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.
Primary Objective:
Parts 1 and 2:
- To evaluate the safety, tolerability, and to determine the MTD or RP2D of AMG 193 alone and in combination with docetaxel in adult subjects with metastatic or locally advanced MTAP-null solid tumors.
Part 3:
- To evaluate the ORR of AMG 193 in adult subjects with metastatic or locally advanced MTAP-null non-small cell lung cancer NSCLC, after prior treatment with chemotherapy and/or a PD-L1 inhibitor.
Secondary Objectives:
Parts 1 and 2:
- To characterize the PK of AMG 193 alone and in combination with docetaxel. To evaluate ORR, DCR, DoR,TTR, duration of SD, PFS, and OS of AMG 193 alone and in combination with docetaxel in adult subjects with MTAP-null solid tumors;
Part 3:
- To assess safety and tolerability of AMG 193 in metastatic or locally advanced MTAP-null NSCLC.
- To evaluate DCR, DoR, TTR, duration of SD, PFS, and OS of AMG 193 in metastatic or locally advance MTAP-null NSCLC.
AMG 193
Chemotherapy multiple agents systemic
- Rutgers Cancer Institute of New Jersey
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).
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.
- A total of 25 slides of 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.
- Part 1i: Enrollment criteria for Part 1i are to match the criteria of the expansion
arm from which the indication was selected.
- 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
Exclusion Criteria
- 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, unless anti-tumor therapy is a
therapy with 5 times the half-life being shorter than 28 days
- 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
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site ClinicalTrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356.