Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Endometrial Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Ovarian Cancer

Ovarian Epithelial Cancer

SC-004

ABBV-181

AbbVie Inc.

This is a two-part study consisting of Part A (dose regimen finding) followed by Part B (dose expansion). Part A (dose regimen finding) will allow definition of the maximum tolerated dose (MTD) through dose escalation and possible dose interval modification. In Part B (dose expansion), potential therapeutic doses may be studied with SC-004 as monotherapy and SC-004 in combination with ABBV-181 in disease-specific cohorts.

SC-004 Alone or With ABBV-181 in Subjects With Epithelial Ovarian, Fallopian Tube, Primary Peritoneal and Endometrial Cancers

An Open Label, Phase 1 Study of SC-004 as Monotherapy and in Combination With ABBV-181 in Subjects With Epithelial Ovarian, Including Fallopian Tube and Primary Peritoneal and Endometrial Cancers

DLTs graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.

Observed plasma concentrations at trough.

OS is defined as the time from the subject's first dose date to death due to any cause.

ORR is defined as the proportion of subjects with complete response or partial response (CR+PR).

CBR is defined as the proportion of subjects with an objective response or stable disease (CR+PR+SD).

PFS time is defined as the time from the subject's first dose of study drug (Day 1) to either the subject's disease progression or death due to any cause, whichever occurs first. Under the situation that neither event occurs, the PFS time will be censored at the date of last tumor assessment. Subjects lacking an evaluation of tumor response after their first dose of study treatment will have their event time censored at Day 1.

DOR is defined as the time from the subject's initial objective response (CR or PR) to study drug therapy to disease progression or death due to any cause, whichever occurs first. If the dates of disease progression or death are not available, the DOR will be censored at the date of last valid tumor assessment.

Area under the plasma concentration-time curve within a dosing interval.

QT interval measurement corrected by Fridericia's formula (QTcF).

DOCB is defined as the time from a subject's objective response (CR or PR) or stable disease (SD) to study drug therapy to disease progression or death due to any cause whichever occurs first.

AbbVie

Digestive System Diseases

Stomach Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Stomach Diseases

Stomach Cancer

SC-007 intravenous (IV) (various doses and dose regimens)

SC-007

This is a multicenter, open-label, Phase 1 study in participants with colorectal cancer (CRC) or gastric cancer to study the safety and tolerability of SC-007 and consists of Part A (dose regimen finding) in participants with CRC followed by Part A in participants with gastric cancer. Part B (dose expansion) will enroll participants into separate disease specific cohorts of CRC or gastric cancer.

A Study of SC-007 in Subjects With Advanced Cancer

An Open Label Study of SC-007 in Subjects With Advanced Cancer

CBR is defined as the proportion of participants with an objective response or stable disease (CR+PR+SD).

PFS time is defined as the time from the participant's first dose of study drug (Day 1) to either the participant's disease progression or death due to any cause.

Observed plasma concentrations at trough of SC-007

OS is defined as the time from the participant's first dose date to death due to any cause.

ORR is defined as the proportion of participants with complete response or partial response (CR+PR)

DOR is defined as the time from the participant's initial objective response (CR or PR) to study drug therapy, to disease progression or death due to any cause, whichever occurs first.

Area under the plasma concentration-time curve within a dosing interval of SC-007

QT interval measurement corrected by Fridericia's formula (QTcF)

Maximum observed serum concentration of SC-007

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

Carcinoma, Hepatocellular

Multiple Myeloma

Neoplasms, Plasma Cell

Carcinoma

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Liver Neoplasms

Liver Diseases

Single group with 5 dose escalation for each cohort (0,5 mg/kg; 1 mg/kg; 2 mg/kg; 3 mg/kg; 5 mg/kg)

LNA-i-miR-221, IV daily infusion on days 1-4 followed by 24 days washout (1 cycle lasting 28 days)

LNA-i-miR-221

Pierfrancesco Tassone, MD

The LNA-i-miR-221 Phase I trial has been designed as a monocentric open label dose escalation study which received written approval by the Competent Authority and independent Ethics Committee (IEC). LNA-i-miR-221 will be investigated for safety and tolerability in patients, men and women age ≥18 yrs, affected by Refractory-MM and advanced solid tumors.

