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Poster Display session 1

3533 - First in human phase 1/2a study of PEN-866, a Heat Shock Protein 90 (HSP90) ligand – SN38 conjugate for patients with advanced solid tumors: Phase 1 results

Date

28 Sep 2019

Session

Poster Display session 1

Topics

Clinical Research

Tumour Site

Presenters

Johanna Bendell

Citation

Annals of Oncology (2019) 30 (suppl_5): v159-v193. 10.1093/annonc/mdz244

Authors

J.C. Bendell1, G. Falchook2, S. Sen2, M.L. Johnson3, G. Jerkovic4, N. Sarapa5, R. Vilimas6, K. Kriksciukaite7, L. Mei8, R. Wooster9, J. Bloss8, A. Thomas6

Author affiliations

  • 1 Drug Development Unit Nashville, Sarah Cannon Research Institute, 37203 - Nashville/US
  • 2 Drug Development Unit, Sarah Cannon Research Institute at HealthONE, 80218 - Denver/US
  • 3 Medical Oncology, Sarah Cannon Research Institute-Cancer Centre, 37203 - Nashville/US
  • 4 Pharmacovigilance, Sarah Cannon Development Innovations, 37203 - Nashville/US
  • 5 Medical /clinical Science, Sarah Cannon Development Innovations, 37203 - Nashville/US
  • 6 Developmental Therapeutics Branch, National Cancer Institute, 20892 - Bethesda/US
  • 7 Dmpk, Tarveda Therapeutics, Inc., 02472 - Watertown/US
  • 8 Clinical Development, Tarveda Therapeutics, Inc., 02472 - Watertown/US
  • 9 Discovery, Tarveda Therapeutics, Inc., 02472 - Watertown/US

Resources

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Abstract 3533

Background

HSP90 is a molecular chaperone that plays a key role in regulating the maturation and functional stability of a wide repertoire of cellular proteins, many of which play essential roles in tumorigenesis and is highly expressed in tumors. PEN-866, a miniature drug conjugate with an SN-38 payload that targets and binds to the activated tumor HSP90, yielded complete tumor regressions in multiple xenograft models. This study assessed the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of PEN-866.

Methods

Pts with progressive, advanced solid tumors were enrolled in escalating cohorts of 2-6 pts. The primary objective was to determine the maximum tolerated dose (MTD) of PEN-866 administered weekly for 3 of 4 weeks in a 28-day course. Preliminary efficacy was assessed using RECIST 1.1.

Results

21 pts with advanced solid tumors were treated in 7 cohorts (30-360 mg flat dosing or 175 – 200 mg/m2 BSA-based dosing). As of 30 Apr 2019, the median/mean number of cycles is 2/3.1 (range 1-15), with 5 pts ongoing. PEN-866 was well tolerated with no dose limiting toxicities (DLTs) in the first 4 cohorts (30-240 mg). In cohort 5 (360 mg), 1 of 3 pts had grade(G)3 diarrhea, a DLT that resolved with dose reduction. Two other pts experienced G3, uncomplicated neutropenia. In cohort 6 (175 mg/m2) 2 additional pts experienced G3 uncomplicated neutropenia. In cohort 7, 2 DLTs were observed (G5 dehydration and G3 fatigue). The MTD was determined to be 175 mg/m2. The most frequent (≥20% pts) PEN-866 related adverse events at data cut-off were nausea, diarrhea, fatigue, vomiting, alopecia, and neutropenia. PK was nonlinear, plasma exposures increased greater than dose proportionally and median t1/2 ∼7 h. Of 15 evaluable pts, 1 pt with squamous cell cancer of the anus had a partial response (-47%), 7 pts had stable disease (SD) at 8 wks, 4 were sustained for 12-57 wks, including 1 ongoing SD for 57 wks. Updated safety and efficacy data will be presented.

Conclusions

PEN-866 appears well tolerated with an expected adverse event profile and preliminary evidence of antitumor activity. PEN-866 will be evaluated in phase 2a expansion cohorts (NCT03221400).

