VAREGACESTAT for Desmoid tumour|Aggressive fibromatosis

Inclusion criteria

• {"criterion_text":"- Part A: At least 18 years of age (inclusive) at the time of signing the ICF\n- Part B: Histologically confirmed desmoid tumor (aggressive fibromatosis) by local pathologist (prior to informed consent) that has progressed per RECIST v1.1 (≥20% or new lesion) by investigator within 12 months of the screening visit scan.\n- Part B: Evidence of measurable disease by CT/MRI scan. Measurable lesions are defined according to RECIST v1.1\n- Part B: One of the following: • Recurrent/refractory disease following at least one line of therapy (including surgery, radiation, or systemic therapy); OR • Treatment naïve subjects for whom, in the opinion of the investigator, surgery or radiation therapy is not deemed appropriate;\n- Part B: A desmoid tumor in which continued progressing disease will not result in immediate significant risk to the subject.\n- Part B: Agrees to provide FFPE archival or fresh tumor tissue\n- Part B: Must be able to swallow whole capsules with no GI condition affecting absorption (not including history of colectomy or proctocolectomy); nasogastric or G-tube administration is not allowed\n- OLE: One of the following: a. Participated in Part A (including MRI at Week 16) and were still on study at time that Part B/OLE dose selection was made, OR b. Participating in Part B and were noted to have radiographic progressive disease by BICR, OR c. Are on study treatment (placebo or varegacestat) after completion of Part B\n- OLE: Must be able to swallow whole capsules with no GI condition affecting absorption; nasogastric or G-tube administration is not allowed\n- OLE: Subject and/or legally authorized representative (i.e. parent/guardian) must be capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF.\n- OLE: Minor subjects must be capable of giving written assent as appropriate per the applicable age (per local regulatory requirements).\n- Part A: Histologically confirmed desmoid tumor (aggressive fibromatosis) by local pathologist (prior to informed consent).\n- Other protocol defined inclusion criteria could apply\n- Part A: Disease progression, assessed by the investigator, defined as having at least one of the following: a) Unidimensional growth of desmoid tumor(s) by ≥10%, using the sum of the largest diameters of target lesion(s), within 18 months of the screening MRI b) Having desmoid tumor-related pain that is not adequately controlled with non-opioid medication\n- Part A: At least 1 measurable lesion amenable to volume measurements by MRI at screening\n- Part A: One of the following: • Treatment naïve subjects for whom, in the opinion of the investigator, the IP is deemed appropriate; OR • Recurrent/refractory disease following at least one line of therapy(including surgery, radiation, or systemic therapy).\n- Part A: A desmoid tumor in which continued progressing disease will not result in immediate significant risk to the subject\n- Part A: Agrees to provide formalin-fixed paraffin embedded (FFPE) archival or fresh tumor tissue.\n- Part A: Must be able to swallow whole capsules with no GI condition affecting absorption (not including history of colectomy); nasogastric or G-tube administration is not allowed.\n- Part B: 1. ≥12 years of age (inclusive) in countries which allow participation of adolescents and ≥ 40 kg at the time of signing the ICF."}

