NCT03894540

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

Terminated Phase 1 Results posted Last updated 13 September 2022

What this trial tests

Phase 1 trial testing IPN60090 in Solid Tumor in 22 participants. Terminated before completion.

Timeline

22 March 2019

Primary endpoint
21 December 2020

21 December 2020

Quick facts

Lead sponsor	Ipsen
Phase	Phase 1
Status	Terminated
Study type	INTERVENTIONAL
Allocation	non randomized
Design	sequential
Masking	none
Primary purpose	treatment
Enrollment	22
Start date	22 March 2019
Primary completion	21 December 2020
Estimated completion	21 December 2020
Sites	1 location across United States

Drugs / interventions tested

• IPN60090 — full drug profile →
• pembrolizumab (pembrolizumab) — full drug profile →
• paclitaxel — full drug profile →
• IPN60090 single administration

Conditions studied

• Solid Tumor — all drugs for Solid Tumor →

Sponsor

Ipsen — full company profile →

Who can join

18 and older, any sex, with Solid Tumor. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

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

Any TEAEs

Group	Value	95% CI
IPN60090 20 mg	1
IPN60090 40 mg	1
IPN60090 80 mg	1
IPN60090 120 mg	4
IPN60090 180 mg	11
IPN60090 240 mg	4

TEAEs with NCI-CTCAE 5.0 Grade 3/4/5

Group	Value	95% CI
IPN60090 20 mg	1
IPN60090 40 mg	1
IPN60090 80 mg	1
IPN60090 120 mg	2
IPN60090 180 mg	8
IPN60090 240 mg	3

Treatment emergent SAEs

Group	Value	95% CI
IPN60090 20 mg	1
IPN60090 40 mg	0
IPN60090 80 mg	1
IPN60090 120 mg	2
IPN60090 180 mg	4
IPN60090 240 mg	3

TEAEs leading to study treatment discontinuation

Group	Value	95% CI
IPN60090 20 mg	0
IPN60090 40 mg	0
IPN60090 80 mg	0
IPN60090 120 mg	0
IPN60090 180 mg	1
IPN60090 240 mg	0

TEAEs leading to interruption or decrease of study treatment

Group	Value	95% CI
IPN60090 20 mg	0
IPN60090 40 mg	0
IPN60090 80 mg	0
IPN60090 120 mg	2
IPN60090 180 mg	6
IPN60090 240 mg	1

TEAEs leading to interruption of study treatment

Group	Value	95% CI
IPN60090 20 mg	0
IPN60090 40 mg	0
IPN60090 80 mg	0
IPN60090 120 mg	2
IPN60090 180 mg	6
IPN60090 240 mg	1

Number of Participants With Dose-Limiting Toxicities (DLT) in Cycle 1 of Part A Primary · Up to Cycle 1 Day 21 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).

Group	Value	95% CI
IPN60090 20 mg	0
IPN60090 40 mg	0
IPN60090 80 mg	0
IPN60090 120 mg	0
IPN60090 180 mg	0
IPN60090 240 mg	0

Recommended Dose of IPN60090 in Part A Primary · Up to Cycle 1 Day 21 of 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.

Group	Value	95% CI
DLT Evaluable Population Analysis Set	180

Best Overall Response (BOR) in Part A Secondary · 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).

The BOR is defined as the best response designation \[in the order of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD)\] for each participant that is recorded between the date of the first dose of the study drug and the date of documented disease progression per RECIST 1.1 or the date of subsequent anticancer therapy whichever occurs first. Per RECIST v1.1, CR is disappearance of all target lesions; PR is \>=30% decrease in the sum of the longest diameter of target lesions; and overall response = CR + PR.

Group	Value	95% CI
IPN60090 20 mg	0
IPN60090 40 mg	0
IPN60090 80 mg	0
IPN60090 120 mg	0
IPN60090 180 mg	0
IPN60090 240 mg	0
IPN60090 20 mg	0
IPN60090 40 mg	0
IPN60090 80 mg	0
IPN60090 120 mg	0
IPN60090 180 mg	0
IPN60090 240 mg	0
IPN60090 20 mg	1
IPN60090 40 mg	1
IPN60090 80 mg	1
IPN60090 120 mg	3
IPN60090 180 mg	9
IPN60090 240 mg	2
IPN60090 20 mg	0
IPN60090 40 mg	0
IPN60090 80 mg	0
IPN60090 120 mg	1
IPN60090 180 mg	2
IPN60090 240 mg	2

Objective Response Rate (ORR) in Part A Secondary · 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).

