AMG 305 for Solid Tumors

Recruiting at25 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Amgen

Must not be taking: Immunotherapies, Monoclonal antibodies

Disqualifiers: CNS metastases, HIV, Hepatitis, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called AMG 305 in adults to see if it is safe and how well people can tolerate it. Researchers will start with a low dose and gradually increase it to find the best amount that works without causing too many side effects.

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.

What makes the drug AMG 305 unique for treating solid tumors?

AMG 305 is a novel treatment that uses a bispecific T-cell engager (BiTE) approach, which means it can simultaneously bind to two different targets, potentially enhancing the immune system's ability to attack cancer cells. This mechanism is different from traditional chemotherapy or single-target therapies, offering a new way to treat solid tumors. ^{1 2 3 4 5}

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• AMG 305 (Monoclonal Antibodies)

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).

Participant Groups

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

Participants with non-small cell lung cancer (NSCLC), colorectal cancer (CRC), pancreatic cancer, and other 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

Findings from Research

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]

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]

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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

AMG 176, a Selective MCL1 Inhibitor, Is Effective in Hematologic Cancer Models Alone and in Combination with Established Therapies. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Pharmacokinetic/Pharmacodynamic Modeling to Support the Re-approval of Gemtuzumab Ozogamicin. [2020]

3. Iran pubmed.ncbi.nlm.nih.gov

ABT-737, Synergistically Enhances Daunorubicin-Mediated Apoptosis in Acute Myeloid Leukemia Cell Lines. [2021]

4. United States 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. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Yttrium-90-DOTA-peptide-chimeric L6 radioimmunoconjugate: efficacy and toxicity in mice bearing p53 mutant human breast cancer xenografts. [2013]