Trial · NCT03785964

Nirogacestat for Adults With Desmoid Tumor/Aggressive Fibromatosis (DT/AF)

NCT03785964, Phase 3, Completed, SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany; results first posted 2024-06-12

3 sourcestrials-2026-11-12-0.5.0

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ConductScience Library. Nirogacestat for Adults With Desmoid Tumor/Aggressive Fibromatosis (DT/AF). Trials, record NCT03785964. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT03785964

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Trial

As registered on ClinicalTrials.gov, in the graph's capture of the registry.

Title: Nirogacestat for Adults With Desmoid Tumor/Aggressive Fibromatosis (DT/AF)
NCT number: NCT03785964
Status: Completed
Phases: Phase 3
Enrollment: 142 participants, actual
Lead sponsor: SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany
Conditions: Desmoid Tumor, Aggressive Fibromatosis
Interventions: Nirogacestat oral tablet, Placebo Oral Tablet
First posted: 2018-12-24
Last updated: 2026-08-20
Results first posted: 2024-06-12

Source ClinicalTrials.gov

Registered outcomes8

Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.

List	Outcome	Time frame	Description
Primary	Progression Free Survival (PFS) Defined as the Time From Randomization Until Date of Assessment of Progression or Death by Any Cause.	On the first day of every 3 cycles (each cycle is 28 days) until disease progression is observed or death, whichever comes first, assessed up to approximately 2 years	Progression will be determined radiographically using RECIST v1.1 (Eisenhauer, 2009) or clinically as assessed by the investigator. Clinical progression is defined as the onset or worsening of symptoms resulting in a global deterioration of health status causing the permanent discontinuation from study treatment and the initiation of emergent treatment (e.g., radiotherapy, surgery, or systemic therapy including chemotherapy or tyrosine kinase inhibitors) for DT/AF. Events of clinical progression will be adjudicated by an independent blinded central Endpoint Adjudication Committee (EAC) which will qualify events of clinical progression for inclusion in the PFS endpoint prior to study unblinding according to an EAC Review Charter.
Secondary	Objective Response Rate Using RECIST Version 1.1 Criteria.	On the first day of every 3 cycles (each cycle is 28 days) through study completion, an average of 2 years	Objective response rate (ORR) is defined as the proportion of participants having a confirmed Best Overall Response (BOR) of CR or PR by central reader using RECIST v1.1 criteria. Responses obtained up until progression, or last evaluable assessment in the absence of progression, will be included in the assessment of ORR. However, any responses, which occurred after a new anticancer therapy was received, will not be included. ORR is presented by percentages of responders.
Secondary	Change From Baseline at Cycle 10 in the Brief Pain Inventory (BPI) Average Pain Intensity (API) Score.	Daily for the last 7 days of every cycle (each cycle is 28 days) through study completion, an average of 2 years	The Brief Pain Inventory consists of 9 questions and utilizes a 11-point Numerical pain Rating Scale from 0-10 measuring severity from "no pain" to "pain as bad as you can imagine," with a 24-hour recall period. Average Pain Intensity is calculated as the 7-day average (when results on at least 4 days for a VISIT are available) of Brief Pain Inventory Question #3 - Worst Pain in last 24 hours. A lower score indicates greater pain relief. The minimum and maximum of the actual score are (0, 8) for Nirogacestat and (0,9) for Placebo, respectively. A positive change from Baseline value indicates worsening of Average Pain Intensity and a negative change from Baseline value indicates improvement of Average Pain Intensity. The minimum and maximum of change from baseline score are (-7, 3) for Nirogacestat and (-5, 5) for Placebo, respectively.
Secondary	Change From Baseline at Cycle 10 in the GOunder/Desmoid Tumor Research Tumor Foundation (DTRF) DEsmoid Tumor Symptom Scale (DTSS) - Total Score	Daily for the last 7 days of every cycle (each cycle is 28 days) through study completion, an average of 2 years	The DEsmoid Tumor Symptom Scale is an 11-point, numeric rating scale from 0 to 10 to measure severity from "none" to "as bad as you can imagine," with a 24-hour recall period. The Total Symptom Score is calculated as the mean of Pain items (Items 1-3) as a single score, then a mean of this with items 4-7). Weekly summary scores will be created by averaging the daily scores over the 7 days period prior to each visit. A weekly score will be derived only if 4 or more out of 7 days period have non-missing scores. The weekly summary score will be used in analyses. If no weekly summary score is calculable, the participant will have data considered as missing at that visit. Higher scores represent worse symptom severity. The minimum and maximum of the actual score are (0,7) for Nirogacestat and (0,10) for Placebo. A positive change from Baseline value indicated worsening of symptoms. The minimum and maximum of change from baseline are (-6,1) for Nirogacestat and (-4,5) for Placebo.
