Clinical Trials /

Study of AMG 994 Monotherapy and AMG 994 and AMG 404 Combination Therapy in Participants With Advanced Solid Tumors

NCT04727554

Description:

The primary objective of this study is to evaluate the safety, tolerability, and maximum tolerated dose (MTD)/maximum tolerated combination dose (MTCD) or recommended phase 2 dose (RP2D) of AMG 994 as monotherapy and AMG 994 in combination with AMG 404 in participants with advanced solid tumors.

Related Conditions:
  • High Grade Ovarian Serous Adenocarcinoma
  • Malignant Leptomeningeal Neoplasm
  • Malignant Solid Tumor
  • Mesothelioma
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of AMG 994 Monotherapy and AMG 994 and AMG 404 Combination Therapy in Participants With Advanced Solid Tumors
  • Official Title: A Phase 1, Multicenter, Open-label, Dose Exploration and Dose Expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of AMG 994 Monotherapy and Combination of AMG 994 and AMG 404 in Subjects With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 20190136
  • NCT ID: NCT04727554

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
AMG 994Part 1a: Dose Exploration
AMG 404Part 1a: Dose Exploration

Purpose

The primary objective of this study is to evaluate the safety, tolerability, and maximum tolerated dose (MTD)/maximum tolerated combination dose (MTCD) or recommended phase 2 dose (RP2D) of AMG 994 as monotherapy and AMG 994 in combination with AMG 404 in participants with advanced solid tumors.

Trial Arms

NameTypeDescriptionInterventions
Part 1a: Dose ExplorationExperimentalDetermine the maximum tolerated dose (MTD) or the recommended phase 2 dose (RP2D) of AMG 994, in combination with AMG 404.
  • AMG 994
  • AMG 404
Part 1b: Dose ExplorationExperimentalDetermine the maximum tolerated dose (MTD) or the recommended phase 2 dose (RP2D) of AMG 994, in combination with AMG 404.
  • AMG 994
  • AMG 404
Part 1c: Dose ExplorationExperimentalDetermine the maximum tolerated dose (MTD) or the recommended phase 2 dose (RP2D) of AMG 994, in combination with AMG 404.
  • AMG 994
  • AMG 404
Part 2: Dose ExpansionExperimentalParticipants 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.
  • AMG 994
  • AMG 404

Eligibility Criteria

        Inclusion Criteria:

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

          -  Age ≥ 18 years at the time of signing informed consent.

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

          -  Participant must have histologically or cytologically proven metastatic or locally
             advanced solid tumors of known MSLN expression who have relapsed after and/or are
             refractory to established and available therapies with known clinical benefit, for
             which:

               -  No standard systemic therapy exists; or

               -  Standard systemic therapy has failed or is not available.

          -  Dose Expansion (Part 2): Participant must have one of the following malignancies:
             mesothelioma, pancreatic adenocarcinoma, MSLN positive NSCLC squamous cell carcinoma
             or adenocarcinoma, high grade serous ovarian carcinoma.

          -  At least 1 measurable or evaluable lesion as defined by modified RECIST 1.1
             guidelines.

          -  Participants must be willing to undergo a biopsy prior to enrollment and during
             treatment with AMG 994.

          -  Participants with treated brain metastases are eligible provided they meet the
             following criteria:

               -  Definitive therapy was completed at least 2 weeks prior to enrollment.

               -  No evidence of radiographic central nervous system (CNS) progression or CNS
                  disease following definitive therapy and by the time of study screening. Patients
                  manifesting progression in lesions previously treated with stereotactic
                  radiosurgery may still be eligible if pseudoprogression can be demonstrated by
                  appropriate means and after discussion with the medical monitor.

