Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Camurati-Engelmann Disease

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Oxaliplatin

Bevacizumab

Leucovorin

Fluorouracil

Irinotecan

Antibodies

Antibodies, Monoclonal

Tislelizumab

Levoleucovorin

Immunoglobulins

Mitogens

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antidotes

Protective Agents

Folic Acid

Vitamin B Complex

Trace Elements

Folinic Acid

Folate

Vitamin B9

In the safety run-in part for investigational arm 1, participants will be treated with a combination of SOC anti-cancer therapy (bevacizumab with either modified FOLFOX6 or FOLFIRI) and NIS793 to confirm the RP2D of the NIS793

In the expansion part, participants in the investigational arm 1 will be treated with a combination of SOC anti-cancer therapy (bevacizumab with either modified FOLFOX6 or FOLFIRI) and NIS793 at the RP2D defined in the safety run-in

In the expansion part, participants in the control arm will be treated with a combination of SOC anti-cancer therapy (bevacizumab with either modified FOLFOX6 or FOLFIRI)

In the safety run-in part for investigational arm 2, participants will be treated with a combination of SOC anti-cancer therapy (bevacizumab with either modified FOLFOX6 or FOLFIRI), NIS793 and tislelizumab to confirm the RP2D of NIS793.

In the expansion part, participants in the investigational arm 2 will be treated with a combination of SOC anti-cancer therapy (bevacizumab with either modified FLOFOX6 or FOLFIRI) with NIS793 and tislelizumab at the RP2D for NIS793 defined in the safety run-in

Investigational drug NIS793 will be administered intravenously (IV) at the dose and schedule determined in the safety run-in part.

NIS793

5-fluorouracil \[continuous infusion\], leucovorin \[administered IV\] (or levoleucovorin \[administered IV\]), and oxaliplatin \[administered IV\]

Modified FOLFOX6

5-fluorouracil \[continuous infusion\], leucovorin \[administered IV\] (or levoleucovorin \[administered IV\]), and irinotecan \[administered IV\]

FOLFIRI

Investigational drug tislelizumab will be administered intravenously (IV).

Novartis Pharmaceuticals

The purpose of this study is to evaluate the preliminary efficacy and safety of NIS793 and other novel investigational combinations with standard of care (SOC) anti-cancer therapy vs SOC anti-cancer therapy for the second line treatment of mCRC.

This study aims to explore whether different mechanisms of action may reverse resistance and improve responsiveness to the currently considered SOC anti-cancer therapy in the second line metastatic colorectal cancer (mCRC) setting.

This is an open-label, multi-center, phase II, 2-part platform study with Safety run-in and Expansion parts.

The platform design of this study is adaptive to allow flexibility in the introduction of additional treatment arms with new investigational drugs in combination with SOC anti-cancer therapy for the second line treatment of mCRC.

The study will include a control arm that will enroll participants treated with SOC anti-cancer therapy (bevacizumab with mFOLFOX6 or FOLFIRI) for the second line treatment of mCRC. The choice of the chemotherapy medications (mFOLFOX6 or FOLFIRI) will be determined by the Investigator based on prior exposure to oxaliplatin or irinotecan.

Each investigational arm will include a combination of an investigational drug and the SOC anti-cancer therapy. The first investigational arm of the study will explore the combination of anti-transforming growth factor β (TGF-β) monoclonal antibody, NIS793 with SOC anti-cancer therapy. The second investigational arm of the study will explore the combination of anti-transforming growth factor β (TGF-β) monoclonal antibody, NIS793 with Tislelizumab, which is an anti-PD1 monoclonal antibody, and SOC anti-cancer therapy. Combination of other investigational drugs with SOC anti-cancer therapy may be added by protocol amendments an additional investigational arms.

In each investigational arm, a Safety run-in part will be conducted before opening the expansion part to confirm the recommended phase 2 dose (RP2D) for a combination of any investigational drug with SOC anti-cancer therapy unless the dose has been confirmed externally to this trial.