The LNA-i-miR-221 Phase I trial is a no-profit fully academic study on research funds and no external sponsor does exist. The study is a monocentric, open-label, phase I dose-finding to determine the safety, the maximum tolerated dose (MTD), and the recommended phase II dose of LNA-i-miR-221 (RP2D) using escalating doses; The secondary endopoints will be plasma and urinary pharmacokinetc (PK), efficacy as preliminary exploration of the antitumor activity, the disease control and the evaluation of biomonitoring activity. The study will include refractory MM and advanced solid tumors. In the last cohort, if 3 out of 3 or 5 out of 6 subjects do not experience DLT, no further dose escalation will be required and dose level 5 will be declared the MTD. At the end, further expansion will be performed to define RP2D, after a critical evaluation of trial data by SRC. LNA-i-miR-221 is a 13-mer antisense miR-221 inhibitor, which takes advantage of locked nucleic acid (LNA) technology and phosphorotioate (PS) backbone chemistry to increase affinity for miR-221 and nuclease resistance and represents a new frontier for chemically modified antisense oligonucleotides.

Participants will be assigned to 5 different cohorts, according to 5 different dose levels used. The cohorts will be defined with progressive numbers (1, 2, 3, 4, 5). Each cohort will be composed of 3 to 6 subjects. The dose level of LNA-i-miR-221 will be increased from one cohort to the next one. Independently from the assigned dose level, patients from each cohort will receive a total of 4 IV administrations as boluses. The treatment cycle will last 28 days. Each subject who will not experience any DLT (see DLT definition) will remain on the assigned dose level. In the case that MTD will be defined by the occurrence of DLT at the superior level, the MTD cohort will be considered for expansion to definitely assess the RP2D studies.

The treatment schedule (as amended and approved by AIFA on 1/15/2020) will be IV daily infusion on days 1-4 followed by 24 days washout (1 cycle lasting 28 days) with a modified 3+3 Fibonacci dose escalation design, with 5 different dose levels for each cohort (0,5 mg/kg; 1 mg/kg; 2 mg/kg; 3 mg/kg; 5 mg/kg), for safety and toxicity evaluation, MTD assessment, PK and modulatory activity investigation in refractory MM and advanced solid cancer patients. No other investigational drug and/or standard antitumor chemotherapy will be allowed during the study.

The enrolled subject will require hospitalization to ensure adequate protocol adherence.

LNA-i-miR-221will be administered inpatient setting as intravenous infusion of 30 minutes. During infusion and the following two hours post infusion, patients will be continuously monitored for vital signs. Local healthy authority guidelines must be followed with regard to further observation and monitoring, if applicable. Following the first infusion, patients will be observed for at least 120 minutes for fever, chills, or other infusion-associated symptoms. If prior infusions were well tolerated (without any signs or symptoms of infusion reactions) subsequent doses of LNA-i-miR-221 will be administered in 30 minutes with a 120 minutes observation period after infusion.

The determination of LNA-i-miR-221 in human plasma and urine will be used for the pharmacokinetic evaluation. For each enrolled subject, 2-5 ml of blood samples will be drawn for the quantification of LNA-i-miR-221 before, after 15 min and at the end of infusion at the following time points: 0.5, 1, 2, 4, 6, 12 hours on days 1 and 2. On day 3 and 4, blood samples will be drawn before and at the end of infusion at the following time points: 1, 2, 4. At 24 hours (day 5) and 48 hours (day 6) after last administration blood samples will be drawn for the quantification of LNA-i-miR-221.

Urine pharmacokinetic samples (15-20 ml) will be collected at pre-dose and 6, 12 and 24 hours period postdose on day 1 of cycle of treatment. Aliquots (15-20 ml) of 24-hour urine will also be collected at post dosing time during the cycle of treatment (day 2, 3, 4 and 5).

