AMG 193 for Non-Small Cell Lung Cancer

Recruiting at 111 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Amgen

Disqualifiers: EGFR, ALK, ROS1, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called AMG 193, an experimental drug for non-small cell lung cancer (NSCLC). The study aims to determine the safety and effectiveness of two different doses of AMG 193. Participants take the medication orally once a day in 28-day cycles. This trial may suit individuals with advanced NSCLC who have a specific genetic feature (MTAP deletion) and have tried at least one other treatment. Participants should not have certain genetic mutations treatable with other targeted therapies. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that AMG 193 is likely to be safe for humans?

Research has shown that AMG 193 was safe in earlier studies. It did not cause major problems with blood cell production, indicating it was generally well-tolerated by patients. AMG 193 targets specific cancer cells while sparing normal cells, reducing side effects. Although more information is always useful, these findings suggest that AMG 193 is relatively safe for humans based on current evidence. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about AMG 193 for non-small cell lung cancer because it introduces a novel approach that sets it apart from traditional treatments like chemotherapy, surgery, and radiation. Unlike these standard options, which primarily target rapidly dividing cells, AMG 193 works by inhibiting PRMT5, an enzyme that plays a crucial role in cancer cell growth. This targeted mechanism offers the potential for more precise treatment with fewer side effects, making it a promising option for patients who might not respond well to existing therapies. Additionally, AMG 193 is administered orally, providing a more convenient option compared to intravenous treatments.

What evidence suggests that AMG 193 might be an effective treatment for non-small cell lung cancer?

Research has shown that AMG 193 may help treat certain cancers, particularly those with specific genetic changes called MTAP deletions. Studies have found that AMG 193 can slow the growth of these cancer cells by targeting a protein called PRMT5, without affecting normal cells. In earlier studies, patients reported that the treatment helped shrink or slow down their tumors. Additionally, AMG 193 did not cause serious side effects, such as major drops in blood cell counts, indicating its safety. Overall, evidence suggests that AMG 193 could be effective in treating non-small cell lung cancer with these specific genetic features. Participants in this trial will receive AMG 193 in different dosing regimens to further evaluate its effectiveness and safety. ^{1 2 3 4 5}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

This trial is for adults with advanced non-small cell lung cancer (NSCLC) that lacks a gene called MTAP. Participants should have tried at least one treatment before, can live more than 3 months, and may have small, stable brain tumors not needing steroids. They must provide tissue samples from previous biopsies.

Inclusion Criteria

My lung cancer cannot be removed by surgery and lacks the MTAP gene.

My cancer returned or worsened after at least one treatment for advanced disease.

I have a tissue sample or block from a previous procedure available.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Evaluation

Participants will be randomized to receive one of 2 active dose levels of AMG 193 orally daily in 28-day cycles to determine the recommended phase 2 dose

28 days

Dose Expansion

Participants will receive AMG 193 at the recommended phase 2 dose in 28-day cycles

28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AMG 193

Trial Overview The study tests two different doses of AMG 193 to see how safe and effective they are against NSCLC. The drug's performance will be assessed by the researchers and also independently reviewed without knowing which dose was given.

How Is the Trial Designed?

Group I: Part 2: Dose Expansion Experimental Treatment 1 Intervention

Participants will receive AMG 193 PO QD in 28-day cycles at the RP2D.

Group II: Part 1: Dose Evaluation Experimental Treatment 1 Intervention

Participants will be randomized to receive one of 2 active dose levels of AMG 193 orally (PO) daily (QD) in 28 days cycles. Part 1 of the study will determine the recommended phase 2 dose (RP2D).

Who Is Running the Clinical Trial?

Amgen

Lead Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Published Research Related to This Trial

Two FDA and EMA-approved drugs, Candesartan cilexetil and Cloperastine hydrochloride, were identified as effective inhibitors of PRMT5, a target linked to various cancers, suggesting they could be repurposed for cancer therapy.

Both drugs demonstrated significant anti-tumor effects in vitro and reduced tumor growth in vivo, indicating their potential as safe and effective treatments for cancers associated with PRMT5 overexpression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of PRMT5 by market drugs as a novel cancer therapeutic avenue. Prabhu, L., Martin, M., Chen, L., et al.[2023]

MTAP deletion in malignant pleural mesothelioma (MPM) is associated with a poor prognosis, highlighting the importance of targeting this cellular dependency.