The ORR is defined as the percentage of participants in whom the BOR is equal to CR and PR for Part A. The BOR is defined as the best response designation (in the order of CR, PR, SD, PD) for each participant that is recorded between the date of the first dose of the study drug and the date of documented disease progression per RECIST 1.1 or the date of subsequent anticancer therapy whichever occurs first. Per RECIST v1.1, CR is disappearance of all target lesions; PR is \>=30% decrease in the sum of the longest diameter of target lesions; and overall response = CR + PR.

Group	Value	95% CI
IPN60090 20 mg	0	0.0 – 97.5
IPN60090 40 mg	0	0.0 – 97.5
IPN60090 80 mg	0	0.0 – 97.5
IPN60090 120 mg	0	0.0 – 60.2
IPN60090 180 mg	0	0.0 – 28.5
IPN60090 240 mg	0	0.0 – 60.2

Disease Control Rate (DCR) in Part A Secondary · 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).

The DCR is defined as the percentage of participants in whom the BOR is equal to CR, PR or SD for Part A. The BOR is defined as the best response designation (in the order of CR, PR, SD, PD) for each participant that is recorded between the date of the first dose of the study drug and the date of documented disease progression per RECIST 1.1 or the date of subsequent anticancer therapy whichever occurs first. Per RECIST v1.1, CR is disappearance of all target lesions; PR is \>=30% decrease in the sum of the longest diameter of target lesions; and overall response = CR + PR.

Group	Value	95% CI
IPN60090 20 mg	100.0	2.5 – 100.0
IPN60090 40 mg	100.0	2.5 – 100.0
IPN60090 80 mg	100.0	2.5 – 100.0
IPN60090 120 mg	75.0	19.4 – 99.4
IPN60090 180 mg	81.8	48.2 – 97.7
IPN60090 240 mg	50.0	6.8 – 93.2

Mean Progression Free Survival (PFS) in Part A Secondary · 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).

The PFS is defined as the time from first dose of study drug to the first documented objective disease progression (for RECIST 1.1), clinical disease progression collected at end of treatment, or death due to any cause, whichever occurred first. Per RECIST 1.1, progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Group	Value	95% CI
IPN60090 20 mg	4.90	± NA
IPN60090 40 mg	1.45	± NA
IPN60090 80 mg	2.73	± NA
IPN60090 120 mg	2.81	± 2.193
IPN60090 180 mg	4.37	± 2.766
IPN60090 240 mg	1.52	± 0.073

Mean Overall Survival (OS) in Part A Secondary · 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).

The OS is defined as the time from first dose of study drug to death due to any cause. Participants who were lost to follow-up or who were still alive at the time of analysis is censored at the last day the participant was known to be alive or data cut-off date, whichever occurred first.

Group	Value	95% CI
IPN60090 20 mg	5.03	± NA
IPN60090 40 mg	6.21	± NA
IPN60090 80 mg	13.24	± NA
IPN60090 120 mg	6.35	± 4.433
IPN60090 180 mg	11.00	± 5.421
IPN60090 240 mg	11.01	± 4.409

Mean Best Percent Change From Baseline in the Sum of Diameters of the Target Lesions at Minimum Post-Baseline in Part A Secondary · Baseline (within 28 days before start of study drug) and post-baseline, up to data cut-off for study termination (maximum of 247 days).

All measurable lesions up to a maximum of two lesions per organ and five lesions in total, representative of all involved organs, identified as target lesions and measured at baseline. Baseline is defined as the last measurement prior to the first dose of study drug.