The vials containing lyophilized LNA-i-miR-221 must be stored at +2-8°C, while the reconstituted solution must be manipulated rapidly in a safe and secure place below 25°C, with no access for unauthorized personnel. The solution can be reconstituted immediately before administration. All adverse events will be followed with appropriate medical management until resolved. Patients removed from study for unacceptable adverse events will be followed until resolution or stabilization of the adverse event. For selected adverse events for which administration of the investigational drug was stopped, a rechallenge of the subject with the investigational drug may be conducted if considered both safe and ethical by the study coordinator.

All the safety data will be reviewed by an independent Safety Review Committee (SRC). Dose escalation to the next dose level will be allowed by SRC. In the last cohort, if 3 out of 3 or 5 out of 6 subjects do not experience DLT, no further dose escalation will be required and dose level 5 will be declared the MTD. At the end, further expansion will be performed to define RP2D, after a critical evaluation of trial data by SRC. At 30 (+/-1) days from the first dose of treatment, each enrolled patients will be evaluated for the end of treatment (EOT) visit in order to evaluate the efficacy and clinical benefit of LNA-i-miR-221 treatment based on RECIST V1.1 criteria. Only for patients with clinical benefit or radiological response/stable disease, the treatment will be offered until disease progression or if the patient withdraws consent. Out patients follow up will be continued every two months, until death.

Back-up blood samples will be collected for re-analysis in case of failure of the test measurement or for samples lost in transit. The samples will be appropriately stored and destroyed at study closure. Monitoring and auditing procedures defined/agreed by the External board (Sequre s.r.l. and Kilimo s.r l.) will be followed, in order to comply with GCP guidelines. This will include on-site checking of the case report forms (CRF) for completeness and clarity, cross-checking with source documents, and clarification of administrative matters.

Primary endpoints:

* To determine the safety, the maximum tolerated dose (MTD) and the RP2D of LNA-i-miR-221 using escalating doses in refractory multiple myeloma (MM) and advanced solid tumors for further investigations.
* To assess the safety and toxicity of LNA-i-miR-221

Secondary endpoints:

* PK analysis
* To preliminary explore the antitumor activity, the disease control, and the efficacy
* Biomodulatory activity A minimum/maximum number of 15/36 subjects will be enrolled in the study, according to expansion cohorts. All clinical data will be inserted on the Case Report Form (CRF) pages and all data can be extracted for the purpose of the ongoing analysis of the SRC and for statistical analysis.

monocentric, open label, phase I dose-escalation to determine the safety, the maximum tolerated dose (MTD) and the recommended phase II dose of LNA-i-miR-221 (RP2D) in a minimum/maximum number of 15/36 subjects affected by MM and advanced solid tumors. LNA-i-miR-221 will be administered IV daily infusion on days 1-4 followed by 24 days washout (1 cycle lasting 28 days) with a modified 3+3 Fibonacci dose escalation design, with 5 different dose levels for each cohort (0,5 mg/kg; 1 mg/kg; 2 mg/kg; 3 mg/kg; 5 mg/kg).

A Dose Escalation Study of LNA-i-Mir-221 for Cancer Treatment

A Dose Escalation Phase I Study of LNA-i-miR-221 for the Treatment of Refractory Multiple Myeloma and Advanced Solid Tumors

To assess the safety and toxicity of LNA-i-miR-221

The maximum tolerated dose (MTD) is the dose level below the dose level at which at least 2 out of 6 patients experience DLT.

recommended phase II dose of LNA-i-miR-221 (RP2D) using escalating doses for further evaluation

Peak Plasma Concentration of LNA-i-miR-221

plasma concentration-time profile of LNA-i-miR-221

the total body clearance of LNA-i-miR-221

Preliminary assessment of the clinical benefit and antitumoral activity of LNA-i-miR-221 based on RECIST V1.1 criteria

Associazione Italiana per la Ricerca sul Cancro

Azienda Ospedaliera Universitaria Mater Domini, Catanzaro

Professor of Medical Oncology, Magna Graecia University, Catanzaro, Italy

Symptoms and General Pathology

Neoplasm Metastasis

Neoplastic Processes

VNP20009

This study will examine the safety and toxicities of intravenously administering a genetically modified type of Salmonella bacteria (VNP20009) and its impact on tumor growth in advanced or metastatic cancer (cancer that has spread from the primary site). The first patients in the study will be given the smallest dose of VNP20009, and those who enter later will receive increasingly larger doses. This will be done to determine the maximum dose that can be given without serious side effects.

