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

Digestive System Diseases

Stomach Neoplasms

Stomach Cancer

Futibatinib

Advanced or metastatic solid tumors harboring FGFR1-4 rearrangements

Advanced or metastatic solid gastric or GEJ cancer harboring FGFR2 amplification

Myeloid or lymphoid neoplasm harboring FGFR1 rearrangement

Futibatinib tablets will be dosed orally every day on a continuous 28-day cycle

The purpose of this study is to evaluate the efficacy and safety of futibatinib in patients with FGFR aberrations in 3 distinct cohorts. Patients will be enrolled into one of 3 cohorts: patients with advanced, metastatic or locally-advanced solid tumors harboring FGFR1-4 rearrangements (excluding primary brain tumors and intrahepatic cholangiocarcinoma \[iCCA\]); patients with gastric or gastro-esophageal junction (GEJ) cancer harboring FGFR2 amplification; and patients with myeloid or lymphoid neoplasms with FGFR1 rearrangements.

Study TAS-120-202 is an open-label, multinational, 3-arm Phase 2 study evaluating the efficacy, safety, tolerability, PK, and pharmacodynamics of futibatinib in patients with FGFR aberrations. Eligible patients will be assigned to 1 of 3 treatment cohorts based on diagnosis and FGFR gene aberration status.

Patients will receive futibatinib at an oral dose of 20 mg once a day on a continuous 28-day cycle.

The study will enroll approximately:

* Cohort A: 60 patients with locally advanced, advanced, or metastatic solid tumor harboring FGFR rearrangements other than primary brain tumor or iCCA;
* Cohort B: 35 patients with locally-advanced, advanced, or metastatic gastric cancer or gastro-esophageal junction (GEJ) with FGFR2 amplification;
* Cohort C: 20 patients with myeloid or lymphoid neoplasms (MLN) with FGFR1 rearrangements

Treatment in all cohorts will continue until disease progression, unacceptable toxicity, or any other of the criteria for treatment discontinuation is met. For patients who discontinue treatment for reasons other than disease progression, tumor assessments should be continued until radiologic disease progression is documented or until initiation of subsequent new anticancer therapy (whichever occurs first).

Patients will be followed for survival every 12 weeks (±2 weeks) until survival events (deaths) have been reported for 75% of enrolled patients or the study is terminated early by the Sponsor.

Additional cohorts may be added in the future in case of new emerging efficacy data.

The study consists of independent 3 cohorts (Cohorts A, B and C) and there is no difference in the treatment regimen between the cohorts

Futibatinib in Patients With Specific FGFR Aberrations

A Phase 2 Study of Futibatinib in Patients With Specific FGFR Aberrations

ORR, defined as the proportion of patients experiencing a best overall response of partial response (PR) or complete response (CR) (per Response Evaluation Criteria in Solid Tumors, RECIST version 1.1), based on independent central review of radiological images.

CR rate, defined as the proportion of patients who achieved a CR (per response criteria for MLN) based on investigators' assessment of imaging, peripheral blood, and bone marrow.

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

DOR, defined as the time from the first documentation of response (CR or PR in Cohorts A and B; CR, PR, or CRi in Cohort C) to the first documentation of objective tumor progression or death due to any cause, whichever occurs first.

PFS, defined as the time from first dose of the study therapy to the date of death (any cause) or disease progression, whichever occurs first.

OS, defined as the time from the date of first dose to the death date.

DCR, defined as the proportion of patients experiencing a best overall response of stable response (SD), PR, or complete response (CR) (per RECIST 1.1).

CR+CRi rate, defined as the proportion of patients who achieved a CR or CRi

Duration of CR, defined as the time from the first documentation of CR to the first documentation of recurrence or death due to any cause, whichever occurs first.

Duration of CR+CRi, defined as the time from the first documentation of CR or CRi to the first documentation of disease relapse or death due to any cause, whichever occurs first.

CCyR rate, defined as the proportion of patients who achieved a CCyR

PCyR rate, defined as the proportion of patients who achieved a PCyR

RFS, defined as the time from first documentation of CR to the date of death (any cause) or disease relapse or death due to any cause, whichever occurs first

EFS, defined as the time from first dose of study therapy to treatment failure, disease relapse after CR, or patient death due to any cause, whichever occurs first

Safety based on reported AEs will be graded according to the National Cancer Institute- Common Terminology Criteria for Adverse events (NCI-CTCAE), Version 5.0.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Ceritinib (LDK378) for Patients Whose Tumors Have Aberrations in ALK or ROS1 (SIGNATURE)	NCT02186821	Tumors With Abe...	Ceritinib	18 Years -	Novartis
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 rearrangement