First-in-human Phase I to Evaluate PEP-010 as Single Agent and in Combination With Paclitaxel or With Gemcitabine (CleverPeptide)

NCT04733027 | Active Not Recruiting Early Phase 1 DMC

• 1 other identifier: IC 2018-06
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 4

Brief 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 or with gemcitabine PEP-010 will be administered, in a Part 1, 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, and in a Part 2 only in combination in: Cohort 1 (expansion cohort, phase 1b): metastatic pancreatic ductal carcinoma (PDAC) who received at least one previous systemic chemotherapy and eligible for paclitaxel therapy. Cohort 2 (dose escalation cohort, phase 1a): metastatic pancreatic ductal carcinoma or advanced/metastatic ovarian cancer (OC) eligible for gemcitabine-based therapy

Conditions

Metastatic Solid Tumor Cancer

Outcome Measures

Primary Outcomes (2)

• For Part 1 (Dose escalation) and Part 2 (Cohort 2), the primary endpoints are the rate of occurrence of DLT within cycle 1 (21 days) after initiation of the study treatment for both parts.

  The DLT is defined as any clinically significant non-hematological toxicity ≥ grade 3 and any hematological toxicity ≥ grade 4 of treatment-related adverse event

  21 days after study treatment initiation

• Part 2 Cohort 1: The primary endpoint is the ORR (objective response rate), based on local investigator assessment, per RECIST 1.1.

  the ORR (objective response rate), defined as the proportion of patients who have achieved a complete response (CR) or partial response (PR) within the first 6 months

  6 months after study treatment initiation

Study Arms (2)

Part 2 cohort 1 : PEP010 in combination with paclitaxel

EXPERIMENTAL

Fort part 2 the Cohort 1 will include patients with PDAC treated with the combination of PEP-010 at the dose of 2.5 mg/kg and weekly paclitaxel 80 mg/m².

Combination Product: Dose escalation, first-in-human phase I clinical trial with an Expansion phase

Part 2 cohort 2 : PEP010 in combination with gemcitabine

EXPERIMENTAL

In arm B, the dose escalation phase will begin with DL4 (1.2 mg/kg) and will follow a 3+3 design For part 2 Cohort 2 will include patients with PDAC or OC treated with the combination of PEP-010 in ascending doses, and gemcitabine at 1000 mg/m2. Four doses of PEP-010 will be tested: 1.2 mg/kg, 2.5 mg/kg, 5 mg/kg and 10 mg/kg, according to a 3+3 dose escalation design. Once a MTD is achieved, and in light of safety, PK, and PD data, two dosing schedules will be further explored based on TSC recommendations. Each dosing schedule will be evaluated in a separate cohort to generate more data and inform on the choice of the RP2D, as per the recommendations of the FDA (Project Optimus). Patients will be randomized simultaneously in the two dose cohorts, each would include approximately 6 - 10 patients.

Combination Product: Dose escalation, first-in-human phase I clinical trial with an Expansion phase

Interventions

Dose escalation, first-in-human phase I clinical trial with an Expansion phase COMBINATION_PRODUCT

PEP-010 will be administered on days 1, 2 and 3 every week, as a 3-hour intravenous infusion. 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.

Part 2 cohort 1 : PEP010 in combination with paclitaxel; Part 2 cohort 2 : PEP010 in combination with gemcitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Part 1 Arms A and B:
• 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.

Sponsors & Collaborators

• Institut Curie: lead

Study Sites (4)

CLCC F.Baclesse Caen

Caen, France

Location

Institut Curie

Paris, 75005, France

Location

Institut de Cancerologie de l'Ouest- ICO

Saint-Herblain, 44805, France

Location

Gustave Roussy

Villejuif, France

Location

Related Publications (1)

• 1.Ezzalfani M. et al. The role of the expansion cohort in phase I trials in oncology: guidelines of the phase I HUB. Bull Cancer. 2015 Jan;102(1):73-82. doi:10.1016/j.bulcan. 2014.10.001. Epub 2015 Jan 2. Review. French. 2.M3(R2) guideline : Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals 3.ICH S9 - Nonclinical Evaluation for Anticancer Pharmaceuticals EMEA/CHMP/ICH/646107/2008 4.Masini et al. Histamin-releasing properties of polysorbate 80 in vitro and in vivo: correlation 1254 with its hypotensive action in the dog. Agents Actions 1985 Sep; 16(6):470-7. 5.Guideline on repeated dose toxicity - CPMP/SWP/1042/99 Rev 1 6.Storer B.E. Design and Analysis of Phase I Clinical Trials. Biometrics, Vol. 45, No. 3 (Sep., 1989), pp. 925-937. 7.Seshan V.E. et al. Clinical Trial Design and Data Analysis Functions, Package clinfun, version 1.0.15 (Apr 2018)

  BACKGROUND

Study Officials

• Marie-Paule SABLIN, MD, PhD

  Institut Curie

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Part 1 dose escalation Part 2 expansion cohort and short dose escalation cohort Randomization in the escalation dose cohort once MTD defined

Study Record Dates

• First Submitted: January 22, 2021
• First Posted: February 1, 2021
• Study Start: May 18, 2021
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): January 31, 2027
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data requests can be submitted starting 9 months after last article publication and will made accessible for up to 12 months.
• Access Criteria: Access to trial individual participant data can be requested by qualified researchers engaging in independent scientific reserach, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a data sharing agreement (DSA).

Locations

FR (4)