Clinical trial identification

NCT03221400 July 18, 2017.

Editorial acknowledgement

Legal entity responsible for the study

Tarveda Therapeutics, Inc.

Funding

Tarveda Therapeutics, Inc.

Disclosure

J.C. Bendell: Research grant / Funding (institution): Tarveda Therapeutics; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Advisory/Consultancy to Institution: Gilead; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Advisory/Consultancy to Institution: Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Advisory/Consultancy to Institution: BMS; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Advisory/Consultancy to Institution: Lilly; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Advisory/Consultancy to Institution: Merck; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Advisory/Consultancy to Institution: MedImmune; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Advisory/Consultancy to Institution: Celgene; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Advisory/Consultancy to Institution: Taiho; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Advisory/Consultancy to Institution: Novartis; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Advisory/Consultancy to Institution: OncoMed; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Advisory/Consultancy to Institution: BI; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Advisory/Consultancy to Institution: ARMO; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Advisory/Consultancy to Institution: Ipsen; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Advisory/Consultancy to Institution: Oncogenex; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Advisory/Consultancy to Institution: FORMA; Advisory / Consultancy, Research grant / Funding (institution), Advisory/Consultancy to Institution: Five Prime; Advisory / Consultancy, Research grant / Funding (institution), Advisory/Consultancy to Institution: Macrogenics; Advisory / Consultancy, Research grant / Funding (institution), Advisory/Consultancy to Institution: GSK; Advisory / Consultancy, Research grant / Funding (institution), Advisory/Consultancy to Institution: LEAP; Advisory / Consultancy, Research grant / Funding (institution), Advisory/Consultancy to Institution: AstraZeneca; Research grant / Funding (institution): EMD Serono; Advisory / Consultancy, Research grant / Funding (institution), Advisory/Consultancy to Institution: TG Therapeutics; Advisory / Consultancy, Research grant / Funding (institution), Advisory/Consultancy to Institution: Daiichi Sankyo; Advisory / Consultancy, Research grant / Funding (institution), Advisory/Consultancy to Institution: Bayer; Advisory / Consultancy, Research grant / Funding (institution), Advisory/Consultancy to Institution: Incyte; Advisory / Consultancy, Research grant / Funding (institution), Advisory/Consultancy to Institution: Apexigen; Research grant / Funding (institution): Koltan; Research grant / Funding (institution): SynDevRex; Research grant / Funding (institution): Forty Seven; Research grant / Funding (institution): AbbVie; Advisory / Consultancy, Research grant / Funding (institution), Advisory/Consultancy to Institution: Array; Research grant / Funding (institution): Onyx; Advisory / Consultancy, Research grant / Funding (institution), Advisory/Consultancy to Institution: Sanofi; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Celldex; Advisory / Consultancy, Research grant / Funding (institution), Advisory/Consultancy to Institution: Agios; Research grant / Funding (institution): Cytomx; Research grant / Funding (institution): Nektar; Research grant / Funding (institution): Boston Biomedical; Advisory / Consultancy, Research grant / Funding (institution), Advisory/Consultancy to Institution: Merrimack; Research grant / Funding (institution): Tyrogenex; Research grant / Funding (institution): Marshall Edwards; Research grant / Funding (institution): Pieris; Research grant / Funding (institution): Mersana; Research grant / Funding (institution): Calithera; Research grant / Funding (institution): Blueprint; Research grant / Funding (institution): Evelo; Research grant / Funding (institution): Merus; Research grant / Funding (institution): Jacobio; Research grant / Funding (institution): Effector; Research grant / Funding (institution): Novocare; Research grant / Funding (institution): Arrys; Research grant / Funding (institution): Tracon; Research grant / Funding (institution): Sierra; Advisory / Consultancy, Research grant / Funding (institution), Advisory/Consultancy to Institution: Innate; Advisory / Consultancy, Research grant / Funding (institution), Advisory/Consultancy to Institution: Arch Oncology; Advisory / Consultancy, Research grant / Funding (institution), Advisory/Consultancy to Institution: Prelude Oncology; Research grant / Funding (institution): Unum Therapeutics; Research grant / Funding (institution): Vyriad; Research grant / Funding (institution): Harpoon; Research grant / Funding (institution): ADC; Advisory / Consultancy, Research grant / Funding (institution), Advisory/Consultancy to Institution: Amgen; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Millennium; Research grant / Funding (institution): Imclone; Research grant / Funding (institution): Acerta Pharma; Research grant / Funding (institution): Rgenix; Research grant / Funding (institution): Bellicum; Advisory / Consultancy, Advisory/Consultancy to Institution: Phoenix Bio; Advisory / Consultancy, Advisory/Consultancy to Institution: Cyteir; Advisory / Consultancy, Advisory/Consultancy to Institution: Molecular Partners; Advisory / Consultancy, Advisory/Consultancy to Institution: Torque; Advisory / Consultancy, Advisory/Consultancy to Institution: Tizona; Advisory / Consultancy, Advisory/Consultancy to Institution: Janssen; Advisory / Consultancy, Advisory/Consultancy to Institution: Tolero; Advisory / Consultancy, Advisory/Consultancy to Institution: Translational Drug Development; Advisory / Consultancy, Advisory/Consultancy to Institution: Seattle Genetics; Advisory / Consultancy, Advisory/Consultancy to Institution: Moderna Therapeutics; Advisory / Consultancy, Advisory/Consultancy to Institution: Tanabe Research Laboratories; Advisory / Consultancy, Advisory/Consultancy to Institution: BeiGene; Advisory / Consultancy, Advisory/Consultancy to Institution: Continuum Clinical; Advisory / Consultancy, Advisory/Consultancy to Institution: Kyn. G. Falchook: Research grant / Funding (institution): Tarveda Therapeutics, Inc; Licensing / Royalties: Wolters Kluwer; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: EMD Serono; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Advisory/Consultancy to institution: Fujifilm; Speaker Bureau / Expert testimony: Total Health Conferencing; Research grant / Funding (institution), Travel / Accommodation / Expenses: Millennium; Travel / Accommodation / Expenses: Bristol-Myers Squibb; Research grant / Funding (institution): Abbvie; Research grant / Funding (institution): ADC Therapeutics; Research grant / Funding (institution): 3-V Biosciences; Research grant / Funding (institution): Aileron; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): ARMO; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): BeiGene; Research grant / Funding (institution): Bioatla; Research grant / Funding (institution): Biothera; Research grant / Funding (institution): Celldex; Research grant / Funding (institution): Ciclomed; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): American Society of Clinical Oncology; Research grant / Funding (institution): Curegenix; Research grant / Funding (institution): Curis; Research grant / Funding (institution): DelMar; Research grant / Funding (institution): eFFECTOR; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Exelixis; Research grant / Funding (institution): Genmab; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Hutchison MediPharma; Research grant / Funding (institution): Ignyta; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Jacobio; Research grant / Funding (institution): Jounce; Research grant / Funding (institution): Kolltan; Research grant / Funding (institution): Loxo; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Merck; Research grant / Funding (institution): miRNA Therapeutics; Research grant / Funding (institution): National Institutes of Health; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): OncoMed; Research grant / Funding (institution): Oncothyreon; Research grant / Funding (institution): Precision Oncology; Research grant / Funding (institution): Regeneron; Research grant / Funding (institution): Rgenix; Research grant / Funding (institution): Strategia; Research grant / Funding (institution): Syndax; Research grant / Funding (institution): Taiho; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Tesaro; Research grant / Funding (institution): Tocagen; Research grant / Funding (institution): U.T. MD Anderson Cancer