Normally, Salmonella bacteria ingested in food or water can cause diarrhea or more severe illness. The bacteria in this study are altered genetically so they can be injected through a vein and circulate in the blood with less likelihood of causing side effects. It is believed that the bacteria will travel in the blood to the tumor and infect it. In studies of mice, tumor growth slowed in animals whose tumors were infected with VNP0009.

Patients with advanced or metastatic cancer 18 years of age or older whose disease is not responding to standard treatment, or for which there is no treatment, may be eligible for this study. Candidates will undergo a medical history and physical examination, including blood tests, scans, X-rays, electrocardiogram, and urine, stool and blood cultures.

Study participants will be admitted to the hospital for 2 to 4 days. On day 1, they will receive the first dose of VNP0009, infused over a 30-minute period through an intravenous catheter (a small plastic tube inserted into a vein). Blood will be drawn every day to determine if the bacteria are still in the body. After discharge, patients will return to the hospital on days after approximately 1-2 weeks and again after 4-5 weeks for additional blood tests to measure levels of the bacteria and for collection of blood, urine and stool samples. Patients whose tumors are on or just beneath the skin may be asked to have one or two tumors removed surgically.

Patients will have tests after approximately 4-5 weeks, including CTs and X-rays, to determine the size and extent of the tumor. Patients whose tumor remained the same size or smaller than before starting treatment, and whose side effects were acceptable will be offered a second treatment cycle. Those whose tumor grew during treatment will be taken off the study. Patients remaining in the study will begin the second cycle on approximately day 36. Tumor growth will be evaluated again between days 64 and 70, and a third cycle will be offered to patients whose tumors have remained stable or have shrunk. Patients may have up to 12 treatment cycles as long as evaluations continue to show the tumor is stable or shrinking. Completing all 12 cycles takes about 13 months. Patients will continue to be evaluated after treatment ends, if they agree to continued follow-up.

Patients must follow health precautions to prevent infecting others with Salmonella bacteria as long as they, themselves, remain infected. These include, for example, stringent hand washing practices and avoiding contact with people with weakened immune systems. All the precautions will be explained to the study participants.

Patients who leave the study must take antibiotic therapy to rid the body of any remaining bacteria. They will return for urine, stool and blood cultures 30 days after the start of antibiotics, and may undergo three types of scans to look for sites of infection. Treatment will be given as needed.

Patients with metastatic cancer will receive the intravenous injection of live genetically modified Salmonella typhimurium. This bacteria has been genetically modified to alter its pathogenicity and to attempt to increase its localization to sites of growing cancer. Cohorts of patients will receive increasing doses of the bacteria to establish the maximum tolerated dose.

Treatment of Patients With Cancer With Genetically Modified Salmonella Typhimurium Bacteria

A Phase I Trial of a Live, Genetically Modified Salmonella Typhimurium (VNP20009) for the Treatment of Cancer by Intravenous Administration

National Cancer Institute (NCI)

ABBV-399 via intravenous administration at escalating dose levels.

ABBV-399

An open-label, dose-escalation study designed to evaluate the safety, pharmacokinetics, and preliminary efficacy of ABBV-399 in participants with advanced solid tumors.

A Study to Evaluate the Safety and Pharmacokinetics ABBV-399 in Japanese Participants With Solid Tumors

A Phase I Study to Evaluate the Safety and Pharmacokinetics of ABBV-399 in Japanese Subjects With Advanced Solid Tumors

AUC (0-t) is defined as area under the concentration versus time curve from time zero (pre-dose) to the time of the last measurable concentration.

MTD/MAD is defined as the highest dose level at which less than 2 of 6 (or \< 33% if cohort is expanded beyond 6) participants experience a dose limiting toxicity.