Group	Value	95% CI
IPN60090 20 mg	0.0	± NA
IPN60090 40 mg	7.7	± NA
IPN60090 80 mg	-21.6	± NA
IPN60090 120 mg	-10.2	± 14.48
IPN60090 180 mg	3.6	± 18.05
IPN60090 240 mg	18.3	± 20.88

Maximum Observed Concentration (Cmax) of IPN60090 in Part A Secondary · Pre-dose and 0.5, 1, 2, 4, 8 and 12 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 14 in Part A

Blood samples were collected to determine Cmax of IPN60090. The pharmacokinetics (PK) of IPN60090 plasma concentrations were performed using noncompartmental analysis.

Cycle 1 Day 1

Group	Value	95% CI
IPN60090 120 mg	10019	± 4429
IPN60090 180 mg	13467	± 8780
IPN60090 240 mg	13068	± 11503

Cycle 1 Day 14

Group	Value	95% CI
IPN60090 120 mg	19595	± 16103
IPN60090 180 mg	24395	± 9912
IPN60090 240 mg	25793	± 16215

Time to Reach Maximum Observed Concentration (Tmax) of IPN60090 in Part A Secondary · Pre-dose and 0.5, 1, 2, 4, 8 and 12 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 14 in Part A

Blood samples were collected to determine Tmax of IPN60090. The PK of IPN60090 plasma concentrations were performed using noncompartmental analysis.

Cycle 1 Day 1

Group	Value	95% CI
IPN60090 120 mg	2.10	1.00 – 4.08
IPN60090 180 mg	4.00	1.00 – 4.17
IPN60090 240 mg	4.04	1.08 – 4.13

Cycle 1 Day 14

Group	Value	95% CI
IPN60090 120 mg	1.00	0.93 – 2.00
IPN60090 180 mg	2.00	1.00 – 4.08
IPN60090 240 mg	1.58	0.00 – 4.00

Trough Plasma Concentration (Ctrough) of IPN60090 in Part A Secondary · Pre-dose and 0.5, 1, 2, 4, 8 and 12 hours post-dose on Cycle 1 Day 14 in Part A

Blood samples were collected to determine Ctrough of IPN60090. The PK of IPN60090 plasma concentrations were performed using noncompartmental analysis.

Group	Value	95% CI
IPN60090 120 mg	9211	± 8149
IPN60090 180 mg	14616	± 6654
IPN60090 240 mg	20214	± 15970

Adverse events — posted to ClinicalTrials.gov

Time frame: 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).. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

IPN60090 20 mg

Serious: 1/1 (100%)

Deaths: 0/1

IPN60090 40 mg

Serious: 0/1 (0%)

Deaths: 0/1

IPN60090 80 mg

Serious: 1/1 (100%)

Deaths: 0/1

IPN60090 120 mg

Serious: 2/4 (50%)

Deaths: 0/4

IPN60090 180 mg

Serious: 4/11 (36%)

Deaths: 0/11

IPN60090 240 mg

Serious: 3/4 (75%)

Deaths: 0/4

Serious adverse events (23 terms)

Reaction	System	IPN60090 20 mg	IPN60090 40 mg	IPN60090 80 mg	IPN60090 120 mg	IPN60090 180 mg	IPN60090 240 mg
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—
Haematochezia	Gastrointestinal disorders	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—
Small intestinal obstruction	Gastrointestinal disorders	—	—	—	—	—	—
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	—	—	—	—	—	—
Aeromonas infection	Infections and infestations	—	—	—	—	—	—
COVID-19	Infections and infestations	—	—	—	—	—	—
Clostridium difficile infection	Infections and infestations	—	—	—	—	—	—
Cryptosporidiosis infection	Infections and infestations	—	—	—	—	—	—
Pyelonephritis	Infections and infestations	—	—	—	—	—	—
Brain oedema	Nervous system disorders	—	—	—	—	—	—
Cerebrovascular accident	Nervous system disorders	—	—	—	—	—	—
Seizure	Nervous system disorders	—	—	—	—	—	—
Biliary obstruction	Hepatobiliary disorders	—	—	—	—	—	—
Cholecystitis	Hepatobiliary disorders	—	—	—	—	—	—
Pathological fracture	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—	—	—	—
Vertigo	Ear and labyrinth disorders	—	—	—	—	—	—
Blood bilirubin increased	Investigations	—	—	—	—	—	—
Hyponatraemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—
Acute kidney injury	Renal and urinary disorders	—	—	—	—	—	—

