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AMG 410 Alone and in Combination With Other Agents in Participants With KRAS Altered Advanced or Metastatic Solid Tumors

PHASE1RECRUITING

The purpose of this first-in-human study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of AMG 410 when administered alone or in combination with other agents in participants with advanced or metastatic solid tumors harboring KRAS alterations. This is a dose-escalation study in which participants will be assigned to multiple dose levels (DLs) of AMG 410, either as monotherapy or in combination with other agents, followed by expansion cohorts. The goal is to determine the Maximum Tolerated Dose (MTD)-the highest dose with acceptable safety and manageable side effects-or the Recommended Phase 2 Dose (RP2D) of AMG 410 in adult participants with KRAS-altered advanced or metastatic solid tumors.

Study details:

This is a multicenter, multinational, open-label Phase 1/1b study designed to evaluate the safety, tolerability, PK, PD, and preliminary antitumor activity of AMG 410 in adult participants with advanced or metastatic solid tumors characterized by KRAS alterations. The study will begin with a dose-escalation phase, during which AMG 410 will be administered orally, either as monotherapy or in combination with other agents. Dose escalation will follow a model-based approach to identify the MTD or RP2D.

Following dose escalation, additional expansion cohorts may be enrolled at selected dose levels to further characterize the safety profile, PK/PD relationships, and preliminary efficacy in specific tumor types or molecular subgroups. Participants will continue treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-defined discontinuation criteria. The maximum duration of AMG 410 administration in this study is 3 years.

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

  1. Age ≥ 18 years (or > legal age within the country if it is older than 18 years).
  2. Pathologically documented, locally-advanced or metastatic malignancy with any missense mutation in the KRAS gene or evidence of KRAS amplification using an analytically validated KRASWT amplification assay.
  3. Participants must have no standard of care treatment options or have actively refused such therapy.
  4. Able to swallow and retain per oral administered study treatment.
  5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  6. Disease measurable as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), as determined by the site investigator.
  7. Adequate organ function.
  8. Archival (formalin-fixed, paraffin-embedded [FFPE]) tumor tissue or block collected within 5 years before screening must be available. Participants without archived tumor tissue may undergo tumor biopsy before AMG 410 dosing (Day1).

Exclusion criteria

  1. Untreated symptomatic central nervous system or leptomeningeal metastases.
  2. Uncontrolled pleural effusion and/or ascites.
  3. History of other malignancy within the past 5 years.
  4. Active systemic infection or symptoms that indicate an acute and/or uncontrolled infection requiring IV antibiotics within 7days prior to the first dose of study treatment.
  5. History of arterial or venous thrombosis (eg, stroke, transient ischemic attack, pulmonary embolism, or deep vein thrombosis).
  6. Live and live-attenuated vaccines are prohibited within 28 days prior to the first dose of study treatment.
  7. History of solid organ transplant.
  8. Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, hormonal therapy, or investigational agent) within 28 days of first dose of study treatment.
  9. Presence or history of any of the following viral infections: HIV, Hepatitis C, Hepatitis B, and active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
  10. Toxicities from prior anti-tumor therapy (including radiotherapy) not having improved to at least Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 1.
  11. Therapeutic or palliative radiation therapy within 2 weeks of first dose of study treatment.
  12. Major surgery within 28 days of first dose of study treatment.
  13. History or evidence of any other clinically significant disorder, condition, or disease that, in the opinion of the investigator, would pose a risk to participant safety.

Eligibility

Age eligible for study : NA

Healthy volunteers accepted : No

Gender eligible for study: ALL

Things to know

Study dates

Study start:

Primary completion:

Study completion finish:

study type

Study type

TREATMENT

phase

Phase

    PHASE1

trial

Study ID

NCT07094113

Intervention or treatment

DRUG: AMG 410

DRUG: Pembrolizumab

DRUG: Panitumumab

Conditions

  • KRAS Altered Advanced or Metastatic Solid Tumors

  • Condition: KRAS Altered Advanced or Metastatic Solid Tumors

  • DRUG: AMG 410 and other drugs

  • Parkville, Victoria, Australia

  • Sponsor: Amgen

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Are you running this trial?

