Informations générales (source: ClinicalTrials.gov)
A Phase 1/1b/2 Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 193 Alone and in Combination With Docetaxel in Subjects With Advanced MTAP-null Solid Tumors
Interventional
Phase 1/Phase 2
Amgen (Voir sur ClinicalTrials)
février 2022
novembre 2028
13 septembre 2025
The primary objective of Parts 1 and 2 of this study is to evaluate the safety,
tolerability, and to determine the maximum tolerated dose (MTD) or recommended phase 2
dose (RP2D) of AMG 193 alone and in combination with docetaxel in adult participants with
metastatic or locally advanced methylthioadenosine phosphorylase (MTAP)-null solid
tumors.
The primary objective of Part 3 of this study is to evaluate the efficacy of AMG 193 in
adult participants with metastatic or locally advanced MTAP-null solid tumors.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Sophie POSTEL-VINAY | 29/04/2024 17:17:40 | Contacter | ||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Georges Francois Leclerc - 21000 - Dijon - France | Contact (sur clinicalTrials) | ||||
| Centre Oscar Lambret - 59000 - Lille - France | Contact (sur clinicalTrials) | ||||
| Hopitaux Universitaires Pitie Salpetriere - Charles Foix - 75013 - Paris - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
Inclusion Criteria:
- Participant has provided informed consent/assent before initiation of any study
specific activities/procedures.
- Age ≥ 18 years.
- Evidence of homozygous loss of cyclin dependent kinase inhibitor 2A (CDKN2A) (null)
(Parts 1a, 1j, 1k, and 2a only) and/or methylthioadenosine phosphorylase (MTAP)
(null) in the tumor tissue or blood (Parts 1a to 1k, Parts 2a and 2b) or lost MTAP
expression in the tumor tissue (Parts 1a to 1k, Parts 2a and 2b).
- Histologically confirmed metastatic or locally advanced solid tumor not amenable to
curative treatment with surgery and/or radiation.
- Able to swallow and retain orally (PO) administered study treatment and willing to
record daily adherence to investigational product.
- Disease measurable as defined by Response Evaluation Criteria in Solid Tumors
Version 1.1 (RECIST v1.1). Note: except participants enrolling to Part 1m.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
- Adequate hematopoietic function per local laboratory
- Adequate renal function per local laboratory
- Adequate glucose control per local laboratory (Part 1 only)
- Adequate liver function per local laboratory
- Adequate coagulation parameters
- Adequate pulmonary function
- Adequate cardiac function
- Minimum life expectancy of 12 weeks as per investigator judgement.
- Archived tumor tissue (formalin-fixed, paraffin-embedded [FFPE] sample collected
within 5 years) or an archival block must be available.
- For Part 1f (MTAP-null or lost MTAP expression HNSCC): Must be willing to undergo
tumor biopsy.
- For Part 1a: Must be willing to undergo tumor biopsy, before start of treatment
(archival sample acceptable if obtained with 6 months of enrollment and subject has
not received any other treatment since sample was obtained) and while on treatment.
- For DSPS study (Part 1j): Must be willing to participate in DSPS substudy (US sites
only).
Food Effect Substudy (Part 1k): Specific Inclusion Criteria
- Subject able and willing to eat a standardized high-fat, high-caloric meal
- Subject able and willing to fast for ≥ 6 hours
Specific Inclusion Criteria for subjects with glioma (Part 1m only)
- Disease measurable as defined per Modified Response Assessment in Neuro-Oncology
Criteria 2.0 (mRANO 2.0)
- Participant has provided informed consent/assent before initiation of any study
specific activities/procedures.
- Age ≥ 18 years.
- Evidence of homozygous loss of cyclin dependent kinase inhibitor 2A (CDKN2A) (null)
(Parts 1a, 1j, 1k, and 2a only) and/or methylthioadenosine phosphorylase (MTAP)
(null) in the tumor tissue or blood (Parts 1a to 1k, Parts 2a and 2b) or lost MTAP
expression in the tumor tissue (Parts 1a to 1k, Parts 2a and 2b).
- Histologically confirmed metastatic or locally advanced solid tumor not amenable to
curative treatment with surgery and/or radiation.
- Able to swallow and retain orally (PO) administered study treatment and willing to
record daily adherence to investigational product.
- Disease measurable as defined by Response Evaluation Criteria in Solid Tumors
Version 1.1 (RECIST v1.1). Note: except participants enrolling to Part 1m.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
- Adequate hematopoietic function per local laboratory
- Adequate renal function per local laboratory
- Adequate glucose control per local laboratory (Part 1 only)
- Adequate liver function per local laboratory
- Adequate coagulation parameters
- Adequate pulmonary function
- Adequate cardiac function
- Minimum life expectancy of 12 weeks as per investigator judgement.
- Archived tumor tissue (formalin-fixed, paraffin-embedded [FFPE] sample collected
within 5 years) or an archival block must be available.
- For Part 1f (MTAP-null or lost MTAP expression HNSCC): Must be willing to undergo
tumor biopsy.
- For Part 1a: Must be willing to undergo tumor biopsy, before start of treatment
(archival sample acceptable if obtained with 6 months of enrollment and subject has
not received any other treatment since sample was obtained) and while on treatment.
- For DSPS study (Part 1j): Must be willing to participate in DSPS substudy (US sites
only).
Food Effect Substudy (Part 1k): Specific Inclusion Criteria
- Subject able and willing to eat a standardized high-fat, high-caloric meal
- Subject able and willing to fast for ≥ 6 hours
Specific Inclusion Criteria for subjects with glioma (Part 1m only)
- Disease measurable as defined per Modified Response Assessment in Neuro-Oncology
Criteria 2.0 (mRANO 2.0)
- Spinal cord compression or untreated brain metastases or leptomeningeal disease.
- History of other malignancy within the past 2 years
- Any evidence of current interstitial lung disease
- Active infection
- Evidence of active severe acute respiratory syndrome coronavirus 2 (SARS-COV2)
infection.
- History of arterial thrombosis
- Myocardial infarction and/or symptomatic congestive heart failure.
- Gastrointestinal tract disease
- History of bowel obstruction, abdominal fistula, gastrointestinal perforation, or
intra-abdominal abscess
- History of solid organ transplant.
- Diagnosis of Congenital Short QT Syndrome.
- Major surgery
- Anti-tumor therapy within 28 days of study day 1.
- Prior treatment with an methionine adenosyltransferase 2α (MAT2A) inhibitor or a
protein arginine methyltransferase 5 (PRMT5) inhibitor.
- Prior treatment with docetaxel (Part 2 only)
- Prior irradiation to 25% of the bone marrow.
- Therapeutic or palliative radiation therapy within 2 weeks of study day 1.
- Live vaccine therapy within 4 weeks before study drug administration.
- Use of therapeutic anti-coagulation for treatment of active thromboembolic events.
- Use of prescription medications that are known strong inducers of cytochrome P450
3A4 (CYP3A4) within 14 days or 5 half-lives (whichever is longer) before study day 1
- Unresolved toxicity from prior anti-cancer therapy
- Currently receiving treatment in another investigational device or drug study.
- Known positive test for Human Immunodeficiency Virus (HIV).
- Positive hepatitis B surface antigen
- positive hepatitis C virus ribonucleic acid (RNA) by polymerase chain reaction (PCR)
- Female participants of childbearing potential unwilling to use protocol specified
method of contraception