The decision to open the Expansion part of the study will be based on dose confirmation of investigational drug with available safety, relevant PK and other relevant data from Safety run-in part. Participants in the expansion part will be randomized in 1:2 ratio to the control arm or investigational arm.

Study of NIS793 and Other Novel Investigational Combinations With SOC Anti-cancer Therapy for the 2L Treatment of mCRC

An Open-label, Multi-center, ph II Platform Study Evaluating the Efficacy and Safety of NIS793 and Other New Investigational Drug Combinations With SOC Anti-cancer Therapy for the 2L Treatment of Metastatic Colorectal Cancer (mCRC)

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Percentage of participants with DLTs during the first cycle of treatment. A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness or concomitant medication that occurs within the first cycle of treatment with NIS793 with or without tislelizumab in combination with Bevacizumab and modified FOLFOX6/ FOLFIRI and meets protocol defined DLT criteria.

PFS defined as the time from the date of enrollment (run-in part) or randomization (randomized part) to the date of the first documented progression based on investigator assessment and according to RECIST 1.1 or death due to any cause.

Percentage of participants with AEs and SAEs including changes in laboratory parameters, vital signs, body weight and cardiac assessments

Tolerability measured by the percentage of subjects who have dose adjustments (interruptions or reductions) of investigational drug (e.g. NIS793, NIS793+tislelizumab)

Tolerability measured by the dose intensity of investigational drug (e.g. NIS793, NIS793+tislelizumab). Dose intensity will be computed as the ratio of actual cumulative dose received and actual duration of exposure

PFS defined as the time from the date of enrollment to the date of the first documented progression based on investigator assessment and according to RECIST 1.1 or death due to any cause.

ORR is defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR), as per investigator assessment and according to RECIST 1.1

DCR is the proportion of participants with BOR of CR or PR or stable disease (SD) as per investigator assessment and according to RECIST 1.1

DOR is defined as the duration of time between the date of the first documented response (CR or PR) and the date of first documented progression or death due to any cause

OS is defined as the time from the date of enrollment to date of death due to any cause.

TTR is defined as the duration of time between the date of enrollment and the date of first documented response of either CR or PR.

Tolerability measured by the percentage of subjects who have dose adjustments (interruptions) of investigational drug (e.g. NIS793, NIS793+tislelizumab)

Tolerability measured by the dose intensity of investigational drug (e.g. NIS793, NIS793+Tislelizumab). Dose intensity will be computed as the ratio of actual cumulative dose received and actual duration of exposure

Blood samples will be collected at indicated time-points for analysis of Cmax of NIS793

Blood samples will be collected at indicated time-points for analysis of Cmax of tislelizumab

Blood samples will be collected at indicated time-points for analysis of Ctrough of NIS793

Blood samples will be collected at indicated time-points for analysis of Ctrough of tislelizumab

Prevalence of ADA (anti-NIS793, anti-tislelizumab) at baseline is defined as the proportion of participants who have an ADA positive result at baseline

Incidence of ADA (anti-NIS793, anti-tislelizumab) on treatment is defined as the proportion of participants who are treatment-induced ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer)

Symptoms and General Pathology

Blood and Lymph Conditions

Syndrome

Preleukemia

Myelodysplastic Syndromes

Bone Marrow Diseases

Hematologic Diseases

Precancerous Conditions

Treatment with MBG453 single agent Q4W to confirm safety and tolerability of RD.

Treatment with NIS793 single agent Q3W to establish RD in this indication and confirm safety and tolerability.

Treatment with single agent canakinumab Q4W to confirm safety and tolerability of RD.

Treatment with combination of MBG453 and NIS793 Q3W to confirm safety and tolerability of combination RD.

Treatment with MBG453 + canakinumab combination Q4W to confirm safety and tolerability of combination RD.

