Dose Escalation and Dose Expansion Study of IPN60090 in Patients With Advanced Solid Tumours

NCT03894540 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: D-US-60090-0012018-003681-13
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the protocol is to determine safety, tolerability, recommended dose (RD), pharmacokinetics (PK), pharmacodynamics (PD) and preliminary anti-tumour activity of IPN60090 as a single agent (Part A) and in combination with pembrolizumab (Part B) or paclitaxel (Part C) in patients with advanced solid tumours and to evaluate food effect (Part D).

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) in Part A

  An adverse event (AE) is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a study drug, whether or not considered causally related to the study drug. An undesirable medical condition can be symptoms, signs or the abnormal results of an investigation. An SAE is any AE that: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; results in congenital anomaly or birth defect; or is medically important. A TEAE is defined as any AE that began or worsened following the first administration of study drugs. AEs were recorded and graded according of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0. * Grade 1 = mild, * Grade 2 = moderate, * Grade 3 = severe, * Grade 4 = life threatening/disabling, * Grade 5 = death (related to AE).

  TEAEs were to be collected from the start of the first dose of IPN60090 (Cycle 1 Day 1) up to 30 days after the date of the decision to permanently discontinue study treatment, assessed until data cut-off for study termination (maximum of 219 days).

• Number of Participants With Dose-Limiting Toxicities (DLT) in Cycle 1 of Part A

  The maximum tolerated dose (MTD) is defined as the maximum dose of IPN60090 administered BID for 21 days, so that no more than 30% of participants experience a DLT. The MTD was determined using a Bayesian Optimal Interval design. The DLT assessment period was the first 21 days of treatment (one cycle).

  Up to Cycle 1 Day 21 of Part A

• Recommended Dose of IPN60090 in Part A

  The recommended dose was determined by the safety review committee following an ad-hoc review of the safety and tolerability data during Part A of the study.

  Up to Cycle 1 Day 21 of Part A

Secondary Outcomes (14)

• Best Overall Response (BOR) in Part A

  RECIST assessments performed at baseline (within 28 days before start of study drug), every 6 weeks +/-1 week for first 24 weeks, then every 12 weeks +/-2 weeks thereafter. Up to data cut-off for study termination (maximum of 247 days).

• Objective Response Rate (ORR) in Part A

  RECIST assessments performed at baseline (within 28 days before start of study drug), every 6 weeks +/-1 week for first 24 weeks, then every 12 weeks +/-2 weeks thereafter. Up to data cut-off for study termination (maximum of 247 days).

• Disease Control Rate (DCR) in Part A

  RECIST assessments performed at baseline (within 28 days before start of study drug), every 6 weeks +/-1 week for first 24 weeks, then every 12 weeks +/-2 weeks thereafter. Up to data cut-off for study termination (maximum of 247 days).

• Mean Progression Free Survival (PFS) in Part A

  RECIST assessments performed at baseline (within 28 days before start of study drug), every 6 weeks +/-1 week for first 24 weeks, then every 12 weeks +/-2 weeks thereafter. Up to data cut-off for study termination (maximum of 247 days).

• Mean Overall Survival (OS) in Part A

  RECIST assessments performed at baseline (within 28 days before start of study drug), every 6 weeks +/-1 week for first 24 weeks, then every 12 weeks +/-2 weeks thereafter. Up to data cut-off for study termination (maximum of 247 days).

Study Arms (4)

IPN60090

EXPERIMENTAL

Part 1: Dose escalation of IPN60090, Part 2: Dose expansion IPN60090 given as a Bis in Die (BID) oral dose administered up to Maximum Tolerated Dose (MTD) over a 21-day cycle

Drug: IPN60090

IPN60090 in combination with pembrolizumab

EXPERIMENTAL

Part 1: Dose escalation of IPN60090 in combination with pembrolizumab, Part 2: Dose expansion IPN60090 given as a Bis in Die (BID) oral dose, starting with pharmacologically active dose identified in 1dose escalation of IPN60090 as a single agent, over a 21-day cycle in combination with 200 mg pembrolizumab given every 21 days (Day 1 of every cycle) as IV infusion

Drug: IPN60090; Drug: pembrolizumab

IPN60090 in combination with paclitaxel

EXPERIMENTAL

Part 1: Dose escalation of IPN60090 in combination with paclitaxel, Part 2: Dose expansion IPN60090 given as a BID oral dose, starting with pharmacologically active dose identified in dose escalation of IPN60090 as a single agent over a 21-day cycle in combination with 175 mg/m2 or 135 mg/m2 paclitaxel given every 21 days (Day 1 of every cycle) as IV infusion

Drug: IPN60090; Drug: paclitaxel

IPN60090 food effect

EXPERIMENTAL

Part 1: Food Effect of IPN60090 IPN60090 given as a single oral dose as a single agent at the recommended dose (RD) under fasting and fed conditions followed by IPN60090 given as a BID oral dose administered at the RD over a 21-day cycle.

Drug: IPN60090 single administration

Interventions

IPN60090 DRUG

Oral capsules given daily

IPN60090; IPN60090 in combination with paclitaxel; IPN60090 in combination with pembrolizumab

pembrolizumab DRUG

An intravenous solution in single-use vial to be diluted for infusion.

IPN60090 in combination with pembrolizumab

paclitaxel DRUG

An intravenous solution in single-use vial to be diluted for infusion.

IPN60090 in combination with paclitaxel

IPN60090 single administration DRUG

Oral capsules given once

IPN60090 food effect

Eligibility Criteria

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

You may qualify if:

• Male or female patients ≥18 years of age
• Patients with solid tumours who have received at least one line of therapy for advanced disease
• Measurable or non-measurable evaluable disease per RECIST 1.1
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤1
• Standard of care and/or any investigational therapies must have been completed at least 3 weeks prior to treatment

You may not qualify if:

• Prior malignancy within the previous 2 years except for locally curable cancers that have been cured, such as basal or squamous cell skin cancer, or carcinoma in situ of the cervix, breast or bladder
• Known primary central malignancy or symptomatic central nervous system metastasis
• Major surgical intervention within 28 days before study drug administration
• Significant acute or chronic infections

Sponsors & Collaborators

• Ipsen: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Interventions

pembrolizumab; Paclitaxel

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Limitations and Caveats

The study was terminated by the sponsor following an internal portfolio review during the dose escalation phase (Part A). The early termination was not due to any safety or tolerability issues with IPN60090.

Results Point of Contact

• Title: Medical Director
• Organization: Ipsen

clinical.trials@ipsen.com

see email

Study Officials

• Ipsen Medical Director

  Ipsen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: March 27, 2019
• First Posted: March 28, 2019
• Study Start: March 22, 2019
• Primary Completion: December 21, 2020
• Study Completion: December 21, 2020
• Last Updated: September 13, 2022
• Results First Posted: November 22, 2021

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)