PFS time is defined as the time from the participant's first dose of ABBV-399 to either the participant's disease progression or death, whichever occurs first.

Objective response rate (ORR) is defined as the proportion of participants with a confirmed partial or complete response to the treatment. Evaluation of tumor response is based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

DOR is defined as the time from the participant's initial objective response to study drug therapy to disease progression or death, whichever occurs first.

Recurrence

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Interleukin-12

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Cohorts of 3-6 pts will be infused with escalating doses of modified T cells to establish the MTD of modified T cells. There are 5 planned dose levels: 3 x 10\^5, 1 x 10\^6, 3 x 10\^6, \& 1 x 10\^7 \& 3 x 10\^7 4H11-28z/fIL-12/EGFRt+ T cells/kg. Cohort I-IV \& VI will be treated escalating dose levels. Once the MTD of T cells is established, the next cohort will receive lymphodepleting cyclophosphamide dose of 750 mg/m\^2 or a regimen of cyclophosphamide dose 300 mg/m2 x 3 days concurrent with fludarabine dose 25-30 mg/m2 x 3 days 2-7 days prior to starting the T cell infusion at one dose level below the MTD. If MTD isn't established after Cohort IV, Cohort V will receive conditioning chemotherapy 2-7 days prior to starting the T cell infusion at the same dose as Cohort III. Pts in Cohort V received cyclophosphamide chemotherapy on Day 1 or cyclophosphamide concurrent with fludarabine on Day 1-3, followed 2 to 4 days later by T cell infusion. This cohort is closed to further accrual.

Production of Genetically-modified T cells

IP Catheter Insertion

Patients who do not have sufficient CAR T cells for the assigned dose cohort will be treated in the cohort for which cells are available.

Infusion of 4H11-28z/fIL-12/EGFRt+ Genetically-modified T cells

Roisin O'Cearbhaill, MD

The purpose of this phase I study is to test the safety of different dose levels of specially prepared cells collected called "modified T cells". In the screening part of this study the tumor was found to have a protein called MUC16. This protein is present on about 70% of ovarian cancers. The investigators want to find a safe dose of modified T cells for patients with this type of cancer that has progressed after standard chemotherapy. We also want to find out what effects these modified T cells have on the patient and their cancer.

There are 2 phases to the study: the Screening Phase and the Intervention Phase. Only patients identified as eligible from the Screening Phase may enroll in the Intervention Phase.

Screening Phase: After signing Informed Consent 1 (Screening Informed Consent), the patient's MUC16ecto tumor expression will be determined as previously described. In order to be eligible for this protocol, the patient's ovarian, primary peritoneal or fallopian tube carcinoma must express the MUC16ecto protein detectable by IHC analysis of banked (paraffin embedded) or fresh biopsied tumor. After signing Informed Consent 1, approximately 2 weeks will elapse while the patient's banked tumor is tested for MUC16ecto expression. If a patient's tumor is found to express MUC16ecto, she will undergo leukapheresis for the collection of peripheral blood mononuclear cells (PBMC), which will be frozen for future use. The leukapheresis product will be stored until the end of the study in case future research tests related to this study are developed.

Intervention Phase: Patients must sign Informed Consent 2 (Intervention Informed Consent) before receiving treatment on the study before receiving treatment on the study.

Once the patient is eligible to receive the CAR+ T cells, the frozen leukapheresis product will be thawed and used to generate the 4H11-28z/fIL-12/EGFRt+ genetically-modified T cells. It is expected to take approximately 4-6 weeks to prepare the autologous CAR+ T cells.

On day 1-3 patients in cohorts V will receive conditioning chemotherapy with cyclophosphamide 750 mg/m\^2 or 300 mg/m2 cyclophosphamide concurrent with 25-30 mg/m2 fludarabine 2-7 days prior to the initial infusion of autologous CAR+T cells. Patients will receive autologous CAR+T cells in 2 infusions, the first IV and the second IP, each comprising about half the total dose. The IV infusion will be given first. The patient will then be closely monitored. One to 3 days later if clinically stable, the patient will receive the remaining dose of CAR+T cells IP. Patients in cohort I or -I will not receive cyclophosphamide, but will receive the T cells in the same manner (approximately half IV, followed by close monitoring and then 1-3 days later, if the patient is clinically stable, the remaining cells will be administered IP).

