AMG 305 for Solid Tumors

Recruiting at 32 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Amgen

Must not be taking: Immunotherapies, Monoclonal antibodies

Disqualifiers: CNS metastases, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

220 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment, AMG 305, for individuals with certain solid tumors. The main goal is to determine the safety of AMG 305 and identify the best dose for future studies. Participants will initially receive varying doses to find the optimal one, after which those with selected tumors will receive the identified dose. This trial suits individuals with solid tumors who have exhausted all standard treatment options or for whom those options are unsuitable. As a Phase 1 trial, this research focuses on understanding how AMG 305 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial requires that you stop anticancer therapies, including chemotherapy and certain targeted treatments, at least 4 weeks before starting the study treatment. Immunotherapies must be stopped 3 weeks before. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

Is there any evidence suggesting that AMG 305 is likely to be safe for humans?

Research has shown that AMG 305 targets specific proteins on cancer cells, aiming to attack cancer cells while mostly sparing healthy ones. Early studies suggest this method helps the body's immune system combat cancer.

AMG 305 is currently in phase 1 trials, marking its first testing in humans. The primary goal is to assess its safety and determine the maximum dose that can be administered without causing serious issues. Although detailed safety data from humans is not yet available, these early trials are designed to monitor side effects closely and ensure the treatment's safety. Specific information on side effects or patient reactions to AMG 305 is not yet available, but this phase aims to uncover those safety details. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

AMG 305 is unique because it targets specific pathways in solid tumors that current treatments might not address. Unlike traditional chemotherapy, which attacks rapidly dividing cells in general, AMG 305 is designed to home in on particular molecular targets within the tumor. This precision could potentially lead to fewer side effects and improved effectiveness. Researchers are excited about AMG 305 because it represents a new approach that might offer hope for patients with tumors that are resistant to existing therapies.

What evidence suggests that AMG 305 might be an effective treatment for solid tumors?

Research has shown that AMG 305, administered to participants in this trial, targets cancer cells more precisely by focusing on proteins called CDH3 and MSLN. These proteins appear on tumor cells but not on normal cells. This method aims to enhance treatment effectiveness while minimizing harm to healthy cells. Early studies demonstrated that AMG 305 successfully attaches to these proteins in tumors. Additionally, it helps the body's immune T-cells attack cancer cells. These initial findings suggest that AMG 305 could be a promising treatment for solid tumors. ^{2 4 6 7 8}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

Adults over 18 with certain solid tumors (like colorectal, lung, pancreatic cancers) who've tried all standard treatments or can't have them. They must be relatively healthy (ECOG 0-1), have a life expectancy over 3 months, and not be pregnant or breastfeeding. Excluded are those with active infections, lung disease, hepatitis B/C, HIV, autoimmune disorders needing steroids/immunosuppressants, recent major surgery or vaccine; also if they're on other trials.

Inclusion Criteria

Life expectancy > 3 months

I have a solid tumor cancer and have tried all standard treatments or cannot undergo them.

Participant has provided informed consent prior to initiation of any pre-screening study specific activities/procedures

Exclusion Criteria

I have not received any live vaccines in the last 28 days or more.

I have had cancer other than my current diagnosis in the last 2 years.

I frequently need procedures to remove excess fluid from my chest or abdomen.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Exploration

Participants will receive escalating doses of AMG 305 to determine the optimal biologically active dose

Variable duration until dose determination

Dose Expansion

Participants with specific types of cancer will receive the recommended phase 2 dose identified in Part A

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• AMG 305

Trial Overview The trial is testing AMG 305's safety and what dose works best without being too much for people with advanced solid tumors. It aims to find the highest dose patients can take without serious side effects (MTD) and decide the right amount for future studies (RP2D).

How Is the Trial Designed?

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

Participants with selected solid tumors will receive the RP2D identified in Part A.

Group II: Part A: Dose Exploration Experimental Treatment 1 Intervention

Participants will receive escalating doses of AMG 305.

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

Gemtuzumab ozogamicin, the first antibody-drug conjugate approved for CD33-positive acute myeloid leukemia (AML), was initially withdrawn from the market due to lack of clinical benefit, but later studies with new dosing regimens demonstrated its efficacy.

Pharmacokinetic modeling revealed significant relationships between drug exposure and clinical outcomes, leading to its full FDA approval in 2017 for both newly diagnosed and relapsed AML in adults and children aged 2-17 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic/Pharmacodynamic Modeling to Support the Re-approval of Gemtuzumab Ozogamicin. Fostvedt, LK., Hibma, JE., Masters, JC., et al.[2020]

AMG 176 is the first selective MCL1 inhibitor studied in humans, showing the ability to induce rapid apoptosis in certain hematologic cancer cell lines and patient samples, indicating its potential as an effective cancer treatment.

