Phase 1/2a to asses PEN-221 in receptor 2 expressing advanced cancers
Research type
Research Study
Full title
A Phase 1/2a, open-label multicenter study to assess the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of PEN-221 in patients with somatostatin receptor 2 expressing advanced cancers, including gastroenteropancreatic or lung or thymus or other neuroendocrine tumors or small cell lung cancer or large cell neuroendocrine carcinoma of the lung
IRAS ID
210606
Contact name
Timothy Meyer
Contact email
Sponsor organisation
Tarveda Therapeutics, Inc.
Eudract number
2016-001468-12
Duration of Study in the UK
2 years, 0 months, 18 days
Research summary
Research Summary
The present study is a Phase 1/2a multicentre, open label, First in Human, dose-escalating safety study of PEN-221 in patients with somatostatin receptor 2 expressing advanced cancers.
The purpose of this research study is to establish the safety profile of the medication in patients with advanced cancers.
The study drug PEN-221 might be able to bind to a kind of cancer cell that contains a high amount of a molecule called somatostatin receptor and then might be able to stop those cancer cells from growing.
The patient population in the Dose Escalation part will be patients with advanced cancers who have failed available standard treatments or are not candidates for standard therapy.
The study consists of three parts: Phase 1a, a Dose Escalation part, Phase 1b, an Early Expansion where patients will be enrolled based on the data obtained from the Dose Escalation part and Phase 2a, in which a patients may begin at the discretion of the Sponsor, once all patients treated in Phase 1 Part B have been assessed for safety, and the Safety Review Committee has reviewed all safety data and recommends continuing with Phase 2a.
The study will be conducted in 2 sites in the United Kingdom and 4 sites in the United States. Patients may be expected to participate in the study for up to 2 years.Summary of Results
This study is officially known as a phase 1/2a, open-label multicenter study to assess the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of PEN-221 in patients with somatostatin receptor 2 expressing advanced cancers, including gastroenteropancreatic or lung or thymus or other neuroendocrine tumors or small cell lung cancer or large cell neuroendocrine carcinoma of the lung Why the Study was Done The purpose of this study was to learn how PEN-221 affected the body and how the body affected PEN-221. The study looked at how well patients with advanced cancer tolerated PEN-221. The study also looked for the most useful dose of PEN-221, learned how the amount of PEN-221 changes over time in blood, and looked at whether PEN-221 may make tumors get smaller or disappear. This study included only patients with a cancer cell that contained a high amount of a molecule called somatostatin receptor which helps to control other hormones in the body. This study included a Phase 1 portion and a Phase 2a portion and patients were allowed to participate in the study only if they met criteria listed in the study Protocol.
Trial Summary
This study started in December 2016 and ended in February 2021. A total of 89 patients participated in the Phase 1/2a study from the United Kingdom and the United States.
Phase 1
The Phase 1 portion of the study was a dose escalation study which means small numbers of patients identified with somatostatin receptor 2 expressing advanced gastroenteropancreatic or lung or thymus or other neuroendocrine tumors or small cell lung cancer or large cell neuroendocrine carcinoma of the lung were given different doses of PEN-221. Each dose group who entered the study was given a slightly higher dose of only PEN-221 than the group before based on the decision of a group of experts called a Safety Review Committee (SRC). The reason for doing the dose escalation portion of the study was to find the highest dose of PEN-221 without having severe side effects.
There was a total of 23 patients who participated in the Phase 1 portion of the study with a total of 7 groups of patients, each receiving a slightly higher dose than the group before of PEN-221 administered intravenously (IV) once on an every 3 week schedule. The first group had 2 patients dosed at 1 mg each, groups 2-5 had 3 patients in each group with doses at 2 mg, 4 mg, 8 mg, and 12 mg respectively, group 6 had 6 patients dosed at 18 mg, and group 7 had 3 patients dosed at 25 mg PEN-221. Of the 3 patients in group 7 dosed at 25 mg PEN-221, 2 of the 3 patients experienced a Dose Limiting Toxicity (DLT), which was defined as any Grade 3 (Severe) or Grade 4 (Life-Threatening or disabling) adverse event (AE) using the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 occurring within the first 4 weeks for the first group and within 3 weeks for each subsequent group that was not related to underlying disease, disease progression, intercurrent illness, or concomitant medications. The Primary results of the Phase 1 portion of the study showed that 18 mg flat dose of PEN-221 administered IV once every 3 weeks as the maximum tolerated dose and established the Phase 2a recommended dose at the flat dose of 18 mg of PEN-221.
This was the first time PEN-221 was studied in humans and this treatment was evaluated for side effects. The safety results of the Phase 1 portion of the study showed PEN-221 having an acceptable safety and tolerability profile at 18 mg flat dose administered IV once every 3 weeks.
Phase 2a
There was a total of 66 patients who participated in the Phase 2a portion of the study who were allocated to one of three groups based on evidence of having a somatostatin receptor 2 expressing advanced or metastatic, well differentiated, low or intermediate grade gastrointestinal neuroendocrine tumor (GINET – 32 patients) or pancreatic neuroendocrine tumor (PNET – 15 patients), or advanced or metastatic small cell lung cancer (SCLC – 19 patients). Patients participating in the Phase 2a portion of the study did not participate in Phase 1.
The patients participating in the Phase 2a portion of the study received PEN-221 at the Phase 2a recommended starting dose of 18 mg flat dose IV once every 3 weeks. After review of 19 Phase 2a patients, the SRC decreased the start dose from 18 mg to 15 mg flat dose due to higher-than-expected treatment discontinuation rate. After review of all Phase 1 and 31 Phase 2a patients, the SRC changed 15 mg flat dose to Body Surface Area (BSA) based PEN-221 dose of 8.8 mg/m^2 due to a correlation between BSA and drug exposure (AUC) associated with higher rate of patients discontinuation.
Results from the Phase 2a portion of the study were analyzed by cancer type. For the GINET group, the protocol defined objective of Clinical Benefit Rate (CBR), defined as the best overall response of complete response (CR), partial response (PR), or stable disease (SD) according to RECIST 1.1 using the investigator assessment, was met with 23 of 26 evaluable patients (88.5%) having Stable Disease (SD) as a Best Response (BR) and 13 (50%) patients having tumor shrinkage as a Best Response. Progression Free Survival (PFS), defined as the time from the date of first dose of PEN-221 to the date of first documented disease progression per RECIST 1.1, or death due to any cause, was also met in the GINET group with a median PFS of 9 months. The protocol defined efficacy objectives of Clinical Benefit Rate (CBR) and Progression Free Survival (PFS) were not met in the PNET group. PEN-221 did not demonstrate the protocol defined efficacy objectives of Objective Response Rate in patients with SCLC.
The safety results of PEN-221 in the Phase 2a portion of the study was shown to have an acceptable safety and tolerability profile at 8.8 mg/m^2 BSA based dose administered IV once every 3 weeks.
Study Sponsor
This study was sponsored by Tarveda Therapeutics, Inc. If you have any questions, please contact Tarveda Clinical Information at clinical.information@tarvedatx.com.
This summary was completed in March 2022. This summary includes only results from one single study from information collected from December 2016 through July 2020. There are no other studies conducted of PEN-221. There are no other PEN-221 studies planned.REC name
London - Central Research Ethics Committee
REC reference
16/LO/1641
Date of REC Opinion
9 Nov 2016
REC opinion
Further Information Favourable Opinion