Dose Escalation, First-in-human Clinical Trial to Evaluate the Safety, Pharmacokinetics and Preliminary Antitumor Activity of PEP-010, Administered as Single Agent and in Combination With Paclitaxel in Patients With Metastatic Solid Cancer

  • STATUS
    Recruiting
  • End date
    Dec 31, 2023
  • participants needed
    56
  • sponsor
    Institut Curie
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Updated on 28 October 2022
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Summary

This is an open-label, non-controlled, multicenter, dose escalation, first-in-human phase I clinical trial with an expansion phase designed to assess the safety, tolerability, PK and PD parameters, and preliminary antitumor activity of intravenous dosing of PEP-010 as single agent and in combination with paclitaxel.

PEP-010 will be administered as single agent in patients with solid cancers who are not amenable to standard treatment, or in combination in patients who are eligible for the paclitaxel therapy.

Description

PEP-010 will be administered on days 1, 2 and 3 every week. Treatment will be administered until disease progression, unacceptable toxicity, death or withdrawal of consent, whichever occurs first. Each cycle will be of 21 days duration.

The initial starting dose of PEP-010, DL1 is selected based on pre-clinical data at 0.15 mg/kg. The other doses per injection from DL2 to DL7 are 0.3, 0.6; 1.2; 2.5; 5; 10 and 15 mg/kg.

For patients in Arm B, PEP-010 will be combined with Paclitaxel, at a dose of 80 mg/m², weekly until disease progression or unacceptable toxicity. Paclitaxel will be administered according to local guidelines.

Main objective for Dose escalation cohorts is to determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of PEP-010 when administered as single agent (MTD1/RP2D1), and in combination with paclitaxel (MTD2/RP2D2) by recording the dose-limiting toxicities (DLTs).

Main objective for Expansion cohorts is to confirm the RP2Ds of PEP-010 as a single agent and/or in combination in patients with metastatic and/or recurrent cancer.

Secondary objectives are

  • To evaluate the safety and tolerability of PEP-010 when administered as single agent, and in combination with paclitaxel.
  • To assess the pharmacokinetics (PK) of PEP-010 as single agent, and in combination with paclitaxel in Dose escalation cohorts.
  • To assess the pharmacodynamic (PD) effects of PEP-010 as single agent, and in combination with paclitaxel.
  • To evaluate the preliminary antitumor activity of PEP-010 alone and in combination with paclitaxel, using Objective Response Rate (ORR), Progression-Free Survival (PFS) according to RECIST1.1, duration of response, and Overall Survival (OS).
  • To assess the immunogenicity of PEP-010 as single agent, and in combination with paclitaxel in Dose escalation cohorts.

Details
Condition Metastatic Solid Tumor Cancer
Treatment Dose escalation, first-in-human phase I clinical trial with an Expansion phase
Clinical Study IdentifierNCT04733027
SponsorInstitut Curie
Last Modified on28 October 2022

Eligibility

 Yes No Not Sure

Inclusion Criteria

Part I and II, Arms A and B
Arm A: Patients must have histologically confirmed diagnosis of recurrent and/or metastatic solid tumors, who are not amenable to standard therapy, with exceptions as defined in the non-inclusion criteria
Arm B: Patients must have histologically confirmed diagnosis of recurrent and/or metastatic solid tumors. Patients must be eligible for a treatment with paclitaxel as single agent. Patients who are eligible for standard of care paclitaxel-based combination therapy should not be included in the trial, unless they have been previously exposed to that specific combination therapy. Specifically
Patients with ovarian cancer must have received prior therapy with paclitaxel as part of standard of care in combination with carboplatin
Patients with triple negative breast cancer are eligible for the trial since paclitaxel as single agent is standard of care in this disease
Age ≥ 18 years
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1
Patients must have measurable disease (as per RECIST version 1.1)
Patient ability to comply with the collection of tumor biopsies, and tumors must be accessible for biopsy
Adequate bone marrow function as defined by: Absolute Neutrophil Count (ANC) of ≥ 1.5 x 109/L, platelet count of ≥ 100 x 109/L, and hemoglobin of ≥ 9 g/dL)
Adequate liver function, as determined by a serum total bilirubin ≤ 1.5 Upper Limit of Normal (ULN), AST and ALT ≤ 3 x ULN (≤ 5 x ULN if liver metastases)
Adequate renal function, as determined by a serum creatinine ≤ 1.5 x ULN
Provision of signed written informed consent
Patient ability to comply with protocol requirements
If the patient is female
Patient must be postmenopausal, surgically sterile, or they must agree to use a physical barrier method of contraception in addition to either an intrauterine device or hormonal contraception until at least 6 months after termination of study drug, or must refrain from heterosexual activity during this same period
Patients of childbearing potential must have a negative pregnancy test within the seven days prior to the first study drug administration
If the patient is male: patient must abstain from heterosexual activity or must agree
to use an acceptable method of contraception (e.g. condom) during the study for at
least 6 months after termination of study drug
Patients covered by a health insurance system
Specific Part II
Triple negative breast cancer and/or ovary cancer for the two first expansion cohorts
Whatever lines of treatment with a previous treatment of taxane family

Exclusion Criteria

Arm B: Allergy or hypersensitivity to components of the paclitaxel formulation
Patients with known or suspected Central Nervous System (CNS) metastases including
Allergy or hypersensitivity to PEP-010 formulation (Trehalose, Tween 20)
leptomenigeal metastasis (except patients with radiographically stable, asymptomatic
previously irradiated lesion provided patient is ≥ 3 weeks beyond completing cranial
irradiation)
Evidence of significant, uncontrolled concomitant diseases, which could affect
compliance with the protocol or interpretation of results, including significant
cardiovascular disease (such as New York Heart Association Class III or IV cardiac
disease, myocardial infarction within the last 6 months, unstable arrhythmias, or
Patients with acute infection
unstable angina), or pulmonary disease (including obstructive pulmonary disease and
history of symptomatic bronchospasm)
Patients with known HIV, HBV and HCV infections
Concomitant cancer in the past 3 years except prostate cancer controlled by hormone
therapy, cutaneous cancers (except melanoma) and in situ carcinoma
Pregnant or lactating women
Prior chemotherapy, radiotherapy (other than short cycle of palliative radiotherapy)
immunotherapy within 21 days of first receipt of study drug
Person deprived of liberty or under guardianship
Prior investigational agent within 28 days of first PEP-010 administration
Hormone therapy within 14 days of first receipt of study drug, with exception of
Gonadotropin-Releasing Hormone (GnRH) or Luteinizing-Hormone-Releasing Hormone (LHRH)
agonists used for advanced prostate cancer, if indicated
Prior relevant toxicities from chemotherapy or radiotherapy which have not regressed
to grade ≤1 severity except alopecia (NCI-CTCAE version 5.0)
Any other uncontrolled diseases, metabolic dysfunction, physical examination finding
or clinical laboratory finding or any other medical condition that, in the opinion of
the investigator, contraindicates the use of an investigational drug, or will impose
excessive risk to the patient
Patients with known Sars-Cov-2 infection
Patients with altered mental status or psychiatric disorder that, in the opinion of
the investigator, would preclude a valid patient informed consent
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