MBG453

canakinumab

The purpose of this study was to characterize the safety, tolerability and confirm the dose for select single agents and combinations in patients with lower risk (very low, low, and intermediate risk) MDS.

This was a phase Ib, multi center, open-label, platform study with multiple treatment arms.

The design of this study was adaptive to allow discontinuation of poorly tolerated or ineffective treatments and to facilitate the introduction of new candidate single agents or combinations. Study design included a dose escalation/confirmation part and a dose expansion.

The planned initial single agent and combination treatment arms were the following:

* Arm 1: MBG453 single agent
* Arm 2: NIS793 single agent
* Arm 3: canakinumab single agent
* Arm 4: MBG453 + NIS793 combination
* Arm 5: MBG453 + canakinumab combination Patients were treated in the dose confirmation/escalation part of the study in Arms 1, 2, 3 and 5. No patients were treated in Arm 4. The study did not progress into the expansion phase.

Phase Ib Study of Select Drug Combinations in Patients With Lower Risk MDS

A Phase Ib, Multicenter, Open-label Platform Study of Select Drug Combinations in Adult Patients With Lower Risk (Very Low, Low, or Intermediate Risk) Myelodysplastic Syndrome

Incidence of dose limiting toxicities (DLTs) during the first 2 cycle of treatment during the dose escalation/confirmation part

Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) as per CTCAE v5.0, by treatment

The number of red cell or platelet transfusions a patient receives over the course of study treatment will be compared to the patient's baseline transfusion requirements based on the number of transfusions received during the 16-weeks period prior to the start of study treatment.

Red cell or platelet transfusion independence is defined as no red cell or platelet transfusions with a duration lasting for 8, 12, 16, or 24 weeks.

Hemoglobin levels over the course of the study will be compared to the patient's baseline level to monitor for improvements in anemia.

Platelet count over the course of the study will be compared to the patient's baseline count to monitor for improvements in thrombocytopenia.

BOR is the best disease response recorded from the start of the treatment until disease progression/relapse. The subject's BOR will be calculated based on investigator's response evaluations per International Working Group (IWG) criteria.

Time to onset of either red cell transfusion independence or platelet transfusion independence.

Time to onset of BOR is defined as the time between date of start of study treatment to the date of first onset of Partial Response (PR) or better response.

DOR is defined as the duration from the first documented onset of complete response (CR), complete remission with partial hematologic recovery (CRh), bone marrow CR (mCR) or PR to the date of disease progression (PD) or relapse or death due to myelodysplastic syndrome (MDS).

ORR is the proportion of subjects with a best overall response of either CR or CRh, or mCR or PR.

PFS is defined as the time from the start of treatment until death due to any reason, disease progression, or relapse, whichever comes first.

TTP is the time from the start of treatment to the date of PD, relapse or death due to underlying cancer.

Serum concentrations and derived PK parameters

Anti-drug antibody prevalence at baseline and on treatment.

Gland and Hormone Related Diseases

Adenocarcinoma

Pancreatic Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Endocrine Gland Neoplasms

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Bone Density Conservation Agents

Capecitabine

Calcium

Camptothecin

Folfirinox

Calcium, Dietary

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Participants will be randomly assigned to receive:

* FOLFIRINOX + NIS793 on day 1 of each 14 day cycle up to 8 cycles/16 weeks
* Cycles 9+: Based on study team determination, some participants may be offered chemoradiation following completion of chemotherapy and/or surgery following either completion of chemotherapy or chemoradiation

Participants will be randomly assigned to receive:

* FOLFIRINOX on day 1 of each 14 day cycle up to 8 cycles/16 weeks
* Cycles 9+: Based on study team determination, some participants may be offered chemoradiation following completion of chemotherapy and/or surgery following either completion of chemotherapy or chemoradiation

Combination of the drugs 5-Fluorouracil (5-FU), Oxaliplatin, Irinotecan, and Leucovorin given by intravenous infusion

mFOLFIRINOX

Part of the FOLFIRINOX drug combination, given by intravenous infusion

5-Fluorouracil (5-FU)

Combination of Chemo (Capecitabine) and Radiation Therapy

Chemoradiation

Surgery

Kimberly Perez, MD

This study is being done to evaluate the safety and efficacy of adding NIS793 to standard of care FOLFIRINOX treatment for pancreatic cancer.

