CAMURUS

HS-19-657

Camurus AB

Adult male or female patients with histologically confirmed, advanced (unresectable and/or metastatic), and well-differentiated NET of presumed GEP origin.

A randomized, multi-center, open-label, active-controlled Phase 3 trial

Phase III study

Trial Population
Adult male or female patients with histologically confirmed, advanced (unresectable and/or metastatic), and well-differentiated NET of presumed GEP origin.
Number of Patients (Planned)
Approximately 300 patients will be randomized with approximately 150 patients per treatment group.

Simron Singh, MD, MPH

The trial will be conducted in the United States and other countries, as applicable

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Primary Objective

• To assess superiority of treatment with CAM2029 compared to treatment with octreotide long-acting release (LAR) or lanreotide autogel (ATG) on progression-free survival (PFS) in patients with unresectable/metastatic and well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NET)

Primary Endpoint

• PFS, defined as the time from the date of randomization to the date of the first documented disease progression as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) or death due to any cause, whichever occurs first, as assessed by a Blinded Independent Review Committee (BIRC)

Secondary Objectives

• To assess superiority of treatment with CAM2029 compared to treatment with octreotide LAR or lanreotide ATG with respect to PFS based on local Investigator assessment
• To compare the 2 treatment groups with respect to overall survival
• To evaluate the 2 treatment groups with respect to overall response rate (ORR) and disease control rate (DCR)
• To describe time to tumor response and duration of response in the 2 treatment groups
• To evaluate the need for rescue medication for symptom control in the 2 treatment groups
• To assess the pharmacokinetics (PK) of octreotide after CAM2029 administration
• To assess octreotide exposure–response relationship for CAM2029
• To assess supervised self- or partner-administration of CAM2029
• To evaluate patient-reported outcomes (PROs) for health-related quality of life in the 2 treatment groups
• To evaluate the 2 treatment groups with respect to patient satisfaction with the treatment
• To confirm the safety and tolerability of CAM2029 in patients with unresectable/metastatic and well-differentiated GEP-NET

Secondary Endpoints

• PFS using RECIST 1.1 as assessed by local Investigators
• Overall survival
• ORR, defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) as per RECIST 1.1
• DCR, defined as the proportion of patients with best overall response of CR, PR or stable disease (SD) as per RECIST 1.1
• Time to response and duration of response as per RECIST 1.1
• Average number of injections of octreotide rescue medication per month for each patient during the trial
• Total dosage and dose intensity of rescue medication
• Octreotide plasma concentrations over time
• Correlation between octreotide concentration and other endpoints or measures as appropriate
• Proportion of patients/partners declared competent by trial personnel to administer CAM2029 out of those trying
• Change from baseline in Quality of Life Questionnaire – Neuroendocrine Carcinoid Module (QLQ-GINET21), Short Form-36 (SF-36), and the global health status/quality of life scale score of the European Organization for Research and Treatment of Cancer’s Core Quality of Life Questionnaire (EORTC QLQ-C30)
• Treatment Satisfaction Questionnaire for Medication (TSQM) scores over time using all 4 domains of TSQM (effectiveness, side effects, convenience, and global satisfaction)
• Adverse events (AEs) (including local tolerability)
• Changes in laboratory values, vital signs, electrocardiogram readings and gallbladder imaging

Exploratory Objectives

• To describe the effect of intensified treatment with CAM2029 in the Open-label Extension Treatment Period
• To compare the 2 treatment groups with respect to progression-free survival 2 (PFS2) based on local Investigator assessment
• To assess hospital resource utilization
• To evaluate the 2 treatment groups with respect to treatment experience
• To evaluate the 2 treatment groups with respect to patients’ impression of disease severity
• To evaluate the 2 treatment groups with respect to Eastern Cooperative Oncology Group (ECOG) performance status
• To assess the immunogenicity of octreotide in patients with metastatic/inoperable and well-differentiated GEP-NET

