Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare 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

Antineoplastic Agents

All Drugs and Chemicals

Lenalidomide

Bortezomib

Daratumumab

Pomalidomide

Nirogacestat

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Gamma Secretase Inhibitors and Modulators

Enzyme Inhibitors

Participants will receive teclistamab plus daratumumab plus pomalidomide.

Participants will receive teclistamab plus daratumumab plus lenalidomide plus bortezomib in 21-day cycles.

Participants will receive teclistamab plus nirogacestat.

Participants will receive teclistamab plus lenalidomide.

Participants will receive teclistamab plus daratumumab plus lenalidomide.

Participants will receive teclistamab plus daratumumab plus lenalidomide plus bortezomib in 28-day cycles.

Teclistamab

Janssen Research and Development, LLC Clinical Trial

The purpose of this study is to characterize the safety and tolerability of teclistamab when administered in different combination regimen and to identify the optimal dose(s) of teclistamab combination regimens.

A Study of Teclistamab With Other Anticancer Therapies in Participants With Multiple Myeloma

A Multi-arm Phase 1b Study of Teclistamab With Other Anticancer Therapies in Participants With Multiple Myeloma

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

An AE can be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product.

Number of participants with AEs by severity will be reported.

Number of participants with abnormalities in laboratory values (such as serum chemistry, hematology) will be reported.

The Dose Limiting Toxicities (DLTs) are based on drug related adverse events and defined as any of the following events: hematological / non hematological toxicity of Grade 3 or higher.

ORR is defined as the proportion of participants who achieve partial response (PR) or better according to the international myeloma working group (IMWG) 2016 criteria.

VGPR or better response rate is defined as the proportion of participants who achieve a VGPR or better response (stringent complete response \[sCR\]+ complete response \[CR\]+VGPR) according to the IMWG 2016 criteria.

CR or better response rate is defined as the proportion of participants who achieve a CR or better response (sCR+CR) according to the IMWG 2016 criteria.

sCR rate is defined as the proportion of participants who achieve an sCR according to the IMWG 2016 criteria.

Duration of response is defined as time from date of initial documentation of a response (PR or better) to date of first documented evidence of progressive disease (PD), per IMWG criteria.

Time to response is defined as the time between date of first dose of study treatment and the first efficacy evaluation at which the participant has met all criteria for PR or better.

Serum concentrations of teclistamab will be reported.

Serum concentrations of daratumumab will be reported.

Serum concentration of nirogacestat will be reported.

Number of participants with anti-drug antibodies to teclistamab will be reported for all treatment regimens.

Number of participants with anti-drug antibodies to daratumumab will be reported for Treatment Regimen A, B, E and F.

Number of participants with anti-drug antibodies to rHuPH20 will be reported for Treatment Regimen A, B, E and F.

Janssen Research & Development, LLC

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Recurrence

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Granulosa Cell Tumor

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Sex Cord-Gonadal Stromal Tumors

Ovarian Cancer

Ovarian Epithelial Cancer

Granulosa Cell Tumor of the Ovary

All participants will receive open-label nirogacestat

This phase 2 clinical trial will study the effectiveness of nirogacestat in ovarian granulosa cell tumors (OvGCTs). Nirogacestat is a gamma secretase inhibitor (GSI) which is hypothesized to decrease the growth and activity of ovarian granulosa tumors.

Ovarian granulosa cell tumors (OvGCTs) represent 5-7% of all ovarian cancers (\~1.5 to 2k newly diagnosed patients/year in the United States) and are the most common subtype of ovarian sex cord tumors (70%). Treatment of granulosa cell tumors with nirogacestat is expected to inhibit Notch-induced granulosa cell proliferation.

This is a multi-center, single-arm, Phase 2 open label treatment study to determine the efficacy, safety, tolerability, and pharmacokinetics of nirogacestat in adult participants with relapsed/refractory OvGCT. The participants will continue treatment until disease progression as determined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (unless the participants meet criteria for continued treatment) or unacceptable toxicity.

Nirogacestat in Ovarian Granulosa Cell Tumors

A Phase 2 Trial of Nirogacestat in Patients With Recurrent Ovarian Granulosa Cell Tumors

SpringWorks Therapeutics is committed to data transparency and sharing data to further research while maintaining the privacy and confidentiality of research participants. Pertinent patient-level data from completed clinical trials will be made available by SpringWorks to qualified researchers upon approval of reasonable requests following de-identification/anonymization pursuant to applicable law.

