A Phase 1/2 Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Anvumetostat in Combination With IDE397 in Subjects With Advanced MTAP-null Solid Tumors

Plain English Summary

A Phase 1/2 Study of Anvumetostat in Combination With IDE397 in Participants With Advanced Methylthioadenosine Phosphorylase (MTAP)-Null Solid Tumors is a Phase 2 clinical trial sponsored by Amgen studying MTAP-null Non-Small-Cell Lung Cancer, MTAP-null Solid Tumors. This study tests a combination of two drugs, Anvumetostat and IDE397, to see if they are safe and effective for treating advanced solid tumors that lack a specific gene (MTAP-null). It is for adults with advanced or metastatic solid tumors that are MTAP-null and have not responded to standard treatments, or specifically for MTAP-null Non-Small-Cell Lung Cancer (NSCLC) that has progressed after prior therapies. Participants will take both drugs by mouth. The study involves finding the right dose and then evaluating how well the combination shrinks tumors. There are no specific alternative treatments mentioned in this summary, but standard therapies for advanced cancers are generally available. The trial aims to enroll 53 participants.

Official Summary

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 Anvumetostat 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 anvumetostat in combination with IDE397 in adult participants with metastatic or locally advanced MTAP-null Non-Small-Cell Lung Cancer (NSCLC).

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults with advanced solid tumors that have a specific genetic marker (MTAP-null or MTAP deletion). For Part 2, patients must have Non-Small-Cell Lung Cancer (NSCLC) that has progressed after 1-2 previous treatments. Patients must be able to swallow pills and have adequate organ function. Individuals who have previously received drugs targeting similar pathways (MAT2A or PRMT5 inhibitors) or have untreated brain metastases or spinal cord compression cannot participate. This trial is studying MTAP-null Non-Small-Cell Lung Cancer, MTAP-null Solid Tumors, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures will determine if the drug combination is safe, identify the best dose, and assess if it can shrink tumors in patients with advanced MTAP-null Non-Small-Cell Lung Cancer. The specific primary outcome measures are: Part 1: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) (Day 1 up to Day 21); Part 1: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) (Day 1 up to approximately 2.5 years); Part 1: Number of Participants Experiencing Serious Adverse Events (SAEs) (Day 1 up to approximately 2.5 years); Part 2: Objective Response (OR) per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Day 1 up to approximately 2.5 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a gap in treatment for rare cancers driven by a specific genetic mutation (MTAP-null), offering a new combination therapy approach. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets MTAP-null Non-Small-Cell Lung Cancer, MTAP-null Solid Tumors, where improved treatment options are needed.

Investor Insight

This trial targets a specific genetic vulnerability in cancer, potentially opening a new treatment avenue for a subset of patients. Success could lead to a new therapy for a niche but significant mark Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific risks and benefits of Anvumetostat and IDE397, and how this combination might affect your current health. Be prepared to take oral medications daily and attend regular clinic visits for monitoring, including blood tests and scans. You may need to provide archived tumor tissue or undergo a biopsy to confirm the MTAP-null status before starting treatment. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 53 participants

Interventions

• DRUG: Anvumetostat — Administered PO
• DRUG: IDE397 — Administered PO

Primary Outcomes

• Part 1: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) (Day 1 up to Day 21)
• Part 1: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) (Day 1 up to approximately 2.5 years)
• Part 1: Number of Participants Experiencing Serious Adverse Events (SAEs) (Day 1 up to approximately 2.5 years)
• Part 2: Objective Response (OR) per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Day 1 up to approximately 2.5 years)

Secondary Outcomes

• Part 1 and 2: Maximal Plasma Concentration (Cmax) of Anvumetostat (Day 1 pre-dose up to Cycle 5 (Cycle= 21 days))
• Part 1 and 2: Cmax of IDE397 (Day 1 pre-dose up to Cycle 5 (Cycle= 21 days))
• Part 1 and 2: Time to Achieve Maximal Plasma Concentration (Tmax) of Anvumetostat (Day 1 pre-dose up to Cycle 5 (Cycle= 21 days))
• Part 1 and 2: Tmax of IDE397 (Day 1 pre-dose up to Cycle 5 (Cycle= 21 days))
• Parts 1 and 2: Area Under The Curve (AUC) After Single Dose of Anvumetostat (Day 1 pre-dose up to Cycle 5 (Cycle= 21 days))

Full Eligibility 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 Locations

• City of Hope National Medical Center, Duarte, California, United States
• Sarah Cannon Research Institute, Denver, Colorado, United States
• Community Health Network MD Anderson Cancer Center - North, Indianapolis, Indiana, United States
• Dana Farber Cancer Institute, Boston, Massachusetts, United States
• University of Michigan, Ann Arbor, Michigan, United States
• Health Partners Cancer Center at Regions Hospital, Saint Paul, Minnesota, United States
• Astera Cancer Care, East Brunswick, New Jersey, United States
• New York University Grossman School of Medicine and New York University Langone Hospitals, New York, New York, United States
• Columbia University Irving Medical Center, New York, New York, United States
• Memorial Sloan Kettering Cancer Center, New York, New York, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Non-Small-Cell Lung Cancer
• Solid Tumors
• Oncology
• Cancer Genetics
• Targeted Therapy
• Pharmacokinetics
• Pharmacodynamics
• Drug Development
• Clinical Trials
• Metastatic Cancer

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