Tarveda Therapeutics Reports Complete Data from Phase 1 Portion of Phase 1/2a Study of PEN-866 to be Presented at the ASCO20 Virtual Scientific Program

May 13, 2020 Off By BusinessWire

PEN-866 demonstrates a favorable therapeutic index with a broad therapeutic range, was well tolerated and showed evidence of anti-tumor activity in patients with advanced solid tumor malignancies

Pharmacokinetic data show that PEN-866 is concentrated and retained in tumor where it slowly releases its toxic payload in the tumor while being efficiently cleared intact from plasma

WATERTOWN, Ma.–(BUSINESS WIRE)–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 the complete data from the Phase 1 dose escalation portion of a Phase 1/2a study of PEN-866 in advanced solid tumor malignancies. PEN-866 was well-tolerated, demonstrated a high therapeutic index, and showed evidence of anti-tumor activity across multiple tumors and dose ranges (wide therapeutic range), including one partial response. The data also confirm the favorable pharmacokinetic profile of PEN-866 and its ability to engage with its intended target and concentrate delivery of its toxic SN-38 payload intra-tumorally.

The full results of the Phase 1 portion of the Phase 1/2a study will be presented at the American Society for Clinical Oncology’s ASCO20 Virtual Scientific Program in a presentation titled, “PEN-866, a Miniature Drug Conjugate of a Heat Shock Protein 90 (HSP90) Ligand Linked to SN38 for Patients with Advanced Solid Malignancies: Phase 1 and Expansion Cohort Results”. Along with the Sarah Cannon Research Institute, the National Cancer Institute (NCI) at the National Institutes of Health (NIH), Stephenson Cancer Center at the University of Oklahoma, and Tennessee Oncology are also participating as trial sites. NCI investigators, Drs. Anish Thomas, MBBS, M.D., and Yves Pommier, M.D., Ph.D., Developmental Therapeutics Branch, Center for Cancer Research, NCI, are collaborating with Tarveda through a clinical Cooperative Research and Development Agreement (CRADA).

“The full data from the Phase 1 portion of the PEN-866 Phase 1/2a study show that through binding to HSP90, which is upregulated and activated in solid tumors, PEN-866 accumulates and is retained in solid tumors where it releases its toxic payload, as designed,” said Gerald Falchook, Sarah Cannon Research Institute. “PEN-866 was well tolerated and demonstrated a strong therapeutic index across multiple tumor types. We were also highly encouraged by the anti-tumor activity in this advanced patient population, including several patients experiencing prolonged stable disease and one experiencing a partial response.”

“The results seen from the Phase 1 study of PEN-866 show the potential not just of PEN-866 itself but of Tarveda’s HSP90 binding miniature drug conjugate platform,” said Jeffrey Bloss, M.D., Chief Medical Officer of Tarveda. “Results from this trial confirm that PEN-866 works as designed and successfully concentrated its potent SN-38 anti-tumor payload in the tumor. We will be progressing with further evaluations of PEN-866 both as a monotherapy in patients with a range of solid tumor malignancies in a Phase 2a trial, as well as in combination with cytotoxic chemotherapy and other targeted agents such as DDR, immuno-oncology drugs and key pathway inhibitors. We are also building out our HSP90 binding miniature drug conjugate platform by exploring and developing new HSP90 binding miniature drug conjugates with promising anti-cancer payloads.”

PEN-866 is an HSP90 binding miniature drug conjugate that preferentially binds to activated HSP90 in solid tumors and is linked to the topoisomerase 1 inhibitor SN-38, a potent anti-cancer payload. PEN-866 is designed to accumulate and be retained in solid tumors while clearing rapidly from plasma intact over 24 to 48 hours. As the SN-38 payload is cleaved in the tumor over time, the sustained release of SN-38 in the tumor results in prolonged DNA damage and tumor regressions as demonstrated in multiple patient-derived and cancer cell line xenograft models. PEN-866 is the first miniature drug conjugate from Tarveda’s HSP90 binding drug conjugate platform.

Phase 1 Trial Design

In this dose escalating Phase 1 portion of the trial, 30 patients were enrolled in seven dose levels. Two to seven patients with advanced solid tumor malignancies were treated in each cohort. Patients received escalating doses of PEN-866 weekly for three out of four weeks in a 28-day cycle. Patients in cohorts 1-5 were treated with flat dosing and patients in cohorts 6-7 were switched to body surface area dosing based on emerging data indicating variable exposure in patients treated with flat doses.

Safety Data

Results of the study show that PEN-866 was well tolerated with no dose limiting toxicities (DLTs) in the first six cohorts (15 mg/m2 – 175 mg/m2). Three DLTs were observed above the Maximum Tolerated Dose (MTD) which was 175 mg/m2. One fatal event of dehydration occurred 11 days following the last dose of PEN-866 at the dose level above the MTD. The most frequent adverse events observed were nausea, fatigue, diarrhea, vomiting, and alopecia and the most common Grade 3 adverse event was neutropenia. The neutropenia seen at the MTD or below was uncomplicated, did not require growth factors for patients to recover, and did not result in missed or delayed doses. The recommended Phase 2 dose for PEN-866 monotherapy was determined to be 175 mg/m2.

Efficacy Data

Antitumor activity was observed across multiple tumor types and at a wide range of doses. One patient (3.8%) of 26 evaluable patients per RECIST v1.1 achieved partial response (PR) and 11 patients (42.3%) experienced stable disease (SD). Patients who experienced clinical benefit include:

  • One patient with anal squamous carcinoma had a PR, approximately a 50% reduction in tumor size within four cycles (duration of response > 11 months)
  • Three patients with pancreatic cancer had prolonged SD (8 months, 5 months and 4.5 months, respectively)
  • One patient with liposarcoma had prolonged SD (>12 months)
  • One patient with acinar cell cancer of the pancreas remained on therapy for over a year with SD

ASCO20 Virtual Scientific Program Presentation

Full results of the study will be presented at the ASCO20 Virtual Scientific Program. Details of the poster presentation are as follows:

Title: PEN-866, a Miniature Drug Conjugate of a Heat Shock Protein 90 (HSP90) Ligand Linked to SN-38 for Patients with Advanced Solid Malignancies: Phase 1 and Expansion Cohort Results

Date: Friday, May 29, 2020

Time: 8:00 AM ET

Location: ASCO20 Virtual Scientific Program accessible at https://meetings.asco.org/am/virtual-format

Additional information on the Phase 1/2a clinical trial for PEN-866 is available at clinicaltrials.gov, through identifier number NCT03221400.

About Tarveda Therapeutics®, Inc.

Tarveda Therapeutics is 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, for the treatment of patients with various solid tumor malignancies. Tarveda’s Pentarin® miniature drug conjugates are designed to take the best properties of both small molecule drugs and antibody drug conjugates to form a miniature drug conjugate able to penetrate into solid tumors, selectively bind to the desired tumor targets and accumulate the anti-cancer payloads directly in tumor cells. The anti-cancer payload is retained in tumor and then released over time causing the anti-cancer payload to become active in the tumor.

Tarveda currently has two Pentarin® miniature drug conjugates in clinical trials. Its first clinical program, PEN-866, is the initial candidate from Tarveda’s HSP90 binding miniature drug conjugate platform. HSP90 is a molecular chaperone that is highly activated in the harsh tumor environment across a wide range of solid tumor cancers, but which remains relatively dormant in normal tissue. Tarveda’s binding moieties of its HSP90 binding miniature drug conjugates have been shown to bind with high affinity to HSP90, which is frequently activated and overexpressed in solid tumor cells. PEN-866 has completed its Phase 1 dose escalation portion of its “all comers” trial in various types of solid tumors. In addition to PEN-866, Tarveda is developing additional miniature drug conjugates on its HSP90 binding miniature drug conjugate platform to target other promising anti-cancer payloads such as kinase inhibitors and radioisotopes to solid tumors. Tarveda’s second clinical program, PEN-221, is a Pentarin® miniature drug conjugate currently in clinical evaluation for the treatment of patients with solid tumors expressing SSTR2 on the cell surface as is seen in neuroendocrine tumors and small cell lung cancer. PEN-221 is currently progressing through its Phase 2a trial. For more information regarding Tarveda, go to: http://www.tarvedatx.com.

Contacts

Amanda Houlihan

MacDougall

781 235 3060

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