The antibiotic Quinacrine effectively suppresses PRMT5 transcription in MTAP-deleted cells, leading to reduced cancer cell growth, suggesting a potential therapeutic strategy for treating MPM by exploiting this specific vulnerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcriptional perturbation of protein arginine methyltransferase-5 exhibits MTAP-selective oncosuppression. Busacca, S., Zhang, Q., Sharkey, A., et al.[2022]

MRTX1719 is a newly discovered drug that specifically targets the PRMT5•MTA complex, showing potent inhibition of PRMT5 activity in cancer cells lacking the MTAP gene, which is crucial for certain cancer treatments.

In mouse models with tumors, daily oral administration of MRTX1719 led to a dose-dependent reduction in PRMT5 activity and demonstrated significant antitumor effects, highlighting its potential as a targeted therapy for MTAP-deleted cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fragment-Based Discovery of MRTX1719, a Synthetic Lethal Inhibitor of the PRMT5•MTA Complex for the Treatment of MTAP-Deleted Cancers. Smith, CR., Aranda, R., Bobinski, TP., et al.[2022]

Compound 17 is a novel small-molecule inhibitor that specifically disrupts the interaction between PRMT5 and its cofactor MEP50, which is crucial for PRMT5's function in cancer cells.

In vitro studies show that compound 17 effectively inhibits PRMT5 activity in prostate and lung cancer cells with an IC50 of less than 500 nM, suggesting it could be a promising therapeutic strategy for targeting PRMT5 in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery and Biological Characterization of PRMT5:MEP50 Protein-Protein Interaction Inhibitors. Asberry, AM., Cai, X., Deng, X., et al.[2022]

PRMT5 is highly expressed in lung cancer cells but not in benign lung tissues, indicating its potential role as a biomarker for lung cancer.

Silencing PRMT5 significantly inhibited the growth of lung adenocarcinoma cells in culture and in mouse models, suggesting that targeting PRMT5 could be a promising strategy for lung cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protein arginine methyltransferase 5 is essential for growth of lung cancer cells. Gu, Z., Gao, S., Zhang, F., et al.[2021]

JNJ-64619178 is a novel and selective inhibitor of PRMT5 that shows strong potential in treating various cancers, including advanced solid tumors and non-Hodgkin's lymphoma, by effectively inhibiting tumor growth in preclinical models.

The drug demonstrated a unique mechanism of action, with increased sensitivity observed in cancer samples with splicing factor mutations, suggesting it may be particularly effective for certain patient populations with aberrant PRMT5 activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery and Pharmacological Characterization of JNJ-64619178, a Novel Small-Molecule Inhibitor of PRMT5 with Potent Antitumor Activity. Brehmer, D., Beke, L., Wu, T., et al.[2023]

In a phase I trial involving 39 patients with advanced solid tumors lacking the MTAP gene, the PRMT5 inhibitor AMG 193 showed promising results, with five patients experiencing partial responses.

These partial responses were observed across various tumor types, including esophageal, pancreatic, renal cell, gallbladder, and ovarian Sertoli-Leydig cell cancers, indicating the potential efficacy of AMG 193 in treating these specific cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AMG 193 Effective in Multiple Tumor Types. [2023]

Citations

1. annalsofoncology.org annalsofoncology.org/article/S0923-7534%2824%2903919-X/fulltext

First-in-human study of AMG 193, an MTA-cooperative ... Here, we report results of the completed monotherapy dose exploration evaluating AMG 193 in patients with MTAP-deleted solid tumors.

2. aacrjournals.org aacrjournals.org/cancerdiscovery/article/15/1/139/750846/AMG-193-a-Clinical-Stage-MTA-Cooperative-PRMT5

AMG 193, a Clinical Stage MTA-Cooperative PRMT5 Inhibitor ... AMG 193 preferentially inhibits the growth of MTAP-deleted tumor cells by inhibiting PRMT5 when in complex with MTA, thus sparing MTAP wild-type normal cells.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05094336

NCT05094336 | A Study of AMG 193 in Participants With ... The primary objective of Part 3 of this study is to evaluate the efficacy of AMG 193 in adult participants with metastatic or locally advanced MTAP-null solid ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S092375342403919X

First-in-human study of AMG 193, an MTA-cooperative ... AMG 193 demonstrated a favorable safety profile without clinically significant myelosuppression. Encouraging antitumor activity across a variety of MTAP- ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39293516/

First-in-human study of AMG 193, an MTA-cooperative ... AMG 193 demonstrated a favorable safety profile without clinically significant myelosuppression. Encouraging antitumor activity across a ...