The proportion of participants with complete response (CR) + partial response (PR) assessed using RECIST v1.1 criteria.

The number of participants without progression according to RECIST v1.1 or death at 6 months.

The number of participants who have not died of any cause.

Change from baseline as measured by Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI).

The time from response (CR + PR using RECIST v.1.) to disease progression and/or death

SpringWorks Therapeutics, Inc.

Behaviors and Mental Disorders

Skin and Connective Tissue Diseases

Fibromatosis, Aggressive

Aggression

Fibroma

Neoplasms, Fibrous Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Desmoid Tumor

Participants will take nirogacestat by mouth every day of each 28-day study cycle. Based on when you enroll in this study, you will take nirogacestat either 1 time a day at about the same time each day OR 2 times a day, about 12 hours apart.

Keila Torres, MD,PHD

Keila Torres, MD, PHD

To learn about the safety and effects of an investigational drug called nirogacestat when given to participants with a desmoid tumor/aggressive fibromatosis

Primary Objectives:

• To identify biomarkers associated with response and non-response to nirogacestat in participants with desmoid tumors (DT).

Secondary Objectives:

* To assess the 12-month progression-free survival (PFS of participants with DT who receive nirogacestat at 150 mg or 100 mg BID.
* To assess MRI volumetric and functional parameters associated with response and non-response to nirogacestat in participants with DT.
* To evaluate the histopathological changes in DT biopsy specimens.
* To evaluate the safety and tolerability of nirogacestat in participants with DT.

Exploratory Objectives:

* To assess clinical benefit and tumor response by additional MRI-based measurements including MRI-modified Choi criteria and WHO.
* To evaluate MRI parameters such as intensity histogram analysis from T2-weighted image (T2-WI), short inversion time inversion-recovery (T2-STIR), diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) mapping, post-contrast Water Dixon, perfusion-weighted imaging, and susceptibility-weighted imaging (SWI) with contrast and correlate with therapeutic response and clinical outcome.
* To assess the dynamics and concordance of circulating tumor cells (CTCs) in the blood compartment and tumor burden during nirogacestat treatment.
* To identify cell-free DNA (cfDNA) biomarkers associated with response and non-response to nirogacestat in patients with DT.
* To understand the impact of dose on the incidence of ovarian dysfunction in women of childbearing potential (WOCBP).

Evaluation of the Response and Non-response of Nirogacestat in Desmoid Tumors- Clinical Study

M.D. Anderson Cancer Center

There will be a 1:1 randomization betweennirogacestat 100 mg BID or 100 mg QD during the 4day run-in period prior to starting belantamab mafodotin on Cycle 1 Day 1 (days -4 to -1). The cycle length for Cycles 1-3 is 21 days (3 weeks). Treatment with nirogacestat will be 100 mg BID continuously during each cycle for all subjects. Belantamab mafodotin will be administered via IV infusion in an outpatient setting on Day 1 of Cycles 1-3 and nirogacestat 100mg BID will be administered continuously on Days 1-21 of each cycle. Treatment with belantamab mafodotin will be given at an initial dose of 1.0 mg/kg. The study will have a 3+3 dose escalation design for belantamab mafodotin. Belantamab mafodotin dose levels are 1.0 mg/kg, 1.4 mg/kg, and 1.9 mg/kg. Pomalidomide was added, 2 mg to the 1.4 mg/kg and 1.9 mg/kg dose cohorts.

Belantamab mafodotin will be administered via IV infusion in an outpatient setting on Day 1 of Cycles 1-3. Treatment with belantamab mafodotin will be given at an initial dose of 1.0 mg/kg. The study will have a 3+3 dose escalation design for belantamab mafodotin. Belantamab mafodotin dose levels are 1.0 mg/kg, 1.4 mg/kg, and 1.9 mg/kg

Belantamab Mafodotin

1:1 randomization between nirogacestat 100mg BID or 100 mg QD during the 4 day run-in period. Treatment with nirogacestat will be 100mg BID continuously during each cycle for all subjects.

After the 4-day run-in period, all patients will receive nirogacestat in combination with belantamab, mafodotin and pomalidomide. Pomalidomide was added for day 1-14 for cycle 1-3 and day 1-14 and day 21-35 for C4+.