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Research sites nearby

Closest Location:

Peter MacCallum Cancer Centre

Select from list below to view details:

  • Peter MacCallum Cancer Centre

    Parkville, Victoria, Australia

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Who is running the clinical trial?

A

Amgen

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/ArmIntervention/Treatment
EXPERIMENTAL: Part 1: Monotherapy Dose Exploration
  • Participants will receive escalating doses of AMG 410.
Drug: AMG 410
    EXPERIMENTAL: Part 1: Food Effect Substudy Cohort
    • A food effect substudy will be conducted. During the substudy, participants will receive AMG 410 under fasted and fed conditions.
    Drug: AMG 410
      EXPERIMENTAL: Part 1: China-specific Cohort
      • Participants identified through regionally approved molecular KRAS testing will receive AMG 410.
      Drug: AMG 410
        EXPERIMENTAL: Part 2: Monotherapy Dose Expansion
        • Monotherapy dose expansion of AMG 410 may proceed in KRAS altered tumors in non-small cell lung cancer (NSCLC), colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), and other KRAS altered tumor types.
        Drug: AMG 410
          EXPERIMENTAL: Part 3a: Combination Therapy Dose Exploration and Dose Expansion
          • Part 3a allows for AMG 410 dose exploration and expansion in combination with pembrolizumab in KRAS altered advanced or metastatic solid tumors.
          Drug: AMG 410, Drug: Pembrolizumab
            EXPERIMENTAL: Part 3b: Combination Therapy Dose Exploration and Dose Expansion
            • Part 3b allows for AMG 410 dose exploration and expansion in combination with panitumumab in advanced or metastatic CRC and/or PDAC.
            Drug: AMG 410, Drug: Panitumumab

              What is the study measuring?

              Primary Outcome

              MeasureDescriptionTime Frame
              Number of Participants with Dose Limiting Toxicities (DLTs)Not SpecifiedUp to 28 days
              Number of Participants with Treatment Emergent Adverse Events (TEAEs)Clinically significant changes in safety assessments (vital signs, electrocardiograms \[ECGs\], and clinical laboratory tests) are to be reported as adverse events.Up to approximately 3 years
              Number of Participants with Serious Adverse Events (SAEs)Clinically significant changes in safety assessments (vital signs, ECGs, and clinical laboratory tests) are to be reported as adverse events.Up to approximately 3 years

              Secondary Outcome

              MeasureDescriptionTime Frame
              Maximum Concentration (Cmax) of AMG 410Not SpecifiedUp to 85 days
              Time to Reach Cmax (Tmax) of AMG 410Not SpecifiedUp to 85 days
              Area Under the Concentration-time Curve (AUC) Over the Dosing Interval of AMG 410Not SpecifiedUp to 85 days
              Confirmed Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1Not SpecifiedUp to approximately 3 years
              Clinical Benefit per RECIST v1.1Not SpecifiedUp to approximately 3 years
              Duration of Response (DoR) per RECIST v1.1Not SpecifiedUp to approximately 3 years
              Time to Response (TTR) per RECIST v1.1Not SpecifiedUp to approximately 3 years
              Progression-free Survival (PFS) per RECIST v1.1Not SpecifiedUp to approximately 3 years
              Overall Survival (OS)Not SpecifiedUp to approximately 3 years
              Food Effect Substudy Cohort: Cmax of AMG 410 in the Fed and/or Fasted StateNot SpecifiedUp to 24 days
              Food Effect Substudy Cohort: Tmax of AMG 410 in the Fed and/or Fasted StateNot SpecifiedUp to 24 days
              Food Effect Substudy Cohort: AUC Over the Dosing Interval of AMG 410 in the Fed and/or Fasted StateNot SpecifiedUp to 24 days
              Change From Baseline in Tumor Phosphorylated Extracellular Signal Regulated Kinase (pERK)Not SpecifiedBaseline up to approximately 3 years
              Are you running this trial?If you're a clinic or sponsor, you can claim this study.
              Claim this trial

              References

              Clinical Trials Gov: AMG 410 Alone and in Combination With Other Agents in Participants With KRAS Altered Advanced or Metastatic Solid Tumors

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