The combination of AMG 176 with venetoclax demonstrated synergistic effects in acute myeloid leukemia (AML) models, suggesting that this combination therapy could enhance treatment efficacy while remaining within tolerated doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AMG 176, a Selective MCL1 Inhibitor, Is Effective in Hematologic Cancer Models Alone and in Combination with Established Therapies. Caenepeel, S., Brown, SP., Belmontes, B., et al.[2019]

AMG 330, a bispecific T-cell engaging antibody, shows potent cytotoxic effects against CD33+ leukemic cells in vitro, with its effectiveness significantly correlated to the presence of autologous T-cells rather than solely CD33 expression levels.

The study found that AMG 330 was more effective in newly diagnosed acute myeloid leukemia (AML) patients compared to those with relapsed/refractory disease, indicating its potential as a promising treatment option across various stages of AML, while also suggesting the existence of CD33-independent resistance mechanisms in some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Broad Anti-AML Activity of the CD33/CD3 BiTE Antibody Construct, AMG 330, Is Impacted by Disease Stage and Risk. Harrington, KH., Gudgeon, CJ., Laszlo, GS., et al.[2019]

The small-molecule BH3-mimetic ABT-737 significantly enhances the effectiveness of daunorubicin (DNR) in treating acute myeloid leukemia (AML) cell lines, showing lower IC50 values when used in combination, indicating a synergistic effect.

The combination treatment not only increased cell death through enhanced apoptosis but also provided greater growth inhibition compared to using DNR alone, suggesting a potential strategy to overcome chemoresistance in leukemia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ABT-737, Synergistically Enhances Daunorubicin-Mediated Apoptosis in Acute Myeloid Leukemia Cell Lines. Dariushnejad, H., Zarghami, N., Rahmati, M., et al.[2021]

The novel radioimmunoconjugate 90Y-DOTA-peptide-ChL6 demonstrated a high therapeutic index in treating human breast cancer tumors in mice, achieving a 79% response rate at the maximum tolerated dose (MTD) of 9.6 MBq.

The treatment led to evidence of apoptosis in tumors, even in cases with mutant p53 genes, suggesting that this mechanism could be significant for future therapies targeting lethal breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Yttrium-90-DOTA-peptide-chimeric L6 radioimmunoconjugate: efficacy and toxicity in mice bearing p53 mutant human breast cancer xenografts. DeNardo, SJ., Kukis, DL., Miers, LA., et al.[2013]

Citations

1. clinicaltrials.med.nyu.edu clinicaltrials.med.nyu.edu/clinicaltrial/2364/phase-1-first-in-human-study/

Phase 1 First-In-Human Study to Explore the ... - Clinical Trials AMG 305 is designed to increase the therapeutic index in solid tumors by preferentially targeting tumor cells that co-express CDH3 and MSLN over normal cells.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8612194/

Mesothelin/CD3 Half-Life–Extended Bispecific T-Cell ... This biodistribution study with a 89 Zr-labeled mesothelin-targeted HLE BiTE molecule and a 89 Zr-control HLE BiTE molecule revealed specific tumor uptake.

3. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/anti-cdh3-msln-bite-antibody-amg-305?pn=1

Clinical Trials Using Anti-CDH3/MSLN BiTE Antibody AMG ... Review the clinical trials studying anti-cdh3/msln bite antibody amg 305 on this list and use the filters to refine the results by age and location.

4. oncologypipeline.com oncologypipeline.com/apexonco/reality-bites-again-amgen

Reality Bites again for Amgen | ApexOnco This project is AMG 305, a dual-acting Bite ... Note: *all Bites additionally hit CD3, as a means of T-cell engagement; HLE=half-life extension.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11512917/

Clinical Progresses and Challenges of Bispecific ... Bispecific antibodies have emerged as a promising therapeutic approach in the treatment of solid tumors due to their ability to simultaneously engage two ...

6. adooq.com adooq.com/amg-305.html

AMG-305 AMG 305 represents an innovative dual-targeting BiTE (bispecific T-cell engager) molecule, specifically engineered with a half-life extended (HLE) format.

7. cancer.gov cancer.gov/publications/dictionaries/cancer-drug/def/anti-cdh3-msln-bite-antibody-amg-305

Definition of anti-CDH3/MSLN BiTE antibody AMG 305 Upon administration, anti-CDH3/MSLN BiTE antibody AMG 305 binds with specificity to tumor cells co-expressing CDH3 and MSLN antigens and CD3 on cytotoxic T- ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11696039/

10 years of BiTE immunotherapy: an overview with a focus ... Alternatively, Amgen is developing half-life extended (HLE) BiTE molecules ... Importantly, data provides evidence of BiTE monotherapy efficacy in solid tumors ( ...