A phase 1/1b/2 study of AMG 193 alone and in combination with docetaxel in subjects with advanced MTAP-null solid tumors.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amgen Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

13 May 2022 → ongoing

Decision date (initial)

2024-09-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Amgen Inc.

External identifiers

EU CT number

2023-504363-17-00

EudraCT number

2021-004764-10

WHO UTN

U1111-1309-0405

ClinicalTrials.gov

NCT05094336

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Others, Safety, Pharmacodynamic, Dose response, Efficacy, Pharmacokinetic

Part 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 tumor. Part 3: To evaluate the efficacy of AMG 193 in adult subjects with metastatic or locally advanced MTAP-null solid tumors.

Secondary objectives 4

1. Part 1 and 2: To characterize the PK of AMG 193 alone and in combination with docetaxel.
2. Part 1 and 2: To evaluate the preliminary antitumor activity of AMG 193 alone and in combination with docetaxel in adult subjects with MTAP-null solid tumors.
3. Part 3: To assess safety and tolerability of AMG 193 in metastatic or locally advanced MTAP-null solid tumors.
4. Part 3: To evaluate DCR, DoR, TTR, duration of DC, PFS, and OS of AMG 193 in metastatic or locally advanced MTAP-null solid tumors.

Conditions and MedDRA coding

Advanced MTAP-null solid tumors

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Evidence of homozygous loss of CDKN2A (null) and/or MTAP (null) by NGS or central IHC
2. Age ≥ 18 years
3. Histologically confirmed metastatic or locally advanced solid tumor not amenable to curative treatment with surgery and/or radiation.
4. Able to swallow and retain PO administered study treatment and willing to record daily adherence to investigational product.
5. Disease measurable as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1).
6. Adequate hematopoietic function.
7. Adequate renal function.
8. Adequate liver function.
9. Adequate pulmonary function.
10. Adequate cardiac function.

Exclusion criteria 8

1. Prior treatment with an MAT2A inhibitor or a PRMT5 inhibitor.
2. Spinal cord compression or untreated brain metastases or leptomeningeal disease.
3. Gastrointestinal tract disease causing the inability to take PO medication, malabsorption syndrome, requirement for IV alimentation, gastric/jejunal tube feeds, uncontrolled inflammatory gastrointestinal disease.
4. History of bowel obstruction, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months before study entry.
5. Prior irradiation to > 25% of the bone marrow.
6. Use of prescription medications that are known strong inducers or inhibitors of CYP3A4 within 14 days or 5 half-lives before study day 1.
7. Major surgery within 28 days before first dose of AMG 193
8. Evidence of Hepatitis B or C infection

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Part 1 and 2: DLTs, treatment-emergent adverse events, serious adverse events, and changes in vital signs, ECGs, and clinical laboratory tests.
2. Part 3: Objective response (defined as best overall response of confirmed CR or PR based on RECIST v1.1) derived utilizing investigator tumor assessments.

Secondary endpoints 9

1. Part 1 and 2: PK parameters of AMG 193 alone and in combination with docetaxel.
2. PK parameters of docetaxel (Parts 2a and 2b only) in combination with AMG 193 after multiple doses.
3. Part 1 and 2 Objective response (defined as the best overall response of confirmed CR or PR based on RECIST v1.1)
4. Disease Control (DC)
5. Duration of Response (DoR)
6. Duration of disease control (DoDC)
7. Time to Response (TTR)
8. Overall Survival (OS)
9. Progression-Free Survival (PFS)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amgen Inc.

Sponsor organisation

Amgen Inc.

Address

1 Amgen Center Drive

City

Thousand Oaks

Postcode

91320-1799

Country

United States

Scientific contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Public contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Third parties 14

Locations

4 EU/EEA countries · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 40 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications