tumors, other hematological response criteria applied. CR=disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10mm. PR=at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. Progressive disease (PD)=at least a 20% increase in sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline (sum must also demonstrate an absolute increase of at least 5mm). One or more new lesions was also considered progression.

Progression-free survival (PFS) was the time from the date of start of study drug to the date of event defined as the first documented progression or death due to any cause within 30 days of the last dose. If a patient has not had an event, progression-free survival was censored at the date of last adequate tumor assessment.

Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause

Duration of response (DOR) is defined as time from the first documented response (CR or PR) to the date first documented disease progression or relapse or death due to any cause

Novartis Pharmaceuticals

AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment

Ceritinib 750 mg

≥65 - < 75

≥75

Age, Customized

Female Able to bear children

Female Premenarche

Female Postmenopausal

Female Sterile of child bearing age

Male

Sex/Gender, Customized

Caucasian

Black

Asian

Native American

Other

Race/Ethnicity, Customized

Ampullary adenocarcinoma

Appendix

Breast

Central nervous system

Cervix

Colorectal cancer

Gastroesophageal junction

Head and neck squamous cell carcinoma

Liver

Lung non-small cell adenocarcinoma

Neuroendocrine

Ovarian

Pancreas

Prostate

Sarcoma

Skin non-melanoma

Uterus

Uveal Melanoma

Number of participants with primary type of tumor

Participants with primary tumor type (sponsor adjudicated)

Study Director

ORR (CR + PR) for all patients

CBR (CR + PR + SD) for all patients

ORR (CR + PR) for colorectal cancer patients

CBR (CR + PR + SD) for colorectal cancer

ORR and CBR was reported for all patients and for a subgroup of patients with colorectal cancer

Percentage of Participants Overall Response Rate (ORR) and Clinical Benefit Rate (CBR) Utilizing RECIST 1.1 at Approximately 16 Weeks

Complete response - all patients

Partial response - all patients

Stable disease- all patients

Progressive disease - all patients

Non-evaluable - all patients

Stable disease - Colorectal cancer patients

PD - Colorectal cancer patients

Non-evaluable - Colorectal cancer patients

tumor response was reported for all patients and for a subgroup of patients with colorectal cancer

Number of Participants With Tumor Responses Utilizing RECIST 1.1 at Approximately 16 Weeks

All patients

Colorectal cancer patients

reported for all patients and for a subgroup of patients with colorectal cancer

Progression-Free Survival (PFS)

1 Month

2 Month

3 Month

4 Month

5 Month

6 Month

9 Month

12 Month

18 Month

24 Month

30 Month

1 Month Colorectal cancer patients

2 Month Colorectal cancer patients

3 Month Colorectal cancer patients

4 Mongth Colorectal cancer patients

5 Month Colorectal cancer patients

6 Month Colorectal cancer patients

9 Month Colorectal cancer patients

Percentage of Participants With Progression-Free Survival (PFS) - Kaplan-Meier Estimates

Deaths due to study indication

Deaths due to study indication while on treatment

Overall Survival (OS) - Number of Participant Deaths

One Patient with PR

Second Patient with PR

only 2 patients met criteria for duration of response

Duration of Response (DOR)

Total deaths

Deaths on treatment

On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 27 months (treatment duration ranged from 0.2 to 25.9 months). Deaths post treatment survival follow up were collected after the on treatment period, up to approximately 39 months.

Clinical Database Population: All treated patients

All Collected Deaths

Overall Study

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Slides containing breast cancer paraffin embedded tissue sections.

Sheila Dobin, Ph.D.

The purpose of the study is the identification of amplification level in human breast tissue. The imaging system is intended for diagnostic use as an aid to the pathologist in the detection, counting and classification of Her2 FISH stained tissue samples.

Detection of Amplification of Her2 Fluorescent in Situ Hybridization (FISH) in Breast Tissue Sections

Concordance Study for Amplification Detection of Her2 FISH in Breast Tissue Sections

Applied Spectral Imaging Ltd.

Tsafrir Kolatt

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Digestive System Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Leukemia

Melanoma

Thyroid Neoplasms

Thyroid Diseases

Gastrointestinal Stromal Tumors

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Head and Neck Neoplasms

Myeloid Leukemia

Acute Myeloid Leukemia

Ovarian Cancer

Ovarian Epithelial Cancer

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Dovitinib (TKI) will be dosed on a flat scale of 500 mg on a 5 days on/2 days off dosing schedule.

Dovitinib (TKI258)

The purpose of this signal seeking study was to determine whether treatment with dovitinib (TKI258) demonstrated sufficient efficacy in select pathway-activated solid tumors and/or hematologic malignancies to warrant further study.

This was a phase II, open label study to determine the efficacy and safety of treatment with dovitinib (TKI258) in patients with a diagnosis of select solid tumors or hematological malignancies that have been pre-identified (prior to study consent) to have mutations, translocations or amplifications and whose disease has progressed on or after standard treatment.

Genomic profiling is becoming more accessible to patients and their physicians. As such, more patients have been identified with potentially-actionable mutations, translocations or amplifications but do not have access to targeted drug treatment. This is a signal-seeking study to match patients with tumor pathway activations inhibited by dovitinib to the RTK inhibitor dovitinib. Pre-identification of mutations, translocations, or amplifications will be performed locally at a CLIA certified laboratory prior to participation on the trial.

For the purpose of this study, genomic profiling is not considered part of screening. Informed consent must be signed before any screening activities take place. Once eligibility (screening criteria met) has been confirmed by Novartis, the patient will initiate therapy with dovitinib single-agent. The patient may not receive any additional anti-cancer therapy during treatment with dovitinib.

Patients received study treatment until disease progression (assessed by investigator per RECIST 1.1 or appropriate hematologic response criteria), unacceptable toxicity, death or discontinuation from study treatment for any other reason (e.g., withdrawal of consent, start of a new anti-neoplastic therapy or at the discretion of the investigator), otherwise known as End of Treatment. All patients who discontinue from study treatment due to disease progression must have their progression clearly documented.

Disease assessment (by RECIST 1.1 or appropriate hematological response criteria) will be performed every 8 weeks (±4 days) after first dose of study drug (Day 1 of every odd cycle), until disease progression or end of treatment, whichever occurs first. The frequency of disease assessment may be reduced to every 12 weeks for patients who have at least 4 post-baseline disease assessments and are clinically stable (except AML patients). Scans was assessed locally by the investigator. After discontinuation of treatment, patients, regardless of reason for treatment discontinuation, will be followed for safety for 30 days after the last dose.

All patients will be followed for survival status every 3 months for 2 years after the last patient has enrolled in the study,regardless of treatment discontinuation reason (except if consent is withdrawn or patient is lost to follow-up)

Dovitinib for Patients With Tumor Pathway Activations Inhibited by Dovitinib

Modular Phase II Study to Link Targeted Therapy to Patients With Pathway Activated Tumors: Module 2 - Dovitinib for Patients With Tumor Pathway Activations Inhibited by Dovitinib Including Tumors With Mutations or Translocations of FGFR, PDGFR, VEGF, cKIT, FLT3, CSFR1, Trk and RET

CBR determined by investigator assessment for each tumor assessment \& defined as responses of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) ≥ 16 wks. Confirmed CR/PR or SD prior to 16 wks,but discontinued prior to 16 wks for reasons other than progressive disease,will have their clinical benefit defined non-evaluable; confirmed CR/PR or SD prior to 16 wks,but progressed prior to 16 wks,will be considered not achieving clinical benefit;if CR/PR/SD occurred prior to 16 wks,but progressed at or after 16 wks without evidence of CR/PR/SD at or after 16 wks,will also be considered not achieving clinical benefit. CBR will be analyzed by comparing achieved CBR with a historical control rate of each tumor type,\& if there is at least 90% probability that the response rate in a tumor type exceeds the historical rate,then the tumor type will be considered a success. CBR: CR+PR+SD the assessment criteria was RECIST 1.1

Overall Response (OR) of Partial Response (PR) or greater based on local investigator assessment. For patients with solid tumors, the assessment criteria will be RECIST 1.1 and will include responses of CR and/or PR. For hematologic tumors other appropriate hematological response criteria will apply and are included in the appendices. ORR: CR+PR

Progression free survival (PFS) is defined as the time from the date of first dose to the date of first documented disease progression or relapse or death due to any cause.

Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause. If a patient is not known to have died, survival time will be censored at the date of the last contact

TKI258

Age, Continuous

Sex: Female, Male

Complete response (CR)

Partial response (PR)

Stable disease (SD)

Clinical benefit rate (CBR)

Full Analysis Set (FAS) included all patients who received at least one dose of study drug.

FAS was used for the analysis of efficacy endpoints.

Clinical Benefit Rate (CBR)

Overall response rate (ORR)

Overall Response (OR) of Partial Response (PR) or Greater

Overall Survival (OS)

Fulvestrant

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Antineoplastic Agents, Hormonal

Hormones

Hormone Antagonists

In adult patients with advanced solid malignancies whose tumors have an alteration (mutation or amplification) of the PIK3CA gene, and in patients whose tumors are have wild-type PIK3CA gene

In post-menopausal patients with estrogen receptor positive locally advanced or metastatic breast cancer whose tumors have an alteration of the PIK3CA gene, and in patients whose tumors are have wild-type PIK3CA gene

BYL719 is an oral α-specific phosphatidylinositol-3-kinase (PI3K) inhibitor.

BYL719

In adult patients with advanced solid malignancies whose tumors have an alteration (mutation or amplification) of the PIK3CA gene.