This is a standard phase I dose escalation trial.

Cyclophosphamide Followed by Intravenous and Intraperitoneal Infusion of Autologous T Cells Genetically Engineered to Secrete IL-12 and to Target the MUC16ecto Antigen in Patients With Recurrent MUC16ecto+ Solid Tumors

A Phase I Clinical Trial of Cyclophosphamide Followed by Intravenous and Intraperitoneal Infusion of Autologous T Cells Genetically Engineered to Secrete IL-12 and to Target the MUC16ecto Antigen in Patients With Recurrent MUC16ecto+ Solid Tumors

There are 5 planned dose levels of 4H11-28z/fIL-12/EGFRt+ T cells: 3 x 10\^5, 1 x 10\^6, 3 x 10\^6, and 1 x10\^7 and 3 x10\^7 4H11-28z/fIL-12/EGFRt+ T cells/kg. The first subject will be treated at dose level 1 (3 x 10\^5 4H11-28z/fIL-12/EGFRt+ T cells/kg). At least one week will elapse from the first patient's T cell infusions before the second patient is treated (on dose level 1) to allow for toxicity and safely assessment. 3 subjects will be enrolled in cohort I and followed for 30 days for safety assessments. If no DLT is observed after all three subjects have been observed for 30 days, a second cohort of 3 subjects will be enrolled at the same dose level (3 x 10\^54H11-28z/fIL-12/EGFRt+ T cells/kg) with the addition of cyclophosphamide plus or minus fludarabine.

which will be defined according to the RECIST criteria, version 1.1 and, in appropriate subjects, the immune-related Response Criteria (irRC) (80)

Stanford University

Juno Therapeutics, Inc., a Bristol-Myers Squibb Company

Memorial Sloan Kettering Cancer Center

Leukemia

Leukemia, Myeloid

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Philadelphia Chromosome

Lymphoma

Lymphatic Diseases

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Translocation, Genetic

Chromosome Aberrations

Myeloid Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

Acute Graft Versus Host Disease

Lymphosarcoma

Chronic Myeloproliferative Disorders

Amino Acids

Asciminib

Nilotinib

Dasatinib

Imatinib Mesylate

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Dose escalation study estimated the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of asciminib in adult patients with chronic myeloid leukemia (CML).

Dose escalation study estimated the MTD and/or RDE of asciminib in combination with Nilotinib in adult CML patients

Dose escalation study estimated the MTD and/or RDE of asciminib in adult patients with Ph positive ALL patients

Dose escalation study to estimate the MTD and/or RDE of asciminib in combination with imatinib in adult CML patients

Dose escalation study estimated the MTD and/or RDE of asciminib in combination with dasatinib in adult CML patients

Asciminib was be administered orally in a dose escalation schedule.

Asciminib (ABL001)

Asciminib and Nilotinib was administered orally in CML patients

Asciminib and imatinib was administered orally in CML patients

Imatinib

Asciminib and dasatinib was administered orally in CML patients

Novartis Pharmaceuticals

The design of a phase I, open label, dose finding study was chosen in order to establish a safe and tolerated dose of single agent ABL001 in Chronic myeloid leukemia (CML) and Philadelphia chromosome positive Acute lymphoblastic leukemia (Ph+ ALL) patients who are relapsed or refractory to or are intolerant of Tyrosine kinase inhibitors (TKIs), and of ABL001+Nilotinib, ABL001+Imatinib and ABL001+Dasatinib in Ph positive CML patients who are relapsed or refractory to TKIs.

This first-in-human trial with ABL001 was a dose escalation study whose primary purpose was to estimate the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of single agent ABL001 in CML or Ph+ ALL patients, and in combination with either Nilotinib or Imatinib or Dasatinib in Ph positive CML patients. The safety, tolerability and pharmacokinetic (PK) profile of ABL001 and ABL001+Nilotinib, ABL001+Imatinib and ABL001+Dasatinib were assessed together with an evaluation of pharmacodynamic (PD) changes in peripheral blood mononuclear cells (PBMC) and bone marrow aspirates and all data could contribute to the assessment of the RDE.