Exclusion criteria

• {"criterion_text":"- Part A: Diagnosed with a malignancy in the past 2 years, unless for protocol defined allowed malignancies\n- Part A: ECG Exclusions: a. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥450 msec; b. QRS duration > 110 ms; c. PR interval > 240 ms; d. Marked ST-T wave abnormalities which would make it difficult to measure the QT interval\n- Part B: Diagnosed with a malignancy in the past 2 years, unless for protocol defined allowed malignancies\n- Part B: Current or recent (within 2 months of IP administration) GI disease or disorders that increase the risk of diarrhea, such as inflammatory bowel disease and Crohn's disease\n- Part B: Evidence of uncontrolled, active infection, requiring systemic antibacterial, anti-viral or anti-fungal therapy ≤7 days prior to administration of IP\n- Part B: Myocardial infarction within 6 months prior to enrollment, greater than Class 1 angina pectoris, or has NYHA Class III or IV heart failure, symptomatic ventricular arrhythmias, sustained ventricular tachycardia, TdP, the long QT syndrome, pacemaker dependence, or electrocardiographic evidence of acute ischemia\n- Part B: History of additional risk factors for TdP\n- Part B: Unstable or severe uncontrolled medical condition or any important medical illness or abnormal laboratory finding\n- Part B: Pregnant or breastfeeding or expecting to conceive children during the study\n- Part B: ECOG performance status ≥2\n- Part B: Abnormal organ and marrow function at Screening defined as: a.Neutrophils <1500/mm3; b. Platelet count <100,000/mm3; c.Hemoglobin <9 g/dL; d. Electrolytes (potassium, calcium, magnesium,and phosphorus, using corrected value if low serum albumin level is present) outside the normal limits of the local laboratory; e. Total bilirubin >1.5x ULN (except known Gilbert's syndrome >3x ULN); f. AST and ALT >2.5x ULN; g. Serum or plasma creatinine > ULN and CrCl <60 mL/min (calculation of CrCl will be based on acceptable institution standard); h.Uncontrolled triglyceride ≥Grade 2 elevations per CTCAE v5.0 (>300 mg/dL or >3.42 mmol/L); i.Any other laboratory abnormality ≥Grade 3\n- Part A: Current or recent (within 2 months of IP administration) GI disease or disorders that increase the risk of diarrhea, such as inflammatory bowel disease and Crohn's disease\n- Part B: ECG Exclusions: a. Mean QTcF ≥450 msec; b. Second or third degree AV block\n- OLE: Unstable or severe uncontrolled medical condition or any important medical illness, abnormal ECG or laboratory finding.\n- OLE: Ongoing TEAE from Part A or Part B that requires discontinuation\n- OLE: Breastfeeding or expecting to conceive children within the projected duration of the study\n- OLE: Use of any therapy that is prohibited in Part A or Part B of the study.\n- OLE: Concurrent enrollment in another clinical study unless it is an observational (non-interventional) clinical study\n- OLE: Hypersensitivity to AL102 and any of its excipients\n- Other protocol defined exclusion criteria could apply\n- Part A: Evidence of uncontrolled, active infection, requiring systemic antibacterial, anti-viral or anti-fungal therapy ≤7 days prior to administration of IP\n- Part A: Myocardial infarction within 6 months prior to enrollment, greater than Class 1 angina pectoris, or has NYHA Class III or IV heart failure, symptomatic ventricular arrhythmias, sustained ventricular tachycardia, TdP, the long QT syndrome, pacemaker dependence, or electrocardiographic evidence of acute ischemia\n- Part A: History of additional risk factors for TdP\n- Part A: Unstable or severe uncontrolled medical condition or any important medical illness or abnormal laboratory finding\n- Part A: Pregnant or breastfeeding or expecting to conceive children during the study\n- Part A: ECOG performance status ≥2\n- Part A: Abnormal organ and marrow function at Screening defined as: a. Neutrophils <1500/mm3; b. Platelet count <100,000/mm3; c. Hemoglobin <9 g/dL; d. Electrolytes (potassium, calcium, magnesium and phosphorus, using corrected value if low serum albumin level is present) outside the normal limits of the local laboratory; e. Total bilirubin >1.5x ULN (except known Gilbert's syndrome >3x ULN); f. AST and ALT >2.5x ULN; g. Serum or plasma creatinine > ULN and creatinine clearance (CrCl) <60 mL/min; h. Uncontrolled triglyceride ≥Grade 2 elevations per CTCAE v5.0 (>300 mg/dL or >3.42 mmol/L)"}

Primary endpoints

• {"endpoint_text":"- Part A: Frequency and severity of TEAEs and SAEs; time to treatment discontinuation due to TEAE","definition_or_measurement_approach":"Frequency and severity of TEAEs and SAEs as reported/recorded during study; time to treatment discontinuation measured as time from first dose to discontinuation due to TEAE (no additional measurement detail provided in source)."}
• {"endpoint_text":"- Part B: Progression free survival","definition_or_measurement_approach":"Defined as the time from randomization until the date of radiographic progression by Blinded Independent Central Review (BICR) or clinical progression (as specified elsewhere in endpoints)."}
• {"endpoint_text":"- OLE: Frequency and severity of TEAEs and SAEs","definition_or_measurement_approach":"Frequency and severity of TEAEs and SAEs as reported/recorded during the Open Label Extension (no additional measurement detail provided in source)."}

Secondary endpoints

• {"endpoint_text":"- Part A: change from baseline to week 16 in tumor volume","definition_or_measurement_approach":"Change from baseline to Week 16 in tumor volume as measured by MRI (volume measurements) per protocol."}
• {"endpoint_text":"- Part B: proportion of subjects with confirmed ORR","definition_or_measurement_approach":"Proportion with confirmed Overall Response Rate (ORR); evaluation by BICR based on RECIST v1.1 for tumor response (where specified elsewhere)."}
• {"endpoint_text":"- Part B: duration of response","definition_or_measurement_approach":"Duration of Response (DOR) measured from first documented confirmed response to disease progression or death (as defined in OLE secondary endpoints)."}
• {"endpoint_text":"- Part B: PFS as defined as the time from randomization until the date of radiographic progression by BICR or clinical progression","definition_or_measurement_approach":"PFS defined as time from randomization to radiographic progression by BICR or clinical progression."}
• {"endpoint_text":"- Part B: Change from baseline at Week 24 in estimated tumor volume","definition_or_measurement_approach":"Change from baseline in estimated tumor volume at Week 24 (measurement method via imaging as per protocol)."}
• {"endpoint_text":"- Part B: Change from baseline to Week 12 in the worst pain intensity (WPI)","definition_or_measurement_approach":"Change from baseline to Week 12 in Worst Pain Intensity (WPI) assessed using patient-reported measures (GODDESS instruments referenced elsewhere)."}
• {"endpoint_text":"- Part B: frequency and severity of TEAEs and SAEs","definition_or_measurement_approach":"As recorded during Part B; frequency and severity per CTCAE/recording procedures."}
• {"endpoint_text":"- Part B: time to treatment discontinuation due to TEAE","definition_or_measurement_approach":"Time from first dose to treatment discontinuation due to TEAE."}
• {"endpoint_text":"- OLE: PFS as defined as the time of radiographic progression","definition_or_measurement_approach":"PFS in OLE defined as time to radiographic progression (assessment by BICR when applicable)."}
• {"endpoint_text":"- OLE: Proportion of subjects with confirmed ORR (CR and PR) by BICR based on RECIST v1.1","definition_or_measurement_approach":"Proportion with confirmed Complete Response (CR) or Partial Response (PR) by BICR using RECIST v1.1."}
• {"endpoint_text":"- OLE: DOR as defined by the time from confirmed OOR (CR or PR) by BICR based on RECIST v1.1 until the earlier of the first documentation of disease progression or death from any cause","definition_or_measurement_approach":"Duration of Response per RECIST v1.1 by BICR from confirmed response to progression or death."}
• {"endpoint_text":"- OLE: PFS as defined as the time to radiographic progression as assessed by BICR based on RECIST v1.1, OR clinical progression","definition_or_measurement_approach":"PFS in OLE measured to radiographic progression by BICR (RECIST v1.1) or clinical progression."}
• {"endpoint_text":"- OLE: Change from baseline (defined as from the start of AL102 treatment) in − Quality of life as determined by GODDESS DTSS Total Symptom Score − GODDESS DTIS Physical Functioning Domain Score − WPI using GODDESS DTSS Item 1","definition_or_measurement_approach":"Change from AL102 treatment start in patient-reported outcomes: GODDESS DTSS total symptom score, GODDESS DTIS physical functioning domain score, and WPI (item 1 of GODDESS DTSS)."}

Netherlands

Latest Decision Or Authorization Date

30-10-2024

Number Of Sites

2

Number Of Participants

4

Poland

Latest Decision Or Authorization Date

09-12-2024

Number Of Sites

1

Number Of Participants

20

Belgium

Latest Decision Or Authorization Date

30-10-2024

Number Of Sites

1

Number Of Participants

1

Germany

Latest Decision Or Authorization Date

13-11-2024

Number Of Sites

2

Number Of Participants

11

Italy

Latest Decision Or Authorization Date

19-11-2024

Number Of Sites

2

Number Of Participants

9

Spain

Latest Decision Or Authorization Date

12-11-2024

Number Of Sites

5

Number Of Participants

18

Primary sponsor

Full Name

Immunome Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

PPD Development LP

Responsibilities

PK analysis

Name

IQVIA Limited

Responsibilities

Multiple operational roles (various trial support functions listed in CTIS sponsor duties)

Name

Q Squared Solutions LLC / Q Squared Solutions Limited

Responsibilities

Tumor tissue analysis; sample processing and storage

Name

Eresearchtechnology Inc. (Clario)

Responsibilities

ECG analysis/review, Holter monitoring

Name

Almac Pharma Services Limited

Responsibilities

PD analysis

Name

Imaging Endpoints II LLC

Responsibilities

Medical image analysis/review

Name

Tempus Labs Inc.

Responsibilities

Genomic analysis

Name

Mayo Collaborative Services LLC

Responsibilities

AMH testing

Third parties

• {"country":"United States","full_name":"Q Squared Solutions LLC","duties_or_roles":"tumor tissue analysis; sample processing and storage","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"PK analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"tumor tissue analysis; sample processing and storage","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Imaging Endpoints II LLC","duties_or_roles":"Medical image analysis/review - X-ray, MRI, ultrasound, etc.","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Alcura Health Espana S.A.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"ECG analysis/review, Holter monitoring","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Almac Pharma Services Limited","duties_or_roles":"PD analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Tempus Labs Inc.","duties_or_roles":"Genomic analysis","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Mayo Collaborative Services LLC","duties_or_roles":"AMH testing","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}