Fulvestrant is an estrogen receptor antagonist, administered by monthly intramuscular injection

This is a first-in-man trial, in which BYL719 will be administered to adult patients with advanced solid tumors, whose tumors have an alteration of the PIK3CA gene and whose disease has progressed despite standard therapy or for whom no standard therapy exists. A combination of BYL719 with fulvestrant will also be investigated in post-menopausal patients with locally advanced or metastatic breast cancer whose tumors have an alteration of the PIK3CA gene. The single agent MTD dose expansion cohort and the fulvestrant combination MTD dose expansion cohort will also include ER+/HER2- breast cancer patients whose tumors have the wild type PIK3CA gene

A Study of BYL719 in Adult Patients With Advanced Solid Malignancies, Whose Tumors Have an Alteration of the PIK3CA Gene

A Phase IA, Multicenter, Open-label Dose Escalation Study of Oral BYL719, in Adult Patients With Advanced Solid Malignancies, Whose Tumors Have an Alteration of the PIK3CA Gene

MTD (or RP2D) of oral BYL719 as single agent and in combination with fulvestrant.

Safety and tolerability: type, intensity, severity and seriousness of adverse events (AE) according to NCI CTCAE v. 4.0.

Objective tumor response rate (ORR), defined as the sum of complete response and partial response as best reported response by RECIST 1.0 criteria (Novartis v2.0 guideline)

Diseases and Abnormalities at or Before Birth

Congenital Abnormalities

Biliary Tract Cancer

Group 1: Urothelial cancer with HER2 or HER3 mutation Group 2: Biliary tract cancer with HER2 or HER3 mutation Group 3: Breast cancer with HER2 or HER3 mutation Group 4: Breast cancer with HER2 amplification or overexpression as per American Society of Clinical Oncology - College of American Pathologists (ASCO-CAP) 2013 guidelines Group 5: Non-small cell lung cancer (NSCLC) with HER2 or HER3 mutation Group 6: Colorectal cancer (CRC) with HER2 mutation or amplification Group 7: Other tumors with HER2 or HER3 mutation, amplification, or overexpression (eg, gastric or gastroesophageal junction (GEJ), endometrial)

TAS0728 is an oral HER2 covalent inhibitor investigated in patients with advanced solid tumor harboring HER2 or HER3 abnormalities. It will be administered orally at a starting dose of 50 mg BID each morning and evening and escalated to the DLT. The MTD will be used for the phase 2 arms of the study.

TAS0728

This is a First-in-Human (FIH), 2-part, Phase 1/2, open-label, multicenter study design to evaluate the safety, tolerability, PK, pharmacodynamics, PGx, and efficacy of TAS0728. This study consists of Phase 1 and Phase 2 components in subjects with advanced solid tumors with HER2 or HER3 overexpression, amplification, or mutation who have progressed despite standard therapy or for which no standard therapy exists, particularly urothelial cancer, biliary tract cancer, metastatic breast cancer, non-small cell lung cancer and colorectal cancer.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Ceritinib (LDK378) for Patients Whose Tumors Have Aberrations in ALK or ROS1 (SIGNATURE)	NCT02186821	Tumors With Abe...	Ceritinib	18 Years -	Novartis
Detection of Amplification of Her2 Fluorescent in Situ Hybridization (FISH) in Breast Tissue Sections	NCT01066507	Breast Cancer		21 Years -	Applied Spectral Imaging Ltd.
Dovitinib for Patients With Tumor Pathway Activations Inhibited by Dovitinib	NCT01831726	Tumor Pathway A...	Dovitinib (TKI2...	18 Years - 100 Years	Novartis
A Study of BYL719 in Adult Patients With Advanced Solid Malignancies, Whose Tumors Have an Alteration of the PIK3CA Gene	NCT01219699	Advanced Solid ... Estrogen Recept...	BYL719 Fulvestrant	18 Years -	Novartis
A Study of TAS0728 in Patients With Solid Tumors With HER2 or HER3 Abnormalities	NCT03410927	Advanced Solid ... Advanced Solid ...	TAS0728	18 Years -	Taiho Oncology, Inc.
A Study of BYL719 in Adult Patients With Advanced Solid Malignancies, Whose Tumors Have an Alteration of the PIK3CA Gene	NCT01219699	Advanced Solid ... Estrogen Recept...	BYL719 Fulvestrant	18 Years -	Novartis
Efficacy and Safety of AZD4547 Versus Paclitaxel in Patients With Advanced Gastric or Gastro-oesophageal Cancer	NCT01457846	Gastro-oesophag... Gastric Cancer	AZD4547 paclitaxel	25 Years - 130 Years	AstraZeneca
Study of the RNR Inhibitor BBI-825 in Subjects With Tumors With Resistance Gene Amplifications	NCT06299761	Solid Tumor	BBI-825	18 Years - 99 Years	Boundless Bio
Futibatinib in Patients With Specific FGFR Aberrations	NCT04189445	Advanced or Met... Advanced or Met... Myeloid or Lymp...	Futibatinib	18 Years -	Taiho Oncology, Inc.

Spots Global Cancer Trial Database for amplification