An understanding of the MTD/RDE, safety profile, PK/PD relationship, and preliminary evidence of anti-CML and ALL activity wias used to inform future development in adults with CML and Ph+ ALL. By virtue of its distinct pharmacological profile and by preclinical pharmacological studies demonstrating an additive effect, a combination of ABL001 and a tyrosine-kinase inhibitor (TKI) has the potential to achieve a deeper molecular response in a higher proportion of CML patients as compared to single agent TKI therapy. Such a combination has the added advantage of targeting the ABL kinase domain at two distinct locations, theoretically preventing single point mutation-associated treatment resistance. The prediction is that a nilotinib+ABL001, imatinib+ABL001 and/or dasatinib+ABL001 combination will increase the percentage of patients who achieve a complete molecular response (CMR) and decrease the time to CMR, thereby increasing the possibility of achieving sustained treatment-free remissions in these patients. In addition, some patients could be intolerant of therapy with TKIs or could develop mutations that promote resistance to TKI therapy. In these patients, ABL001 could provide a novel therapeutic option.

A Phase I Study of Oral Asciminib (ABL001) in Patients With CML or Ph+ ALL

A Phase I, Multicenter, Open-label Study of Oral ABL001 in Patients With Chronic Myelogenous Leukemia (CML) or Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia (Ph+ ALL)

Determine the MTD and/or RDE of ABL001 as single agent in CML and Ph+ ALL, and in combination with either nilotinib or imatinib or dasatinib in CML patients

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
SC-004 Alone or With ABBV-181 in Subjects With Epithelial Ovarian, Fallopian Tube, Primary Peritoneal and Endometrial Cancers	NCT03138408	Cancer	SC-004 ABBV-181	18 Years -	AbbVie
A Study of SC-007 in Subjects With Advanced Cancer	NCT03253185	Colorectal Canc... Gastric Cancer	SC-007	18 Years -	AbbVie
A Dose Escalation Study of LNA-i-Mir-221 for Cancer Treatment	NCT04811898	Multiple Myelom... Hepatocarcinoma Advanced Solid ...	LNA-i-miR-221	18 Years -	Azienda Ospedaliera Universitaria Mater Domini, Catanzaro
Treatment of Patients With Cancer With Genetically Modified Salmonella Typhimurium Bacteria	NCT00004988	Cancer Neoplasm Neoplasm Metast...	VNP20009	-	National Institutes of Health Clinical Center (CC)
SC-004 Alone or With ABBV-181 in Subjects With Epithelial Ovarian, Fallopian Tube, Primary Peritoneal and Endometrial Cancers	NCT03138408	Cancer	SC-004 ABBV-181	18 Years -	AbbVie
A Study to Evaluate the Safety and Pharmacokinetics ABBV-399 in Japanese Participants With Solid Tumors	NCT03311477	Advanced Solid ...	ABBV-399	20 Years -	AbbVie
Cyclophosphamide Followed by Intravenous and Intraperitoneal Infusion of Autologous T Cells Genetically Engineered to Secrete IL-12 and to Target the MUC16ecto Antigen in Patients With Recurrent MUC16ecto+ Solid Tumors	NCT02498912	Solid Tumors	Production of G... Cyclophosphamid... IP Catheter Ins... Infusion of 4H1... Fludarabine	18 Years -	Memorial Sloan Kettering Cancer Center
A Phase I Study of Oral Asciminib (ABL001) in Patients With CML or Ph+ ALL	NCT02081378	Chronic Myeloge... Philadelphia Ch...	Asciminib (ABL0... Nilotinib Imatinib Dasatinib	18 Years -	Novartis
A Study of SC-005 in Subjects With Triple Negative Breast Cancer (TNBC)	NCT03316794	Breast Cancer	SC-005	18 Years -	AbbVie

Spots Global Cancer Trial Database for maximum tolerated dose (mtd)