A Phase 1/2 Study of AMG 193 in Combination With IDE397 in Participants With Advanced Methylthioadenosine Phosphorylase (MTAP)-Null Solid Tumors

Amgen

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: MTAP-null Non-Small-Cell Lung Cancer; MTAP-null Solid Tumors

Treatments: Drug: AMG 193; Drug: IDE397

Study type: Interventional

Funder types: Industry

Identifiers

NCT05975073

20220127

Details and patient eligibility

About

The main aims of this study are to evaluate the safety and tolerability, and to determine the maximum tolerated dose (MTD) or the recommended combination dose of AMG 193 in combination with IDE397 in adult participants with metastatic or locally advanced MTAP-null solid tumors, and to evaluate the preliminary anti-tumor activity of AMG 193 in combination with IDE397 in adult participants with metastatic or locally advanced MTAP-null Non-Small-Cell Lung Cancer (NSCLC).

Enrollment: 53 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

1. Evidence of homozygous loss of MTAP (null) and/or MTAP deletion.

2. Presence of advanced/metastatic solid tumor not amenable to curative treatment

   1. Part 1: MTAP-null or lost MTAP expression solid tumor for which no standard therapy exists
   2. Part 2: MTAP-null or lost MTAP expression NSCLC with progression after 1 to 2 prior lines of systemic therapy.

3. Able to swallow and retain PO administered study treatment and willing to record adherence to investigational product

4. Disease measurable as defined by RECIST v1.1

5. Adequate organ function as defined in the protocol.

6. Archived tumor tissue. Participants without archived tumor tissue available may be allowed to enroll by undergoing tumor biopsy before cycle 1 day 1 dosing.

Exclusion Criteria

1. Prior treatment with an MAT2A inhibitor or a PRMT5 inhibitor.
2. Radiologic or clinical evidence of spinal cord compression, untreated or symptomatic brain metastases or leptomeningeal disease.
3. Cardiovascular and pulmonary exclusion criteria as defined in the protocol.
4. Gastrointestinal tract disease causing the inability to take PO medication, malabsorption syndrome, requirement for IV alimentation, gastric/jejunal tube feeds, uncontrolled inflammatory gastrointestinal disease (eg, Crohn's disease, ulcerative colitis)
5. History of bowel obstruction, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of study entry.
6. Prior irradiation to > 25% of the bone marrow
7. Use of prescription medications that are known strong CYP3A4/5 inducers or strong CYP3A4/5 inhibitors within 7 days for CYP3A4/5 inhibitors, 14 days for CYP3A4/5 inducers or 5 half-lives, whichever is longer, prior to any dose of investigational medical product.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

53 participants in 2 patient groups

Part 1: Dose Exploration of AMG 193 Combined With IDE397

Experimental group

Description:

Participants will receive escalating doses of AMG 193 and IDE397 administered orally (PO) in cycles of 21 days.

Treatment:

Drug: IDE397

Drug: AMG 193

Part 2: Dose Expansion of AMG 193 Combined With IDE397

Experimental group

Description:

AMG 193 and IDE397 will be administered PO in cycles of 21 days.

Treatment:

Drug: IDE397

Drug: AMG 193