Exploratory Endpoints

• Progression-free survival in the Extension Treatment Period (PFS-ext), defined as time from date of randomization to the date of documented disease progression as per RECIST 1.1 or death from any cause, whichever occurs first, in the Open-label Extension Treatment Period, as assessed by a BIRC
• PFS2, defined as time from date of randomization to the date of documented progression as per RECIST 1.1 on next-line therapy or death from any cause, whichever occurs first
• Number of patients hospitalized
• Total number and length of hospitalizations
• Describe patients’ experiences with the trial regimen and trial activities using data from patient exit interviews
• Explore the minimal important difference for EORTC QLQ-C30 using patient exit interviews
• To explore the minimal important difference for EORTC QLQ-C30 using the Patient Global Impression of Severity (PGI-S) and patient exit interviews
• Time to deterioration of ECOG performance status
• Qualification and quantification of anti-octreotide antibodies

Main Inclusion Criteria for the Trial

• Male or female patient ≥18 years old
• Histologically confirmed, advanced (unresectable and/or metastatic), and well-differentiated NET of GEP or presumed GEP origin
• At least 1 measurable lesion according to RECIST 1.1 determined by multiphasic CT or MRI (performed within 28 days before randomization)
• Expression of somatostatin receptors on lesions documented by CT/MRI scans, assessed by somatostatin-receptor imaging modalities within 3 months before randomization
• Results from FDG-PET CT for patients with well-differentiated Grade 3 NET (if performed) must show that FDG avid areas of disease also are avid on somatostatin-receptor imaging
• ECOG performance status of 0 to 2

Main Inclusion Criteria for the Extension Treatment Period

• Disease progression confirmed by the BIRC
• At least 6 months of treatment with IMP (CAM2029/comparator) in the Randomized Treatment Period before documented disease progression

Main Exclusion Criteria for the Trial

• Documented evidence of disease progression while on treatment (including SSAs) for locally advanced unresectable or metastatic disease
• Known central nervous system metastases
• Consecutive treatment with long-acting SSAs for more than 6 months before randomization
• Carcinoid symptoms that are refractory to treatment (according to the Investigator’s judgement) with conventional doses of octreotide LAR or lanreotide ATG and/or to treatment with daily doses of ≤600 μg of octreotide IR
• Previous treatment with more than 1 cycle (where 1 cycle means ≤28 days on treatment) of targeted therapies such as mammalian target of rapamycin (mTOR) inhibitors (e.g. sirolimus, temsirolimus, or everolimus) or vascular endothelial growth factor inhibitors (e.g. sunitinib, lenvatinib, or cabozantinib), or more than 1 cycle of chemotherapy or interferon for GEP-NET
• Treatment of GEP-NET with trans-arterial chemoembolization or trans-arterial embolization within 12 months before screening
• Previously received radioligand therapy (peptide receptor radionuclide therapy) at any time
• Hepatic/pancreatic-related exclusion criteria:
  – Active hepatitis. Patients with no significant viral load, no acute signs of inflammation, and no clinical necessity for therapy are allowed, at the Investigator’s discretion
  – Known gallbladder or bile duct disease, or acute or chronic pancreatitis
  – Symptomatic cholelithiasis
  – Clinically active or chronic liver disease, including liver cirrhosis of Child-Pugh class B or C
• Patients with poorly controlled diabetes, as evidenced by hemoglobin A1c (HbA1c) >8.0%
• Cardiac history or current diagnosis of cardiac disease indicating significant risk of safety for patients participating in the trial, such as uncontrolled or significant cardiac disease, including any of the following:
  – History of myocardial infarction, unstable angina pectoris, or coronary artery bypass graft within 6 months before screening
  – Uncontrolled congestive heart failure
• Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, or high-grade atrioventricular block (e.g. bifascicular block, Mobitz type II, and third-degree atrioventricular block)
• Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
  – Risk factors for Torsades de Pointes, including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia
  – Treatment with concomitant medication(s) with a « known risk of Torsades de Pointes » per www.crediblemeds.org that cannot be discontinued or replaced with safe alternative medication at least 7 days or 5 half-lives (whichever is longer) before start of IMP treatment
  – Patients with a baseline QTc interval corrected by Fridericia’s formula >450 msec for males and >470 msec for females at screening
• Any other contraindicated serious medical condition that, in the Investigator’s opinion, may prevent the patient from safely participating in the trial

Main Exclusion Criteria for the Extension Treatment Period

• Unresolved, drug-related serious adverse event that, in the Investigator’s opinion, contraindicates treatment with CAM2029
• Clinically significant symptoms, medical conditions, rapid clinical deterioration, or other circumstances that, in the Investigator’s opinion, would preclude compliance with the protocol, adequate cooperation in the trial, or may prevent the patient from safely participating in the trial