               -  Any CNS disease is asymptomatic, any neurologic symptoms due to CNS disease have
                  returned to baseline, or non-serious CNS diseases that are asymptomatic and
                  deemed irreversible (eg, peripheral neuropathy), the patient is off steroids for
                  at least 7 days (physiologic doses of steroids are permitted), and the patient is
                  off or on stable doses of anti-epileptic drugs for malignant CNS disease and has
                  not had a seizure within 1 month prior to the screening visit.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.

          -  Hematologic function, as follows (transfusions or growth factor support must not be
             administered within 7 days prior to obtaining screening labs):

               -  Absolute neutrophil count (ANC) ≥ 1.5 x 109/L

               -  Platelet count ≥ 75 x 109/L

               -  Hemoglobin ≥ 9 g/dL

          -  Adequate renal laboratory assessments, as follows:

             • Estimated glomerular filtration rate based on Modification of Diet in Renal Disease
             (MDRD) calculation ≥ 45 mL/min/1.73 m2

          -  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

        Exclusion Criteria:

        Disease Related

          -  Primary brain tumor, untreated or symptomatic brain metastases and leptomeningeal
             disease.

        Other Medical Conditions

          -  History of other malignancy within the past 2 years, with the following exception[s]:

               -  Malignancy treated with curative intent and with no known active disease present
                  for ≥ 3 years before enrollment and felt to be at low risk for recurrence by the
                  treating physician.

               -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
                  of disease.

               -  Adequately treated cervical carcinoma in situ without evidence of disease.

               -  Adequately treated breast ductal carcinoma in situ without evidence of disease.

               -  Prostatic intraepithelial neoplasia without evidence of prostate cancer.

               -  Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in
                  situ.

          -  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.

          -  Participants with sarcomatoid mesothelioma and small cell lung cancer will be excluded
             from both the Dose Exploration (Part 1) and Dose Expansion (Part 2) parts of the
             study.

          -  History of solid organ transplantation.

          -  Major surgery within 28 days of study day 1.

        Prior/Concomitant Therapy

          -  Anti-tumor therapy (radiotherapy, chemotherapy, antibody therapy, molecular targeted
             therapy, or investigational agent) within 21 days prior to study day 1.

          -  Treatment with a checkpoint inhibitor within 9 weeks prior to study day 1.

          -  Live vaccine therapy within 4 weeks prior to study drug administration.

          -  Current treatment or within 14 days of day 1 with immunosuppressive corticosteroid
             defined as > 10 mg prednisone daily or equivalent. Steroids with no minimal systemic
             effect (such as topical or inhalation) are permitted.

        Prior/Concurrent Clinical Study Experience

          -  Currently receiving treatment in another investigational device or drug study, or less
             than 21 days prior to study day 1 since ending treatment on another investigational
             device or drug study(ies).

          -  Evidence of active or radiological sequelae of non-infectious pneumonitis.

          -  History of any immune-related colitis. Infectious colitis is allowed if evidence of
             adequate treatment and clinical recovery exists and at least 3 months interval
             observed since diagnosis of colitis.

          -  History of allergic reactions or acute hypersensitivity reaction to antibody
             therapies.

          -  Positive/non-negative test results for human immunodeficiency virus (HIV).

          -  Hepatitis B and C based on the following results:

               -  Positive for hepatitis B surface antigen (HBsAg) (indicative of chronic hepatitis
                  B or recent acute hepatitis B)

               -  Negative HBsAG and positive for hepatitis B core antibody: hepatitis B virus DNA
                  by polymerase chain reaction (PCR) is necessary. Detectable hepatitis B virus DNA
                  suggests occult hepatitis B.

               -  Positive hepatitis C virus antibody (HCVAb): hepatitis C virus RNA by PCR is
                  necessary. Detectable hepatitis C virus RNA suggests chronic hepatitis C.

          -  Active infection requiring oral or intravenous therapy.

          -  Active or history of any autoimmune disease or immunodeficiencies. Participants with
             diabetes Type 1, vitiligo, psoriasis, hypo- or hyper-thyroid disease not requiring
             immunosuppressive treatment are permitted.