Malin Hultcrantz, MD, PhD

Sham Mailankody, MBBS

Malin Hultcrantz, MD

The purpose of this study is to find out whether combination treatment with the study drugs belantamab mafodotin, nirogacestat, and pomalidomide is a safe treatment for people who have relapsed or refractory multiple myeloma. The researchers will test different doses of belantamab mafodotin to find the safest dose to give with nirogacestat and pomalidomide. The researchers also want to find out whether belantamab mafodotin plus nirogacestat and pomalidomide is an effective treatment for this type of bone marrow cancer, and the researchers will do tests that show whether the study treatment slows or stops the growth of cancer.

This is a phase Ib study with trial treatment is a combination of belantamab mafodotin (GSK2857916) and nirogacestat. A standard 3+3 dose escalation design with three planned doses of belantamab mafodotin will be implemented. There will be a 1:1 randomization between nirogacestat 100 mg BID or 100 mg QD during the 4 day run-in period prior to starting belantamab mafodotin on Cycle 1 Day 1 (days -4 to -1).

A Study of Belantamab Mafodotin in Combination With Nirogacestat and Pomalidomide in People With Multiple Myeloma That Has Not Responded to Treatment or Has Come Back After Treatment

Belantamab Mafodotin in Combination With Nirogacestat and Pomalidomide in Patients With Relapsed or Refractory Multiple Myeloma

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to:crdatashare@mskcc.org.

The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized.

Traditional Response Criteria from International Myeloma Working Group Criteria for Multiple Myeloma

Memorial Sloan Kettering Cancer Center

Anti-Obesity Agents

Vasoconstrictor Agents

Respiratory System Agents

Imidazole

Phenylpropanolamine

Guaifenesin

Chlorpheniramine, phenylpropanolamine drug combination

Patients receive nirogacestat PO BID on days 1-28. Cycles repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO and CT or MRI on study. Patients may also undergo x-ray imaging and blood sample collection on study.

Biospecimen Collection

Computed Tomography

Echocardiography

Magnetic Resonance Imaging

Quality-of-Life Assessment

Questionnaire Administration

X-Ray Imaging

Fariba Navid

This phase II trial studies the side effects and how well nirogacestat works in treating patients less than 18 years of age with desmoid tumors that has grown after at least one form of treatment by mouth or in the vein that cannot be removed by surgery. Nirogacestat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To estimate the 2-year progression-free survival (PFS) rate in patients with progressive, surgically unresectable desmoid tumor treated with nirogacestat.

II. To describe the toxicities of nirogacestat in children and adolescents with desmoid tumor.

III. To characterize the pharmacokinetics (PK) of nirogacestat in children and adolescents.

SECONDARY OBJECTIVE:

I. To determine the objective tumor response rate (ORR) of nirogacestat in children and adolescents with progressive, surgically unresectable desmoid tumor.

EXPLORATORY OBJECTIVES:

I. To collect blood, archival tumor samples and on-study/post-treatment tumor samples (if available) from patients enrolled on this trial to correlate various CTNNB1 and APC gene mutations and genomic signatures with tumor response and PFS.

II. To explore the effect of nirogacestat on immune cells and immunoglobulin levels in the peripheral blood.

III. To collect blood samples for banking at baseline, during treatment, and at the time of progression for future research.

IV. To compare assessment of tumor response using Response Evaluation Criteria in Solid Tumors (RECIST), World Health Organization (WHO) criteria, and T2 and volumetric changes using magnetic resonance imaging (MRI).

V. To utilize a tool developed to specifically assess patient reported outcomes (PROs) in adult patients with desmoid tumor (GOunder/DTRF DEsmoid Symptom/Impact Scale \[GODDESS\]) and the Patient Reported Outcomes Measurement Information System (PROMIS) to explore the relationship between PROs and tumor response and PFS.

OUTLINE:

Patients receive nirogacestat orally (PO) twice daily (BID) on days 1-28. Cycles repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography (ECHO) and computed tomography (CT) or MRI on study. Patients may also undergo x-ray imaging and blood sample collection on study.

After completion of study treatment, patients are followed up at 30 days.

A Study of a New Drug, Nirogacestat, for Treating Desmoid Tumors That Cannot be Removed by Surgery

A Safety, Pharmacokinetic and Efficacy Study of a y-Secretase Inhibitor, Nirogacestat (PF-03084014), in Children and Adolescents With Progressive, Surgically Unresectable Desmoid Tumors

The chi-square test will be used to assess the correlation of CTNNB1 and APC gene mutations and genomic signatures with tumor response, and the long-rank test will be used to assess the correlation of CTNNB1 and APC gene mutations and genomic signatures with PFS.