Secondary	Change From Baseline in the GOunder/Desmoid Tumor Research Foundation (DTRF) DEsmoid Tumor Impact Scale (DTIS) - Physical Functioning Domain Score	On the last day of every cycle (each cycle is 28 days) through study completion, average of 2 years.	The items are evaluated on a 5-point Likert Scale ranging from "none of the time" to "all of the time" to measure frequency, with a 7-day recall period. The Physical Function Domain Score are calculated as the average Item 01 Moving, Item 02 Reaching (Freq), Item 06 Vigorous Activity, Item 7 Moderate Activity, and Item 08 Accomplished Less. Higher scores represent worst impact severity. The minimum and maximum of the actual score are (1, 5) for Nirogacestat and (1,5) for Placebo, respectively. A positive change from baseline value indicates worsening impact and a negative change from baseline value indicates improvement in impact. The minimum and maximum of change from baseline score are (-3, 0) for Nirogacestat and (-1, 2) for Placebo, respectively.
Secondary	Change From Baseline at Cycle10 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (GHS/QoL) Scale.	Last day of every cycle (each cycle is 28 days) through study completion, an average of 2 years	The EORTC Quality of Life Questionnaire-Core 30 version 3.0 was used with a 7-day recall period. It consists of 30 questions with all items scored 1 ("not at all") to 4 ("very much") except for the 2 items contributing to the global health status/QoL, which are scored 1 ("very poor") to 7 ("excellent"). The instrument yields the following scales:5 functional scales, 3 symptom scales, and a global health status/quality of life scale. A high score for the global health status/QoL represents a high QoL. The minimum and maximum of the actual score are (33, 100) for Nirogacestat and (8,92) for Placebo, respectively. A positive change from baseline indicated improvement of global health status and a negative change from baseline value indicated worsening of global health status. The minimum and maximum of change from baseline score are (-58, 67) for Nirogacestat and (-67, 42) for Placebo, respectively.
Secondary	Change From Baseline at Cycle 10 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Physical Functioning	Last day of every cycle (each cycle is 28 days) through study completion, an average of 2 years	The EORTC Quality of Life Questionnaire-Core 30 version 3.0 was used with a 7-day recall period. It consists of 30 questions with all items scored 1 ("not at all") to 4 ("very much") except for the 2 items contributing to the global health status/QoL, which are scored 1 ("very poor") to 7 ("excellent"). The instrument yields the following scales:5 functional scales, 3 symptom scales, and a global health status/quality of life scale. A high score for a Physical functional scale represents a high/healthy level of functioning. The minimum and maximum of the actual score are (27, 100) for Nirogacestat and (7,100) for Placebo, respectively. A positive change from baseline indicated improvement of global health status and a negative change from baseline value indicated worsening of physical functioning scores. The minimum and maximum of change from baseline score are (-7, 40) for Nirogacestat and (-40, 27) for Placebo, respectively.
Secondary	Change From Baseline at Cycle 10 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Role Functioning.	Last day of every cycle (each cycle is 28 days) through study completion, an average of 2 years	The EORTC Quality of Life Questionnaire-Core 30 version 3.0 was used with a 7-day recall period. It consists of 30 questions with all items scored 1 ("not at all") to 4 ("very much") except for the 2 items contributing to the global health status/QoL, which are scored 1 ("very poor") to 7 ("excellent"). The instrument yields the following scales:5 functional scales, 3 symptom scales, and a global health status/quality of life scale. A positive change from baseline indicated improvement of global health status and a negative change from baseline value indicated worsening of global health status and functioning scores. The minimum and maximum of change from baseline score are (-17, 83) for Nirogacestat and (-100, 50) for Placebo, respectively.

Source ClinicalTrials.gov

Outcomes8

Each outcome the trial posted results for, in ClinicalTrials.gov's words.

