AMG 994 + AMG 404 for Cancer

No longer recruiting at 19 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Amgen

Must not be taking: Checkpoint inhibitors, Immunosuppressive corticosteroids

Disqualifiers: Primary brain tumor, Recent malignancy, Organ transplant, Active infection, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 1988

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, AMG 994, both alone and with another drug, AMG 404, to assess safety and tolerance. The focus is on individuals with advanced solid tumors, such as mesothelioma or pancreatic cancer, that have not responded to other treatments. Participants should have tumors expressing a specific protein called MSLN and must be prepared to undergo a biopsy before and during the trial. The study aims to identify the best dose for future research. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have had anti-tumor therapy within 21 days, a checkpoint inhibitor within 9 weeks, or live vaccine therapy within 4 weeks before starting the study. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that AMG 994, when combined with AMG 404, is being tested to determine the safest dose for individuals with advanced solid tumors. Earlier studies found that AMG 404 alone was safe at the doses tested, with some patients showing positive responses in various tumor types. This indicates that the treatment did not cause severe side effects in earlier tests and showed potential in fighting cancer.

As this is a phase 1 trial, the primary goal is to establish the safe dosage of the drug. This phase typically marks the first time the treatment is tested in humans, so safety information is still being collected. Participants should understand that there may be unknown risks, as this is an early stage of testing. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about AMG 994 and its combination with AMG 404 because these treatments bring a fresh approach to battling advanced solid tumors. Unlike traditional therapies that may target the tumor more broadly, AMG 994 works by targeting specific proteins involved in tumor growth, potentially offering a more precise attack on cancer cells. This targeted mechanism could lead to fewer side effects and better outcomes for patients. Additionally, the combination with AMG 404 aims to enhance the immune system's ability to fight cancer, offering a dual approach to treatment that is not typically seen with conventional therapies.

What evidence suggests that AMG 994 and AMG 404 could be effective for advanced solid tumors?

Research has shown that AMG 404, when used alone, is generally well tolerated by patients with advanced solid tumors. No serious side effects prevented dose escalation at various levels. This trial tests AMG 994 in combination with AMG 404 to determine the safest and most effective dose combination. This combination aims to block the pathways cancer cells use for growth. Early studies are investigating whether this combination can improve outcomes for patients with advanced cancers. ^{1 2 3 6 7}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

Inclusion Criteria

Hepatic function, as follows: Total bilirubin (TBL) ≤ 1.5 x upper limit of normal (ULN) or ≤ 3 x ULN for participants with liver metastasis Aspartate transaminase (AST) ≤ 3 x ULN or ≤ 5 x ULN for participants with liver metastasis Alanine aminotransferase (ALT) ≤ 3 x ULN or ≤ 5 x ULN for participants with liver metastasis Alkaline phosphatase ≤ 2.5 x ULN or ≤ 5 x ULN for participants with liver metastasis

- Standard systemic therapy has failed or is not available.

Life expectancy of > 3 months, in the opinion of the investigator.

Exclusion Criteria

Prior/Concomitant Therapy

Other Exclusions

-- Participants with NSCLC squamous cell carcinoma (Part 1), MSLN negative NSCLC squamous cell carcinoma (Part 2), or MSLN negative NSCLC adenocarcinoma (Part 2) once the participant has been screened for MSLN expression.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Exploration

Determine the maximum tolerated dose (MTD) or the recommended phase 2 dose (RP2D) of AMG 994, in combination with AMG 404

Up to Day 28 of Cycle 1 (one cycle = 28 days)

Weekly visits for AMG 994, every 4 weeks for AMG 404

Dose Expansion

Participants will be administered with the MTD or RP2D of AMG 994 identified in the dose escalation part of the study, in combination with AMG 404

Up to approximately 19.32 months

Weekly visits for AMG 994, every 4 weeks for AMG 404

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 140 days after last dose

What Are the Treatments Tested in This Trial?

Interventions

• AMG 404
• AMG 994

How Is the Trial Designed?

Group I: Part 2: Dose Expansion Experimental Treatment 2 Interventions

Participants will be administered with the MTD or RP2D of AMG 994 identified in the dose escalation part of the study, in combination with AMG 404.

Group II: Part 1c: Dose Exploration Experimental Treatment 2 Interventions

Determine the maximum tolerated dose (MTD) or the recommended phase 2 dose (RP2D) of AMG 994, in combination with AMG 404.

Group III: Part 1b: Dose Exploration Experimental Treatment 2 Interventions

Determine the maximum tolerated dose (MTD) or the recommended phase 2 dose (RP2D) of AMG 994, in combination with AMG 404.

Group IV: Part 1a: Dose Exploration Experimental Treatment 2 Interventions

Determine the maximum tolerated dose (MTD) or the recommended phase 2 dose (RP2D) of AMG 994, in combination with AMG 404.

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

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04727554

NCT04727554 | Study of AMG 994 Monotherapy and ... AMG 994 will be administered by short term intravenous (IV) infusion once weekly in each 28-day cycle and AMG 404 will be administered by short-term IV infusion ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04727554?tab=history&a=17

Record History | ver. 17: 2022-11-16 | NCT04727554 Study of AMG 994 Monotherapy and AMG 994 and AMG 404 Combination Therapy in Participants With Advanced Solid Tumors. ClinicalTrials.gov ID NCT04727554.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12049887/

A phase I, open-label, multicentre, first-in-human study to ... AMG 404 monotherapy at doses of 240 mg, 480 mg and 1050 mg Q4W showed no DLTs and was generally well tolerated in patients with advanced solid ...

4. withpower.com withpower.com/trial/phase-1-neoplasms-3-2021-95310

Study of AMG 994 Monotherapy and ... This trial tests two experimental drugs, AMG 994 and AMG 404, in patients with advanced cancer. The goal is to find the safest dose and see how well patients ...

5. adisinsight.springer.com adisinsight.springer.com/trials/700333145

A Phase 1, Multicenter, Open-label, Dose Exploration and ... ... Efficacy of AMG 994 Monotherapy and Combination of AMG 994 and AMG 404 in Subjects With Advanced Solid Tumors. Status: Completed. Phase of Trial: Phase I.

6. veri.larvol.com veri.larvol.com/news/amg-404/drug

News - zeluvalimab (AMG 404) AMG 404 monotherapy was tolerable at the tested doses, with encouraging antitumour activity observed across tumour types. 5 months ago. P1 data • PK/PD data • ...

7. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2019-0011.html

A Phase 1 Study to Evaluate Safety, Tolerability, ... To evaluate the safety and tolerability of AMG 404, a monoclonal antibody that binds to PD-1 and inhibits its engagement with ligands, in patients with advanced ...