Lymphocyte subsets include CD3 (total T cells), CD3+CD4+ (T helper cells), CD3+CD8+ (T cytotoxic cells), CD3+HLA-DR+ (activated T cells) percentages and absolute counts and CD4:CD8 ratio. The chi-square test will be used to assess the correlation of the levels of lymphocyte and immunoglobulin with tumor response, and the Cox regression will be used to assess the correlation of the levels of lymphocyte and immunoglobulin with PFS.

The chi-square test will be used to assess the correlation of PROs summary scores with tumor response, and the Cox regression will be used to assess the correlation of PROs summary scores with PFS. Correlation between PRO summary scores using Patient Reported Outcomes Measurement Information System and GOunder/DTRF DEsmoid Symptom/Impact Scale will be assessed by performing inferences on the Pearson correlation coefficients.

Will be estimated using the Kaplan-Meier method with the 95% confidence interval estimated by the Peto-Peto method.

Will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. All grade 3 or above toxicities deemed related to study drug will be summarized. All grade 1 and 2 toxicities observed in \> 5% of participants and deemed related to study drug will be reported.

PK parameters of nirogacestat will be defined to quantify systemic exposure, drug clearance, terminal half-life and other pharmacokinetic characteristics. These PK parameters will be summarized with descriptive statistics, including means, medians, ranges, and standard deviations.

Defined by the rate of a complete response or partial response by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

National Cancer Institute (NCI)

Children's Oncology Group

Patients will receive 3-cycle lead-in with systemic therapy with nirogacestat 150 mg po BID, given continuously.

Nirogacestat 150 mg by mouth twice-daily continuously for Cycles 1 through 3. Treatment with nirogacestat may continue via this study protocol for up to 24 months (26 cycles of treatment), unless there is progression of disease, intolerance, start of new anticancer therapy, or Subject Study Completion or Termination occurs.

Cryoablation procedure (single session) of one tumor mass between Cycles 3 and 4 of nirogacestat treatment

Cryoablation

Behnaz P Agahian

Amir H Emami

Behnaz Agahian

Nam Bui, M.D.

Pejman Ghanouni, M.D.

Kristen Ganjoo, M.D.

The primary purpose of this protocol is Systemic therapy with oral study agent, nirogacestat, followed by a single cryoablation procedure.

The primary purpose of this protocol is treatment. Systemic therapy with oral study agent, nirogacestat, will be given for 3 cycles (1 cycle = 28 days) followed by a single cryoablation procedure between Cycles 3 and 4, and then continued nirogacestat for Cycles 4 through 26. Treatment with nirogacestat may continue via this study for up to 24 months (26 cycles of treatment), unless there is progression of disease, intolerance, subject withdraws their consent, start of a new anticancer therapy, or until Subject Study Completion or Termination occurs.

Study of Cryoablation and Nirogacestat for Desmoid Tumor

Phase II Study of Cryoablation and Nirogacestat for Desmoid Tumor

Clinical benefit (CB) is defined as the number of participants assessed with a complete response (CR), partial response (PR), or stable disease (SD) within 1 year and with no evidence of loss of response nor progression within that year. Response \& progression will be assessed according to the Revised Response Evaluation Criteria in Solid Tumors (RECIST)v1.1, as follows:

RECIST v1.1:

* CR=Disappearance of all lesions
* PR=≥30% decrease in diameter of target lesions
* Progressive disease (PD)=20% increase in diameter of target lesion; progression of non-target lesion; or ≥1 new lesion(s)

For the overall outcome:

* SD=Changes not meeting above criteria
* Overall Response (OR)=CR+PR
* CB=CR+PR+SD

Clinical benefit (CB) is defined as the number of participants assessed with a complete response (CR), partial response (PR), or stable disease (SD) within

1 year and with no evidence of loss of response nor progression within that year.

Response \& progression will be assessed according to the modified Revised Response Evaluation Criteria in Solid Tumors (mRECIST), as follows.

CR=Disappearance of intratumoral enhancement

* PR=≥ 30% decrease in the diameter of target lesion(s)
* PD=An increase of \>20% in the diameter of target lesion. The outcome is the number of participants alive after 1 year and without PD per mRECIST, a number without dispersion

Progressive-free survival (PFS) is an assessment of the number of participants at a specific time who remain alive and without tumor progression. Progressive disease (PD) will be assessed according to Revised Response Evaluation Criteria in Solid Tumors (RECIST)v1.1, or, for tumors assessed with MRI enhancement, modified RECIST (mRECIST) defined as follows:

RECIST v1.1:

* PD=20% increase in diameter of target lesion; progression of non-target lesion; or ≥1 new lesion(s) mRECIST:
* PD=An increase of \>20% in the diameter of target lesion. The outcome is the number of participants alive after 1 year and without PD per RECIST or mRECIST, a number without dispersion.