Center; Research grant / Funding (institution): Vegenics.S. Sen: Advisory / Consultancy, Advisory/Consultancy to Institution: Daiichi Sankyo; Research grant / Funding (institution): Bioatla; Research grant / Funding (institution): Exelixis; Research grant / Funding (institution): Fujifilm; Research grant / Funding (institution): Jacobio; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Loxo; Research grant / Funding (institution): SynthorX. M.L. Johnson: Research grant / Funding (institution): Tarveda Therapeutics, Inc; Research grant / Funding (institution), Travel / Accommodation / Expenses: Abbvie; Research grant / Funding (institution): BerGenBio; Research grant / Funding (institution): Lilly; Research grant / Funding (institution), Travel / Accommodation / Expenses: EMD Serono; Research grant / Funding (institution): Janssen; Advisory / Consultancy, Research grant / Funding (institution), Advisory/Consultancy to Institution: Mirati Therapeutics; Research grant / Funding (institution): Genmab; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Advisory/Consultancy to Institution: Pfizer; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Advisory/Consultancy to Institution: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Advisory/Consultancy to Institution: Genentech/Roche; Research grant / Funding (institution): Stemcentrix; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Checkpoint Therapeutics; Research grant / Funding (institution): Array BioPharma; Research grant / Funding (institution): Regeneron; Research grant / Funding (institution): Adaptimmune; Research grant / Funding (institution): Apexigen; Research grant / Funding (institution): Syndax; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Advisory/Consultancy to Institution: Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Advisory/Consultancy to Institution: Merck; Research grant / Funding (institution): Neovia; Advisory / Consultancy, Research grant / Funding (institution), Advisory/Consultancy to Institution: Sanofi; Research grant / Funding (institution): Hengrui Therapeutics, Inc; Research grant / Funding (institution), Travel / Accommodation / Expenses: Daiichi Sankyo; Research grant / Funding (institution): Lycera; Research grant / Funding (institution): G1 Therapeutics; Research grant / Funding (institution): Dynavax; Advisory / Consultancy, Research grant / Funding (institution), Advisory/Consultancy to Institution: LOXO; Research grant / Funding (institution): Cytomx; Advisory / Consultancy, Research grant / Funding (institution), Advisory/Consultancy to Institution: BeiGene; Research grant / Funding (institution): Birdie; Research grant / Funding (institution): Corvus; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Advisory/Consultancy to Institution: Incyte; Research grant / Funding (institution): Genocea; Research grant / Funding (institution): Gritstone; Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol Myers Squibb; Research grant / Funding (institution): Kadmon; Research grant / Funding (institution), Travel / Accommodation / Expenses: Clovis; Research grant / Funding (institution): Acerta; Research grant / Funding (institution): Oncomed; Advisory / Consultancy, Research grant / Funding (institution), Advisory/Consultancy to Institution: Guardant Health; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Shattuck Labs; Research grant / Funding (institution): GlaxoSmithKline; Travel / Accommodation / Expenses, Spouse / Financial dependant: Astellas; Spouse / Financial dependant: Otsuka Pharmaceuticals; Advisory / Consultancy, Advisory/Consultancy to Institution: Celgene; Advisory / Consultancy, Advisory/Consultancy to Institution: Calithera; Advisory / Consultancy, Advisory/Consultancy to Institution: Araxes Pharma; Advisory / Consultancy, Advisory/Consultancy to Institution: Mersana Therapeutics; Advisory / Consultancy, Advisory/Consultancy to Institution: Ribon Therapeutics; Travel / Accommodation / Expenses: Exelixis; Travel / Accommodation / Expenses: Sysmex Inostics; Travel / Accommodation / Expenses: Vapotherm. K. Kriksciukaite: Full / Part-time employment: Tarveda Therapeutics, Inc. L. Mei: Full / Part-time employment: Tarveda Therapeutics, Inc. R. Wooster: Shareholder / Stockholder / Stock options: Tarveda Therapeutics, Inc. J. Bloss: Full / Part-time employment: Tarveda Therapeutics, Inc. All other authors have declared no conflicts of interest.

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