          -  Myocardial infarction within 6 months of study day 1, symptomatic congestive heart
             failure (New York Heart Association > class II), unstable angina, or cardiac
             arrhythmia requiring medication.

          -  Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to
             Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 1, or are
             stable and well controlled with minimal, local, or noninvasive intervention AND there
             is agreement to allow by both the investigator and the Amgen Medical Monitor.

               -  Any history of grade 3 or higher colitis, pneumonitis, or neurological toxicity
                  OR

               -  Unresolved toxicities from prior checkpoint inhibitor therapy, defined as not
                  having resolved to CTCAE v5.0 grade 1.

               -  Exception: - clinically stable hypothyroid status managed with hormone
                  replacement therapy, is permitted

        Other Exclusions

          -  Female participant is pregnant or breastfeeding or planning to become pregnant or
             breastfeed during treatment and for an additional 6 months after the last dose of AMG
             994 and/or AMG 404.

          -  Female participants of childbearing potential unwilling to use 1 highly effective
             method of contraception during treatment and for an additional 6 months after the last
             dose of AMG 994 and/or AMG 404.

          -  Female participants of childbearing potential with a positive pregnancy test assessed
             at day 1 by a serum pregnancy test.

          -  Male participants with a female partner of childbearing potential who are unwilling to
             practice sexual abstinence (refrain from heterosexual intercourse) or use
             contraception during treatment and for an additional 8 months after the last dose of
             AMG 994 and/or AMG 404.

          -  Male participants unwilling to abstain from donating sperm during treatment and for an
             additional 8 months after the last dose of AMG 994 and/or AMG 404.

          -  Participant has known sensitivity to any of the products or components to be
             administered during dosing.

          -  Participant likely to not be available to complete all protocol-required study visits
             or procedures, and/or to comply with all required study procedures to the best of the
             participant and investigator's knowledge.

          -  History or evidence of any other clinically significant disorder, condition or disease
             (with the exception of those outlined above) that, in the opinion of the investigator
             or Amgen physician, if consulted, would pose a risk to participant safety or interfere
             with the study evaluation, procedures or completion.
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with Dose Limiting Toxicities (DLTs)
Time Frame:28 days
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Objective Response (OR)
Time Frame:Up to 36 months
Safety Issue:
Description:
Measure:Duration of Response (DOR)
Time Frame:Up to 36 months
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:Up to 36 months
Safety Issue:
Description:
Measure:Progression-Free Survival (PFS)
Time Frame:Up to 36 months
Safety Issue:
Description:
Measure:Time to Progression
Time Frame:Up to 36 months
Safety Issue:
Description:
Measure:Time to Subsequent Therapy
Time Frame:Up to 36 months
Safety Issue:
Description:
Measure:Maximum Observed Serum Concentration (Cmax) of AMG 994
Time Frame:Up to 30 months
Safety Issue:
Description:
Measure:Maximum Observed Serum Concentration (Cmax) of AMG 404
Time Frame:Up to 30 months
Safety Issue:
Description:
Measure:Minimum Observed Serum Concentration (Cmin) of AMG 994
Time Frame:Up to 30 months
Safety Issue:
Description:
Measure:Minimum Observed Serum Concentration (Cmin) of AMG 404
Time Frame:Up to 30 months
Safety Issue:
Description:
Measure:Area Under the Serum Concentration-time Curve (AUC) of AMG 994
Time Frame:Up to 30 months
Safety Issue:
Description:
Measure:Area Under the Serum Concentration-time Curve (AUC) of AMG 404
Time Frame:Up to 30 months
Safety Issue:
Description:
Measure:Half-life (t1/2) of AMG 994
Time Frame:Up to 30 months
Safety Issue:
Description:
Measure:Half-life (t1/2) of AMG 404
Time Frame:Up to 30 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Amgen

Last Updated

June 17, 2021