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

Plain English Summary

A Study of Anvumetostat in Participants With Advanced MTAP-null Solid Tumors (MTAPESTRY 101) is a Phase 2 clinical trial sponsored by Amgen studying Advanced MTAP-null Solid Tumors. This trial tests a new drug called Anvumetostat, alone or with chemotherapy (docetaxel), in adults with advanced solid tumors that have a specific genetic change (MTAP-null). It is for patients with advanced solid tumors that have a specific genetic marker (MTAP-null) and are not responding to standard treatments. Participation involves taking Anvumetostat by mouth, and possibly receiving docetaxel through an IV. It includes regular doctor visits, blood tests, and possibly tumor biopsies. Alternative treatments may include other chemotherapy, targeted therapies, or immunotherapy, depending on the specific cancer type and prior treatments. The trial aims to enroll 329 participants.

Official Summary

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 Anvumetostat 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 Anvumetostat in adult participants with metastatic or locally advanced MTAP-null solid tumors.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 and older with advanced solid tumors that have a specific genetic marker (MTAP-null) or loss of MTAP expression. Patients must have tumors that can be measured and be in good general health (ECOG 0-1). Individuals with spinal cord compression, untreated brain metastases, or active serious infections cannot join. Those who have had certain prior cancer treatments or have specific heart or lung conditions may also be excluded. This trial is studying Advanced MTAP-null Solid Tumors, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures will determine how safe the drug is, what the best dose is, and how well it works by looking at tumor shrinkage and how long patients live without their cancer getting wor The specific primary outcome measures are: Parts 1 and 2: Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) (28 days); Parts 1 and 2: Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) (Up to approximately 3 years); Part 3: Objective Response Rate (ORR) (Up to approximately 3 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 advanced solid tumors with a specific genetic alteration (MTAP-null), for which limited effective options currently exist. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Advanced MTAP-null Solid Tumors, where improved treatment options are needed.

Investor Insight

This trial targets a niche but potentially significant patient population with MTAP-null solid tumors, an area with unmet medical need, suggesting potential for a targeted therapy if efficacy is demon 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 type of solid tumor being studied and if your tumor has the MTAP-null marker. Understand the potential side effects of both Anvumetostat and docetaxel, and how they will be managed. Be prepared for regular clinic visits, blood draws, and potentially imaging scans to monitor your response to 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: 329 participants

Interventions

• DRUG: Anvumetostat — Anvumetostat: Orally via tablet
• DRUG: Docetaxel — Docetaxel: Intravenous infusion
• DRUG: Comparator Anvumetostat Test Tablet — Comparator Anvumetostat test tablet: Orally via tablet. Only participants in the DSPS group of the Part 1a, Phase 1: Anvumetostat Monotherapy Dose Exploration, and Part 1j, Phase 1 arms will receive comparator Anvumetostat test tablet.

Primary Outcomes

• Parts 1 and 2: Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) (28 days)
• Parts 1 and 2: Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) (Up to approximately 3 years)
• Part 3: Objective Response Rate (ORR) (Up to approximately 3 years)

Secondary Outcomes

• Parts 1 and 2: Maximal Plasma Concentration (Cmax) of Anvumetostat (Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Part 1 Cycle = 28 days, Part 2 Cycle =21 days))
• Parts 1 and 2: Time to Achieve Maximal Plasma Concentration (Tmax) of Anvumetostat (Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Part 1 Cycle = 28 days, Part 2 Cycle =21 days))
• Parts 1 and 2: Area Under the Plasma Concentration Versus Time Curve (AUC) of Anvumetostat (Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Part 1 Cycle = 28 days, Part 2 Cycle =21 days))
• Part 2 Only: Maximal Plasma Concentration (Cmax) of Docetaxel (Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Cycle =21 days))
• Part 2 Only: Time to Achieve Maximal Plasma Concentration (Tmax) of Docetaxel (Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Cycle =21 days))

Full Eligibility Criteria

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)

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.
* 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

Trial Locations

• City of Hope National Medical Center, Duarte, California, United States
• California Research Institute, Glendale, California, United States
• Fomat Medical Research, Oxnard, California, United States
• University of California at SF, San Francisco, California, United States
• D and H Cancer Research Center, Margate, Florida, United States
• Boca Raton Clinical Research Medical Center Inc, Tamarac, Florida, United States
• Goshen Health Systems, Goshen, Indiana, United States
• Indiana University, Indianapolis, Indiana, United States
• Community Health Network MD Anderson Cancer Center - North, Indianapolis, Indiana, United States
• University of Maryland Medical Center, Baltimore, Maryland, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Solid Tumors
• Oncology
• Cancer
• Metastatic Cancer
• Advanced Cancer
• Genomic Medicine
• Targeted Therapy
• Chemotherapy
• Drug Development
• Clinical Trials

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