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

Heart and Blood Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

KTX-1001 will be administered orally, daily for 28 days.

KTX-1001

Soo Bang

Sanjana Miskin

Peter Bergsagel, MD

Daniel Duarte

Alfred Chung, MD

Benjamin Sun

Vivek Roy, MD

Justin Guidry

Sagar Lonial, MD, FACP

Hafsa Ahmed

Al-Ola Abdallah, MD

Lisa Bogart

Andrew Yee, MD

Alicia Marggraf

David Dingli, MD, PhD

Thomas Nelson

David S Siegel, MD, PhD

Adolfo Aleman

Saad Usmani, MD

Leah Gilbert

Saad Usmani, MD, MBA, FACP

Cristina Gasparetto, MD

Heather Griffith

Jesus Berdeja, MD

Sarah Ladd

Aimaz Afrough, MD

Silviya Meletath

Suzanne Trudel, MSc, MD

Saima Dean

Cyrille Touzeau, MD

Laetitia Mallard

Pierre Bories, MD

Alicia Perez

Paula Rodriguez, MD, PhD

Joana Sofia Reis de Carvlaho

Laura Rosinol, MD

Veronica Martil

Laura Rosinol, MD, PhD

Maria-Victoria Mateos Manteca, MD, PhD

Magdalena Garcia Astorga

A Phase I study to evaluate the safety of a novel, orally available, selective, and potent small molecule inhibitor of the histone lysine methyl transferase MMSET (also known as NSD2/WHSC1) to prevent the dimethylation of H3K36 in adult patients with relapsed or refractory multiple myeloma (RRMM).

This is a Phase I, open-label, dose escalation and expansion study in adult patients with RRMM.

In the dose escalation phase (Part A), patients will be evaluated for DLTs during Cycle 1 (28 days). The KTX-1001 MTD, RP2D, and schedule will be determined.

In the dose expansion phase (Part B), patients with translocation t(4;14) or a GOF mutation in MMSET (eg, E1099K) will be enrolled. Patients will receive KTX-1001 at the RP2D to further define safety and tolerability and provide preliminary efficacy information.

A Study of an MMSET Inhibitor in Patients With Relapsed and Refractory Multiple Myeloma

A Phase 1 Study of KTX-1001, an Oral, First-In-Class, Selective, and Potent MMSET Catalytic Inhibitor That Suppresses H3K36me2 in Patients With Relapsed and Refractory Multiple Myeloma

Treatment-emergent adverse events (AEs), treatment-related AEs, and clinically significant changes in laboratory test results will be evaluated

Per IMWG Consensus Criteria for Response and Minimal Residual Disease Assessment in Multiple Myeloma

K36 Therapeutics, Inc.

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
A Study of an MMSET Inhibitor in Patients With Relapsed and Refractory Multiple Myeloma	NCT05651932	Multiple Myelom... Myeloma Myeloma Multipl...	KTX-1001	18 Years -	K36 Therapeutics, Inc.

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