The names of the study interventions involved in this study are:

* NIS793
* FOLFIRINOX (Folinic acid/Leucovorin, 5-Fluorouracil, Irinotecan, and Oxaliplatin)

Other interventions may include:

* Chemoradiation Therapy
* Surgery

This is a randomized phase 2 study evaluating the efficacy of NIS793, a TGF-beta inhibitor, when added to a standard chemotherapy program of modified FOLFIRINOX for people with previously-untreated, resectable or borderline resectable pancreatic adenocarcinoma.

The U.S. Food and Drug Administration (FDA) has not approved NIS793 as a treatment for any disease. NIS793 works by blocking a molecule called TGF-beta. TGFbeta has been shown to promote the growth of pancreatic cancer and this study is examining if the addition of a TGF-beta blocking drug will allow the chemotherapy to work better against the cancer.

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.

Participants will be randomized into two groups of:

* Arm A will receive standard chemotherapy, mFOLFIRINOX, in combination with NIS793.
* Arm B will receive standard chemotherapy, mFOLFIRINOX.

Based on study team determination, some participants may be offered chemoradiation following completion of chemotherapy and/or surgery following either completion of chemotherapy or chemoradiation.

Study treatment is expected to last up to 16 weeks unless disease symptom worsens .

It is expected that about 45 people will take part in this research study.

A Trial of NIS793 With FOLFIRINOX in Pancreatic Cancer

A Phase 2 Study of Neoadjuvant NIS793 in Combination With mFOLFIRINOX in Resectable and Borderline Resectable Pancreatic Adenocarcinoma (PDAC)

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Major pathological response (MPR) defined as \<5% residual tumor cells visible in the pancreatic resection specimen. The major pathological response rate will be analyzed among all patients who start protocol therapy, including those not resected due to early progression, death or off study.

All grade 3 or higher adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv5 as reported on case report forms will be counted. Rate is the proportion of treated participants experiencing at least one treatment-related grade 3 or higher AE of any type during the time of observation.

Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. Per RECIST 1.1 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.

OS is based on the Kaplan-Meier method, defined as the time from study entry to death or censored at date last known alive.

Novartis

Principal Investigator

Skin and Connective Tissue Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Breast Neoplasms

Lung Neoplasms

Carcinoma, Hepatocellular

Carcinoma, Renal Cell

Liver Neoplasms

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Liver Diseases

Renal Cell Carcinoma

Spartalizumab

Immune Checkpoint Inhibitors

Anti-TGF beta antibody tested on a Q3W regimen or alternative Q2W regimen.

Anti-PD-1 antibody tested on a Q3W regimen or alternative Q4W regimen.

PDR001

To characterize the safety and tolerability of NIS793 as single agent and in combination with PDR001 and to identify recommended doses for future studies.

Phase I/Ib Study of NIS793 in Combination With PDR001 in Patients With Advanced Malignancies.

A Phase I/Ib, Open-label, Multi-center Dose Escalation Study of NIS793 in Combination With PDR001 in Adult Patients With Advanced Malignancies

Evaluate the anti-tumor activity per RECIST as well as per immune related Response Criteria (irRC) of NIS793 as single agent and in combination with PDR001 every 2 cycles from start of treatment until cycle 9 then every 3 cycles until end of treatment (if applicable).

Evaluate the anti-tumor activity per RECIST as well as per immune related Response Criteria (irRC) of NIS793 as single agent and in combination with PDR001every 2 cycles from start of treatment until cycle 9 then every 3 cycles until end of treatment (if applicable).