Type	Outcome	Time frame	Population	Units	Measured as
PRIMARY	Progression Free Survival (PFS) Defined as the Time From Randomization Until Date of Assessment of Progression or Death by Any Cause.	On the first day of every 3 cycles (each cycle is 28 days) until disease progression is observed or death, whichever comes first, assessed up to approximately 2 years	Intent-to-Treat Population (All Randomized)	Months	MEDIAN
SECONDARY	Objective Response Rate Using RECIST Version 1.1 Criteria.	On the first day of every 3 cycles (each cycle is 28 days) through study completion, an average of 2 years	Intent-to-Treat Population (All Randomized)	percentage of participants	NUMBER
SECONDARY	Change From Baseline at Cycle 10 in the Brief Pain Inventory (BPI) Average Pain Intensity (API) Score.	Daily for the last 7 days of every cycle (each cycle is 28 days) through study completion, an average of 2 years	Intent-to-Treat Population	score on a scale	LEAST_SQUARES_MEAN
SECONDARY	Change From Baseline at Cycle 10 in the GOunder/Desmoid Tumor Research Tumor Foundation (DTRF) DEsmoid Tumor Symptom Scale (DTSS) - Total Score	Daily for the last 7 days of every cycle (each cycle is 28 days) through study completion, an average of 2 years	Intent-to-Treat Population	score on a scale	LEAST_SQUARES_MEAN
SECONDARY	Change From Baseline in the GOunder/Desmoid Tumor Research Foundation (DTRF) DEsmoid Tumor Impact Scale (DTIS) - Physical Functioning Domain Score	On the last day of every cycle (each cycle is 28 days) through study completion, average of 2 years.	Intent-to-Treat Population	score on a scale	LEAST_SQUARES_MEAN
SECONDARY	Change From Baseline at Cycle10 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (GHS/QoL) Scale.	Last day of every cycle (each cycle is 28 days) through study completion, an average of 2 years	Intent-to-Treat Population	score on a scale	LEAST_SQUARES_MEAN
SECONDARY	Change From Baseline at Cycle 10 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Physical Functioning	Last day of every cycle (each cycle is 28 days) through study completion, an average of 2 years	Intent-to-Treat Population	score on a scale	LEAST_SQUARES_MEAN
SECONDARY	Change From Baseline at Cycle 10 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Role Functioning.	Last day of every cycle (each cycle is 28 days) through study completion, an average of 2 years	Intent-to-Treat Population	score on a scale	LEAST_SQUARES_MEAN

Source ClinicalTrials.gov

Results by group16

Each measurement the trial posted, group by group, in the words and numbers it posted.

Outcome	Group	Value	Spread	Units
Progression Free Survival (PFS) Defined as the Time From Randomization Until Date of Assessment of Progression or Death by Any Cause.	Double-Blind Phase - Nirogacestat	NA	95% Confidence Interval NA to NA	Months
Progression Free Survival (PFS) Defined as the Time From Randomization Until Date of Assessment of Progression or Death by Any Cause.	Double-Blind Phase - Placebo	15.1	95% Confidence Interval 8.4 to NA	Months
Objective Response Rate Using RECIST Version 1.1 Criteria.	Double-Blind Phase - Nirogacestat	41	95% Confidence Interval 29.8 to 53.8	percentage of participants
Objective Response Rate Using RECIST Version 1.1 Criteria.	Double-Blind Phase - Placebo	8	95% Confidence Interval 3.1 to 17.3	percentage of participants
Change From Baseline at Cycle 10 in the Brief Pain Inventory (BPI) Average Pain Intensity (API) Score.	Double-Blind Phase - Nirogacestat	-1.583	95% Confidence Interval -2.157 to -1.009	score on a scale
Change From Baseline at Cycle 10 in the Brief Pain Inventory (BPI) Average Pain Intensity (API) Score.	Double-Blind Phase - Placebo	-0.241	95% Confidence Interval -0.822 to 0.340	score on a scale
Change From Baseline at Cycle 10 in the GOunder/Desmoid Tumor Research Tumor Foundation (DTRF) DEsmoid Tumor Symptom Scale (DTSS) - Total Score	Double-Blind Phase - Nirogacestat	-1.110	95% Confidence Interval -1.569 to -0.651	score on a scale
Change From Baseline at Cycle 10 in the GOunder/Desmoid Tumor Research Tumor Foundation (DTRF) DEsmoid Tumor Symptom Scale (DTSS) - Total Score	Double-Blind Phase - Placebo	0.457	95% Confidence Interval -0.009 to 0.923	score on a scale
Change From Baseline in the GOunder/Desmoid Tumor Research Foundation (DTRF) DEsmoid Tumor Impact Scale (DTIS) - Physical Functioning Domain Score	Double-Blind Phase - Nirogacestat	-0.613	95% Confidence Interval -0.808 to -0.418	score on a scale
Change From Baseline in the GOunder/Desmoid Tumor Research Foundation (DTRF) DEsmoid Tumor Impact Scale (DTIS) - Physical Functioning Domain Score	Double-Blind Phase - Placebo	0.094	95% Confidence Interval -0.113 to 0.300	score on a scale

1 to 10 of 16Source ClinicalTrials.gov

See all 16 results by group

Participant flow8

How many started, completed or left each group, period by period.

