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PEN-866 in Patients With Advanced Solid Malignancies

Trial Status: Active

Protocol PEN-866-001 is an open-label, multi-center, first-in-human Phase 1 / 2a study evaluating PEN-866 in patients with advanced solid malignancies whose disease has progressed after treatment with previous anticancer therapies.

Inclusion Criteria

  • M/F at least 18 years old
  • Performance status 0 or 1
  • Adequate bone marrow, liver, and kidney function within 28 days prior to first dose
  • Serum potassium, calcium, magnesium, phosphorus within normal limits
  • Adequate birth control
  • Central venous access line is required
  • Patients in Phase 1a and Phase 1b must also have confirmed advanced solid malignancy that has progressed after one or more prior lines of anticancer therapy and no other standard of care therapies that are deemed appropriate for treatment of their malignancy
  • Patients in Phase 2a must have measurable disease per RECIST 1.1 and documented disease progression during or after their most recent line of anticancer therapy.
  • Patients in Phase 2a must have disease history specific to their disease as listed below:
  • Small Cell Lung Cancer (SCLC): Patients with locally recurrent or metastatic SCLC whose disease has progressed after having received one or more prior lines of chemotherapy.
  • Gastric or gastroesophageal (GEJ) adenocarcinoma: Patients with locally recurrent or metastatic gastric or GEJ adenocarcinoma whose disease has progressed after having received one or more prior lines of chemotherapy.
  • Squamous cell carcinoma (SCC) of the genitalia (anus, cervix, vulva, or penis): Patients with locally recurrent or metastatic SCC of the genitalia (anus, cervix, vulva, or penis) whose disease has progressed after having received one or more prior lines of chemotherapy, including those whose disease has progressed after postoperative adjuvant chemotherapy or neoadjuvant chemotherapy prior to radiation or surgery.
  • Pancreatic adenocarcinoma (PDAC): Patients with locally recurrent or metastatic PDAC whose disease has progressed after having received one or more prior lines of chemotherapy, including those whose disease has progressed within 6 months of postoperative adjuvant chemotherapy.
  • Endometrial adenocarcinoma (EC): Patients with locally recurrent or metastatic EC whose disease has progressed after having received one or more prior lines of chemotherapy, including those whose disease has progressed within 6 months of postoperative adjuvant chemotherapy.
  • For Phase 1b patients only: Patients with metastatic PDAC who have progressed after having received one or more prior lines of chemotherapy, including those whose disease has progressed within 6 months of postoperative adjuvant chemotherapy.

Exclusion Criteria

  • Treatment with anticancer therapy or investigational drug or device within 2 wk (6 wk for nitrosureas or mitomycin C) before C1D1, and any drug-related toxicities must have recovered to grade 1 or less with the exception of alopecia and peripheral neuropathy.
  • Phase 2a only: Prior treatment with topoisomerase I inhibitor(s).
  • Cardiac disease such as unstable angina within 6 months of screening, myocardial infarction within 6 months of screening, NY Heart Association Class III - IV heart failure, QTc greater than 470 msec, congenital long Qt syndrome, symptomatic orthostatic hypotension within 6 months of screening, uncontrolled hypertension, or clinically important abnormalities in heart rhythm, conduction, morphology of resting ECG
  • Stroke or transient ischemic attack within 6 months of screening
  • Peripheral neuropathy greater than grade 2
  • Patients requiring medications with drugs that are inhibitors of UGT1A1 or substrates of CYP1A2, P-gP, BCRP, OATP1B1, OATP1B3 or OCT1 transporters
  • History of leptomeningeal disease or spinal cord compression
  • Brain metastases unless asymptomatic. Stable low dose of steroids is permitted.
  • As judge by the Investigator major surgery within 28 days of first drug dose
  • Female pregnant or breast feeding
  • Evidence of severe uncontrolled systemic disease, bleeding diatheses, renal or liver transplant, active infection with hep B or C or HIV
  • Hypersensitivity or anaphylactic reaction to ganetespib or other HSP90 inhibitors, irinotecan, SN-38 or its derivatives
  • Any medical, psychological, or social condition that would interfere with the patient's participation in the study.

Oklahoma

Oklahoma City
University of Oklahoma Health Sciences Center
Status: ACTIVE

Phase 1a will employ an adaptive model guided with overdose control principle to make dose

recommendations and estimate the maximum tolerated dose (MTD) of PEN-866 (single agent).

Phase 1b will employ a standard 3 + 3 design to make dose recommendations and estimate the

MTD of combination therapy in patients with pancreatic adenocarcinoma (PDAC).

Phase 2a (single agent) begins once all patients treated in Phase 1a have been assessed for

safety and the Safety Review Committee (SRC) has reviewed all safety data and recommends

continuing with Phase 2a. PEN-866 will be evaluated using the recommended Phase 2 dose

identified by the SRC at the conclusion of Phase 1a (single agent) based on the safety,

tolerability, pharmacokinetic, and pharmacodynamics profile of PEN-866 (single agent)during

Phase 1a.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
Tarveda Therapeutics

  • Primary ID PEN-866-001
  • Secondary IDs NCI-2020-01132
  • Clinicaltrials.gov ID NCT03221400