Tarveda Therapeutics is discovering and developing a new class of potent and selective precision oncology medicines for the treatment of patients with various solid tumor malignancies. Their strategy includes developing their own proprietary Pentarin miniature conjugates to enhance the effectiveness of promising anti-cancer payloads that have struggled without their selective targeting to solid tumors. These medicines are known as ‘Pentarins’. PEN-221 is the lead candidate ‘Pentarin’ aimed at Neuroendocrine Cancer – PEN-221.
Somatostatin receptor 2 (SSTR2) is frequently overexpressed on several types of solid tumors, including neuroendocrine tumors and small-cell lung cancer. Peptide agonists of SSTR2 are rapidly internalized upon binding to the receptor and linking a toxic payload to an SSTR2 agonist is a potential method to kill SSTR2-expressing tumor cells. PEN-221 is a conjugate consisting of microtubule-targeting agent DM1 linked to the C-terminal side chain of Tyr3-octreotate. PEN-221 demonstrates in vitro activity which is both potent and receptor-dependent. PEN-221 targets high levels of DM1 to SSTR2-expressing xenograft tumors, which has led to tumor regressions in several SSTR2-expressing xenograft mouse models. The safety and efficacy of PEN-221 has been evaluated in human clinical trials (clinical trials information including Phase 1 data below).
The use of somatostatin analogues and somatostatin receptors to deliver the ‘payload’ would strongly indicate this is a targeted therapy.
The trial is aimed at all types of Neuroendocrine Neoplasms including well and poorly differentiated types, e.g. small cell and large cell lung Neuroendocrine Carcinoma, pheochromocytoma, paraganglioma, medullary thyroid carcinoma and merkel cell carcinoma. The use of somatostatin receptors is not new, this is currently the main route used by somatostatin analogues and also used in somatostatin receptor Theranostics (e.g. Ga68 PET an PRRT). However, Tarveda’s miniature drug conjugates are designed to maintain therapeutic properties while remaining miniature in size to enable rapid penetration into solid tumors. The plasma circulation time of hours is designed to allow for penetration into the tumor but to limit the overall exposure to normal tissue. Tarveda’s miniature drug conjugates are designed to accumulate anti-cancer payloads in the tumor by targeting and minimize effects on healthy tissue. The conjugates’ payloads are designed to remain masked while in circulation within the body to reduce normal tissue toxicity with unmasking occurring when the payload is cleaved in the tumor.
Protocol PEN-221 is an open-label, multicenter Phase 1/2 study evaluating PEN-221 in patients with SSTR2 expressing advanced gastroenteropancreatic (GEP) or lung or thymus or other neuroendocrine tumors or small cell lung cancer (SCLC) or large cell neuroendocrine carcinoma (LCNEC) of the lung. There’s also mention of Advanced paraganglioma, pheochromocytoma, medullary thyroid carcinoma, Merkel cell carcinoma, or high grade extrapulmonary neuroendocrine carcinoma having progressed after 1 or more lines of anticancer chemotherapy (unless no standard treatments available or such treatments are deemed not appropriate). The exclusion and inclusion criteria are extensive and those interested should read this section of the clinical trial document very carefully (see below). The phase 1 trial route of administration appears to be a one-hour IV infusion every 3 weeks.
The trial locations incudes several sites in US plus 4 locations in the UK.
Tarveda Therapeutics, Inc., a clinical stage biopharmaceutical company developing a new class of potent and selective precision oncology medicines, which it refers to as Pentarin® miniature drug conjugates, today announced that the company will present data from its Phase 2 clinical trial of PEN-221 at the 2021 American Society for Clinical Oncology (ASCO) Annual Meeting occurring virtually June 4-8, 2021.
PEN-221 is a miniature drug conjugate consisting of a peptide ligand that is highly selective in targeting the somatostatin receptor 2 (SSTR2), joined through a cleavable linker to the potent cytotoxic payload DM1. The Phase 2 trial assessed the safety, tolerability, pharmacokinetics, and preliminary efficacy of PEN-221 in well differentiated neuroendocrine tumors (NETs) and small cell lung cancer. The data being presented include safety and efficacy outcomes for patients enrolled in the gastrointestinal mid-gut NETs cohort.
“We are encouraged by the safety and efficacy results of our Phase 2 trial, which showed that PEN-221 was well tolerated and exceeded its clinical efficacy goals in patients with GI mid-gut neuroendocrine tumors,” said Brian Roberts, President and Chief Executive Officer of Tarveda. “We look forward to presenting the results of the study at this year’s ASCO Annual meeting and to further evaluating PEN-221 in GI mid-gut neuroendocrine tumors.”
Title: The safety and efficacy of PEN-221 somatostatin analog (SSA)-DM1 conjugate in patients (PTS) with advanced GI mid-gut neuroendocrine tumor (NET): Phase 2 results.
Abstract Number: 4110
Conclusions: PEN-221 appears well tolerated at 8.8 mg/m2 q 3 weeks and has demonstrated efficacy exceeding its clinical efficacy goals with a CBR of 88.5% and a mPFS of 9 months. A randomized trial of PEN-221 in GI mid-gut NET patients is now in development. Clinical trial information: NCT02936323
Further Reading:
1. Tarveda Therapeutics website – click here
2. The clinical trial document – click here
3. ASCO Poster with Phase 1 data – click here
4. ASCO Poster with Phase 2 data – click here
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided in the clinical trials document. It’s very important to check the trial inclusion and exclusion criteria before making any contact. If you need questions, the articles here is very useful Questions to Ask About Clinical Trials | Cancer.Net
The inclusion of any trial within this blog should not be taken as a recommendation by Ronny Allan.
Thanks for reading.
Blog Facebook. Like this page please.
Personal Facebook. Like this page please.
Awareness Facebook Like this page please.
Follow me on X (formerly twitter)
Check out my online presentations
Check out my WEGO Health Awards
My diagnosis came with many strange words including, “carcinoid” and “neuroendocrine” ……… can you spell that please, I said to the doctor. I had a
Ronny Allan’s ‘PoNETry’ © series can be shared with poetry credit to: RonnyAllan.NET Thanks for reading Ronny I also have one about Lanreotide (or “butt
When I was diagnosed, I didn’t even feel ill. It was therefore a bit of a shock being told I had metastatic cancer, advanced enough to
I was assessing performance of the awareness period in November 2025 on Facebook and was astonished to find the size of my reach on that
Here is the monthly summary of November 2025 on RonnyAllan.NET – Every share helps someone understand or even work towards a diagnosis, discovery of the
Discover more from Ronny Allan – Living with Neuroendocrine Cancer Subscribe to get the latest posts sent to your email. Type your email… Subscribe
Bone metastases in Neuroendocrine Tumours (NET) Many of you will know that I am a stage IV small intestine NET and I have one bone
What is Radioligand Therapy? When you browse the internet, you may see the term “Radioligand Therapy (RLT)” and wondered what it was. There’s a simple
D Day I was 54 years and 9 months old at diagnosis on 26th July 2010. For the first few months, I had no idea
Subscribe to get the latest posts sent to your email.