Period	Milestone	Group	Participants
Overall Study	STARTED	Double-Blind Phase - Nirogacestat	70
Overall Study	STARTED	Double-Blind Phase - Placebo	72
Overall Study	Treated (Safety Population)	Double-Blind Phase - Nirogacestat	69
Overall Study	Treated (Safety Population)	Double-Blind Phase - Placebo	72
Overall Study	COMPLETED	Double-Blind Phase - Nirogacestat	12
Overall Study	COMPLETED	Double-Blind Phase - Placebo	35
Overall Study	NOT COMPLETED	Double-Blind Phase - Nirogacestat	58
Overall Study	NOT COMPLETED	Double-Blind Phase - Placebo	37

Source ClinicalTrials.gov

Adverse events192

Each adverse event the trial posted, group by group: the participants affected out of those at risk.

Type	Event	Organ system	Group	Affected	At risk	Events
other	Anaemia	Blood and lymphatic system disorders	Double-Blind Phase - Nirogacestat	7	69	16
other	Anaemia	Blood and lymphatic system disorders	Double-Blind Phase - Placebo	8	72	18
other	Abdominal distension	Gastrointestinal disorders	Double-Blind Phase - Nirogacestat	4	69	4
other	Abdominal distension	Gastrointestinal disorders	Double-Blind Phase - Placebo	3	72	4
other	Abdominal pain	Gastrointestinal disorders	Double-Blind Phase - Nirogacestat	11	69	16
other	Abdominal pain	Gastrointestinal disorders	Double-Blind Phase - Placebo	9	72	18
other	Abdominal pain upper	Gastrointestinal disorders	Double-Blind Phase - Nirogacestat	5	69	6
other	Abdominal pain upper	Gastrointestinal disorders	Double-Blind Phase - Placebo	1	72	1
other	Constipation	Gastrointestinal disorders	Double-Blind Phase - Nirogacestat	7	69	9
other	Constipation	Gastrointestinal disorders	Double-Blind Phase - Placebo	7	72	8

1 to 10 of 192Source ClinicalTrials.gov

See all 192 adverse events

Adverse event totals6

The totals the trial posted for each group.

Total	Group	Affected	At risk
Total, all-cause mortality	Double-Blind Phase - Nirogacestat	0	69
Total, all-cause mortality	Double-Blind Phase - Placebo	1	72
Total, other adverse events	Double-Blind Phase - Nirogacestat	69	69
Total, other adverse events	Double-Blind Phase - Placebo	69	72
Total, serious adverse events	Double-Blind Phase - Nirogacestat	14	69
Total, serious adverse events	Double-Blind Phase - Placebo	8	72

Source ClinicalTrials.gov

Papers3

The papers the trial lists on ClinicalTrials.gov.

PMID	Listed as	Source
36884323	DERIVED	PubMed
37347393	DERIVED	PubMed
41115259	DERIVED	PubMed

Grants0

The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.

None in this release.

Trial comparisons2

Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.

Comparison	Source
Double-Blind Phase - Nirogacestat vs Double-Blind Phase - Placebo: deaths from any cause	Trial comparisons
Double-Blind Phase - Nirogacestat vs Double-Blind Phase - Placebo: serious adverse events	Trial comparisons

Tests0

The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.

None in this release.

Data dates

The day each source was copied for this release.

ClinicalTrials.gov: 2026-11-12; ClinicalTrials.gov
Results, from AACT: 2026-03-23; AACT
NIH grant links: 2026-11-13; NIH RePORTER

Sources 3

ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
ClinicalTrials.govNo license stated
NIH RePORTER's clinical studies and project filesPublic domain

Each source's terms

ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
ClinicalTrials.govnone stated
NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)

ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.

For software

Read this trial from software.

The record and each of its lists are JSON, twenty rows a page. No key.

GET https://conductscience.org/api/trials/v1/NCT03785964

GET https://conductscience.org/api/trials/v1/NCT03785964/events?page=2

API reference For AI assistants