Objective response (OR) is defined as the number of participants assessed with a complete response (CR) or partial response (PR) within 1 year and with no evidence of loss of response nor progression within that year. Response \& progression will be assessed according to the Revised Response Evaluation Criteria in Solid Tumors (RECIST)v1.1, or, for assessed with MRI enhancement, modified RECIST (mRECIST).

Time-to-response (TTR) is an assessment of the length of time from the start of treatment until clinical response (complete response, CR; or partial response, PR) is documented.in accordance with the Revised Response Evaluation Criteria in Solid Tumors (RECIST)v1.1, or, for assessed with MRI enhancement, modified RECIST (mRECIST) defined as follows:'

RECIST v1.1:

* CR=Disappearance of all lesions
* PR=≥30% decrease in diameter of target lesions Progressive disease (PD)=20% increase in diameter of target lesion; progression of non-target lesion; or ≥1 new lesion(s) mRECIST:
* CR=Disappearance of intratumoral enhancement
* PR=≥ 30% decrease in the diameter of target lesion(s) PD=An increase of \>20% in the diameter of target lesion.

For either:

• SD=Changes not meeting above criteria The outcome is expressed as the median TTR (by RECIST or mRECIST), with standard deviation.

Duration of response (DoR) is defined as the time from the date of documented disease response (complete response, CR; or partial response, PR) to the date of the first documented disease progression. CR and PR will be assessed according to the Revised Response Evaluation Criteria in Solid Tumors (RECIST)v1.1, or, for assessed with MRI enhancement, modified RECIST (mRECIST) as RECIST v1.1.

Safety is assessed as the number of adverse events determined by the investigator to be possibly, probably, or definitely related to nirogacestat treatment (ie, drug toxicities). All related events will be collected and reported. Adverse events of Grade 3 (severe) are considered notable and potentially actionable during treatment, while adverse events Grade 1 or 2 are considered routine, with typically little or no change in treatment needed. The outcome will be reported as the number of related adverse events Grade 3 or higher is a number without dispersion.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Teclistamab With Other Anticancer Therapies in Participants With Multiple Myeloma	NCT04722146	Multiple Myelom...	Teclistamab Daratumumab Pomalidomide Lenalidomide Bortezomib Nirogacestat	18 Years -	Janssen Research & Development, LLC
Nirogacestat in Ovarian Granulosa Cell Tumors	NCT05348356	Ovarian Granulo... Ovarian Granulo... Ovarian Cancer	Nirogacestat	18 Years -	SpringWorks Therapeutics, Inc.
Evaluation of the Response and Non-response of Nirogacestat in Desmoid Tumors- Clinical Study	NCT05879146	Tumor	Nirogacestat	18 Years -	M.D. Anderson Cancer Center
A Study of Belantamab Mafodotin in Combination With Nirogacestat and Pomalidomide in People With Multiple Myeloma That Has Not Responded to Treatment or Has Come Back After Treatment	NCT05556798	Multiple Myelom...	Belantamab Mafo... Nirogacestat Pomalidomide	18 Years -	Memorial Sloan Kettering Cancer Center
A Study of a New Drug, Nirogacestat, for Treating Desmoid Tumors That Cannot be Removed by Surgery	NCT04195399	Desmoid Fibroma... Recurrent Desmo... Unresectable De...	Biospecimen Col... Computed Tomogr... Echocardiograph... Magnetic Resona... Nirogacestat Quality-of-Life... Questionnaire A... X-Ray Imaging	12 Months - 18 Years	Children's Oncology Group
A Study of Teclistamab With Other Anticancer Therapies in Participants With Multiple Myeloma	NCT04722146	Multiple Myelom...	Teclistamab Daratumumab Pomalidomide Lenalidomide Bortezomib Nirogacestat	18 Years -	Janssen Research & Development, LLC
Study of Cryoablation and Nirogacestat for Desmoid Tumor	NCT05949099	Desmoid Tumor	Nirogacestat Cryoablation	18 Years -	Stanford University

Spots Global Cancer Trial Database for nirogacestat

Every month we try and update this database with for nirogacestat 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.