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

Protocol PEN-221-001 is an open-label, multicenter Phase 1/2a 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 or large cell neuroendocrine carcinoma of the lung.

Start Date08 Dec 2016

Sponsor / Collaborator

Tarveda Therapeutics, Inc.

100 Clinical Results associated with PEN-221

100 Translational Medicine associated with PEN-221

100 Patents (Medical) associated with PEN-221

Literatures (Medical) associated with PEN-221

01 Dec 2023·Advanced Healthcare Materials

Phenylboronic Acid‐Modified Near‐Infrared Region II Excitation Donor–Acceptor–Donor Molecule for 2‐Deoxy‐d‐Glucose Improved Starvation/Chemo/Photothermal Combination Therapy

Article

Author: He, Jiarong ; Li, Daifeng ; He, Liuliang ; Fan, Quli ; Shen, Qingming ; Xu, Wenjuan ; Chen, Pengfei ; Yang, Wan ; Sun, Pengfei

AbstractSynergistic chemotherapy and photothermal therapy (PTT) have emerged as a promising anticancer paradigm to achieve expected therapeutic effects while mitigating side effects. However, the chemo/PTT combination therapy suffers from limited penetration depth, thermoresistance performance of tumor cells, and low drug bioavailability. Herein, multifunctional nanoparticles (BTP/DOX/2DG NPs) coloaded with near‐infrared region II (NIR‐II) light excitation donor–acceptor–donor (D–A–D) small molecules, doxorubicin (DOX), and 2‐deoxy‐d‐glucose (2‐DG) are developed for reinforced starvation/chemo/NIR‐II PTT combination therapy. The synthesized phenylboronic acid (PBA)‐modified water‐soluble D–A–D molecule (BBT‐TF‐PBA) not only exhibits high binding ability to DOX and 2‐DG through donor–acceptor coordination interactions PBA–diol bonds but also serves as a photoactive agent for NIR‐II fluorescence imaging, NIR‐II photoacoustic imaging, and NIR‐II PTT. Under the acidic and oxidizing conditions in the tumor microenvironment, donor–acceptor coordination interactions and PBA–diol bond are decomposed, simultaneously releasing DOX and 2‐DG from BTP/DOX/2DG NPs to achieve effective chemotherapy and starvation therapy. 2‐DG also effectively inhibits the expression of heat shock protein and further enhances NIR‐II PTT and chemotherapy efficiency. In vitro and in vivo experiments demonstrate the combination effect of BTP/DOX/2DG NPs for chemotherapy, NIR‐II PTT, and starvation therapy.

01 Nov 2019·Molecular Cancer TherapeuticsQ2 · MEDICINE

Targeting the Somatostatin Receptor 2 with the Miniaturized Drug Conjugate, PEN-221: A Potent and Novel Therapeutic for the Treatment of Small Cell Lung Cancer

Q2 · MEDICINE

Article

Author: DuPont, Michelle M. ; Alargova, Rossitza ; Brockman, Adam ; Sweryda-Krawiec, Beata ; Bilodeau, Mark T. ; Kriksciukaite, Kristina ; Shinde, Rajesh ; Whalen, Kerry A. ; Lemelin, Charles-Andre ; Moreau, Benoît ; Quinn, James M. ; Perino, Samantha ; Au Yeung, Tsun P. ; Bazinet, Patrick ; Wooster, Richard ; Gifford, James ; Sharma, Gitanjali ; White, Brian H. ; Oller, Haley ; Lim Soo, Patrick

AbstractSmall cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma with a 95% mortality rate with no improvement to treatment in decades, and new therapies are desperately needed. PEN-221 is a miniaturized peptide–drug conjugate (∼2 kDa) designed to target SCLC via a Somatostatin Receptor 2 (SSTR2)–targeting ligand and to overcome the high proliferation rate characteristic of this disease by using the potent cytotoxic payload, DM1. SSTR2 is an ideal target for a drug conjugate, as it is overexpressed in SCLC with limited normal tissue expression. In vitro, PEN-221 treatment of SSTR2-positive cells resulted in PEN-221 internalization and receptor-dependent inhibition of cellular proliferation. In vivo, PEN-221 exhibited rapid accumulation in SSTR2-positive SCLC xenograft tumors with quick clearance from plasma. Tumor accumulation was sustained, resulting in durable pharmacodynamic changes throughout the tumor, as evidenced by increases in the mitotic marker of G2–M arrest, phosphohistone H3, and increases in the apoptotic marker, cleaved caspase-3. PEN-221 treatment resulted in significant antitumor activity, including complete regressions in SSTR2-positive SCLC xenograft mouse models. Treatment was effective using a variety of dosing schedules and at doses below the MTD, suggesting flexibility of dosing schedule and potential for a large therapeutic window in the clinic. The unique attributes of the miniaturized drug conjugate allowed for deep tumor penetration and limited plasma exposure that may enable long-term dosing, resulting in durable tumor control. Collectively, these data suggest potential for antitumor activity of PEN-221 in patients with SSTR2-positive SCLC.

14 Mar 2019·Journal of Medicinal ChemistryQ1 · MEDICINE

Discovery of an SSTR2-Targeting Maytansinoid Conjugate (PEN-221) with Potent Activity in Vitro and in Vivo

Q1 · MEDICINE

Article

Author: Sharma, Gitanjali ; Lim Soo, Patrick ; Kriksciukaite, Kristina ; Oller, Haley ; Bilodeau, Mark T. ; Perino, Samantha ; Moreau, Benoît ; Quinn, James M. ; Lemelin, Charles-Andre ; White, Brian H. ; Whalen, Kerry ; Alargova, Rossitza ; Bazinet, Patrick ; Wooster, Richard ; DuPont, Michelle ; Sweryda-Krawiec, Beata ; Au Yeung, Tsun ; Shinde, Rajesh ; Brockman, Adam

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. Herein, we describe our efforts towards an efficacious SSTR2-targeting cytotoxic conjugate; examination of different SSTR2-targeting ligands, conjugation sites, and payloads led to the discovery of 22 (PEN-221), 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 (IC₅₀ = 10 nM) and receptor-dependent (IC₅₀ shifts 90-fold upon receptor blockade). 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 is currently under evaluation in human clinical trials.

100 Deals associated with PEN-221

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced cancer	Phase 2	US	Tarveda Therapeutics, Inc.	08 Dec 2016
Advanced cancer	Phase 2	GB	Tarveda Therapeutics, Inc.	08 Dec 2016
Neuroendocrine Carcinoma	Phase 2	US	Tarveda Therapeutics, Inc.	08 Dec 2016
Neuroendocrine Carcinoma	Phase 2	GB	Tarveda Therapeutics, Inc.	08 Dec 2016
Small Cell Lung Cancer	Phase 2	GB	Tarveda Therapeutics, Inc.	08 Dec 2016
Small Cell Lung Cancer	Phase 2	US	Tarveda Therapeutics, Inc.	08 Dec 2016
undifferentiated large cell lung cancer	Phase 2	GB	Tarveda Therapeutics, Inc.	08 Dec 2016
undifferentiated large cell lung cancer	Phase 2	US	Tarveda Therapeutics, Inc.	08 Dec 2016

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