Other adverse events (79 terms — click to expand)

Reaction	System	IPN60090 20 mg	IPN60090 40 mg	IPN60090 80 mg	IPN60090 120 mg	IPN60090 180 mg	IPN60090 240 mg
Photopsia	Eye disorders	—	—	—	—	—	—
Photophobia	Eye disorders	—	—	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—
Hypertriglyceridaemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—	—
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—
Blood creatinine increased	Investigations	—	—	—	—	—	—
Rash pruritic	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Anxiety	Psychiatric disorders	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—
Abdominal distension	Gastrointestinal disorders	—	—	—	—	—	—
Dysphagia	Gastrointestinal disorders	—	—	—	—	—	—
Flatulence	Gastrointestinal disorders	—	—	—	—	—	—
Small intestinal obstruction	Gastrointestinal disorders	—	—	—	—	—	—
Abdominal pain lower	Gastrointestinal disorders	—	—	—	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—	—	—	—
Gastric haemorrhage	Gastrointestinal disorders	—	—	—	—	—	—
Oesophageal stenosis	Gastrointestinal disorders	—	—	—	—	—	—
Oesophagitis	Gastrointestinal disorders	—	—	—	—	—	—
Rectal haemorrhage	Gastrointestinal disorders	—	—	—	—	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Hyponatraemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Hypercalcaemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Hypocalcaemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—	—	—	—
Hyperkalaemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Hypomagnesaemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Hypophosphataemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Increased appetite	Metabolism and nutrition disorders	—	—	—	—	—	—
Vision blurred	Eye disorders	—	—	—	—	—	—
Visual impairment	Eye disorders	—	—	—	—	—	—

Most-reported serious reactions: Vomiting, Abdominal pain, Haematochezia, Nausea, Small intestinal obstruction, Upper gastrointestinal haemorrhage, Aeromonas infection, COVID-19.

Data from ClinicalTrials.gov NCT03894540 adverse events section.

Sponsor's own description

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).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeting cancer metabolism in the era of precision oncology.
   Stine ZE, Schug ZT, Salvino JM, Dang CV. · · 2022 · cited 839× · PMID 34862480 · DOI 10.1038/s41573-021-00339-6
2. A glutamine tug-of-war between cancer and immune cells: recent advances in unraveling the ongoing battle.
   Wang B, Pei J, Xu S, Liu J, et al · · 2024 · cited 81× · PMID 38459595 · DOI 10.1186/s13046-024-02994-0
3. Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma.
   Osman AA, Arslan E, Bartels M, Michikawa C, et al · · 2023 · cited 46× · PMID 36689560 · DOI 10.1158/1078-0432.ccr-22-2747
4. New Immunometabolic Strategy Based on Cell Type-Specific Metabolic Reprogramming in the Tumor Immune Microenvironment.
   Sung JY, Cheong JH. · · 2022 · cited 27× · PMID 35269390 · DOI 10.3390/cells11050768
5. Exploiting the Achilles' heel of cancer: disrupting glutamine metabolism for effective cancer treatment.
   Fan Y, Xue H, Li Z, Huo M, et al · · 2024 · cited 24× · PMID 38510646 · DOI 10.3389/fphar.2024.1345522
6. Immuno-Metabolism: The Role of Cancer Niche in Immune Checkpoint Inhibitor Resistance.
   Weng CY, Kao CX, Chang TS, Huang YH. · · 2021 · cited 24× · PMID 33514004 · DOI 10.3390/ijms22031258
7. The role of tumor metabolism in modulating T-Cell activity and in optimizing immunotherapy.
   Ganjoo S, Gupta P, Corbali HI, Nanez S, et al · · 2023 · cited 16× · PMID 37180129 · DOI 10.3389/fimmu.2023.1172931
8. Glutamine Metabolism and Prostate Cancer.
   Erb HHH, Polishchuk N, Stasyk O, Kahya U, et al · · 2024 · cited 14× · PMID 39199642 · DOI 10.3390/cancers16162871