Evaluate the anti-tumor activity per RECIST as well as per immune related Response Criteria (irRC) of NIS793 as single agent and in combination with PDR001 every2 cycles from start of treatment until cycle 9 then every 3 cycles until end of treatment (if applicable).

Evaluate the anti-tumor activity per RECIST as well as per immune related Response Criteria (irRC) of NIS793 as single agent and in combination with PDR001 every 2 cycles from start of treatment until cycle 9 then every 3 cycles until end of treatment. During disease progression f/u, every 8 weeks for 40 weeks, then every 12 weeks.

Evaluate serum concentration of NIS793 and PDR001 up to 8 cycles after start of treatment and at end of treatment.

Assess the emergence of anti-NIS793 and anti-PDR001 antibodies up to 8 cycles after start of treatment and at end of treatment.

Assess the concentration of anti-NIS793 and anti-PDR001 antibodies up to 8 cycles after start of treatment and at end of treatment.

Characterize the pharmacokinetic properties of NIS793 given alone and in combination with PDR001.

Assess change from baseline of immune infiltrates in tumor biopsies after 2 cycles of treatment.

Assess change from baseline in immunological markers in tumor biopsies after 2 cycles of treatment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of NIS793 and Other Novel Investigational Combinations With SOC Anti-cancer Therapy for the 2L Treatment of mCRC	NCT04952753	Metastatic Colo...	NIS793 Bevacizumab Modified FOLFOX... FOLFIRI Tislelizumab	18 Years -	Novartis
Phase Ib Study of Select Drug Combinations in Patients With Lower Risk MDS	NCT04810611	Myelodysplastic...	MBG453 NIS793 canakinumab	18 Years -	Novartis
A Trial of NIS793 With FOLFIRINOX in Pancreatic Cancer	NCT05546411	Pancreatic Canc... Resectable Panc... Borderline Rese... Pancreatic Aden...	mFOLFIRINOX 5-Fluorouracil ... Oxaliplatin Irinotecan Leucovorin NIS793 Chemoradiation Surgery	18 Years -	Dana-Farber Cancer Institute
Phase I/Ib Study of NIS793 in Combination With PDR001 in Patients With Advanced Malignancies.	NCT02947165	Breast Cancer Lung Cancer Hepatocellular ... Colorectal Canc... Pancreatic Canc... Renal Cancer	NIS793 PDR001	18 Years -	Novartis
Study of Select Combinations in Adults With Myelofibrosis	NCT04283526	Primary Myelofi... Myelofibrosis PMF Post-Essential ... Post-Polycythem...	MBG453 NIS793 Spartalizumab Decitabine	18 Years -	Novartis
Phase I/Ib Study of NIS793 in Combination With PDR001 in Patients With Advanced Malignancies.	NCT02947165	Breast Cancer Lung Cancer Hepatocellular ... Colorectal Canc... Pancreatic Canc... Renal Cancer	NIS793 PDR001	18 Years -	Novartis
A Trial of NIS793 With FOLFIRINOX in Pancreatic Cancer	NCT05546411	Pancreatic Canc... Resectable Panc... Borderline Rese... Pancreatic Aden...	mFOLFIRINOX 5-Fluorouracil ... Oxaliplatin Irinotecan Leucovorin NIS793 Chemoradiation Surgery	18 Years -	Dana-Farber Cancer Institute
Study of Efficacy and Safety of NIS793 in Combination With Standard of Care (SOC) Chemotherapy in First-line Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC) - daNIS-2	NCT04935359	Metastatic Panc...	NIS793 Nab-paclitaxel Gemcitabine Placebo	18 Years -	Novartis

Spots Global Cancer Trial Database for nis793

Every month we try and update this database with for nis793 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for nis793

Every month we try and update this database with for nis793 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for nis793 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.