Clinical Trials /

A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic or Inoperable Locally Advanced Triple-Negative Breast Cancer (Morpheus-TNBC)

NCT03424005

Description:

This is a Phase Ib/II, open-label, multicenter, randomized umbrella study evaluating the efficacy and safety of multiple immunotherapy-based treatment combinations in patients with metastatic or inoperable locally advanced TNBC who had disease progression during or following first-line metastatic treatment with chemotherapy. The study will be performed in two stages. During Stage 1, participants will be randomized to capecitabine (control) or an atezolizumab-containing doublet or triplet combination. Those who experience disease progression, loss of clinical benefit, or unacceptable toxicity may be eligible to receive a new doublet combination treatment in Stage 2 until loss of clinical benefit or unacceptable toxicity. New treatment arms may be added and/or existing treatment arms may be closed during the course of the study on the basis of ongoing clinical efficacy and safety as well as the current treatments available.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic Triple-Negative Breast Cancer (Morpheus-TNBC)
  • Official Title: A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating The Efficacy And Safety Of Multiple Immunotherapy-Based Treatment Combinations In Patients With Metastatic Triple-Negative Breast Cancer (Morpheus-TNBC)

Clinical Trial IDs

  • ORG STUDY ID: CO40115
  • SECONDARY ID: 2017-002038-21
  • NCT ID: NCT03424005

Conditions

  • Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
CapecitabineCapecitabine
AtezolizumabAtezolizumab + Ipatasertib
IpatasertibAtezolizumab + Ipatasertib
SGN-LIV1AAtezolizumab + SGN-LIV1A
BevacizumabAtezolizumab + Bevacizumab
CobimetinibAtezolizumab + Bevacizumab + Cobimetinib
Chemotherapy (Gemcitabine + Carboplatin or Eribulin)Atezolizumab + Chemo (Gemcitabine + Carboplatin or Eribulin)

Purpose

This is a Phase Ib/II, open-label, multicenter, randomized umbrella study evaluating the efficacy and safety of multiple immunotherapy-based treatment combinations in patients with metastatic TNBC who had disease progression during or following first-line metastatic treatment with chemotherapy. The study will be performed in two stages. During Stage 1, participants will be randomized to capecitabine (control) or an atezolizumab-containing doublet or triplet combination. Those who experience disease progression, loss of clinical benefit, or unacceptable toxicity may be eligible to receive a new doublet combination treatment in Stage 2 until loss of clinical benefit or unacceptable toxicity. New treatment arms may be added and/or existing treatment arms may be closed during the course of the study on the basis of ongoing clinical efficacy and safety as well as the current treatments available.

Trial Arms

NameTypeDescriptionInterventions
CapecitabineActive ComparatorParticipants will receive Capecitabine until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1). Participants who progressed on treatment may have the option of receiving Atezolizumab + Chemo, provided they meet the eligibility criteria
  • Capecitabine
Atezolizumab + IpatasertibExperimentalParticipants will receive doublet combination treatment with atezolizumab + Capecitabine until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Participants who progressed on treatment may have the option of receiving Atezolizumab + Chemo, provided they meet the eligibility criteria
  • Atezolizumab
  • Ipatasertib
Atezolizumab + SGN-LIV1AExperimentalParticipants will receive doublet combination treatment with atezolizumab plus SGNLIV1A until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Participants who progressed on treatment may have the option of receiving Atezolizumab + Chemo, provided they meet the eligibility criteria
  • Atezolizumab
  • SGN-LIV1A
Atezolizumab + BevacizumabExperimentalParticipants will receive doublet combination treatment with atezolizumab plus Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Participants who progressed on treatment may have the option of receiving Atezolizumab + Chemo, provided they meet the eligibility criteria
  • Atezolizumab
  • Bevacizumab
Atezolizumab + Bevacizumab + CobimetinibExperimentalParticipants will receive doublet combination treatment with atezolizumab + Bevacizumab + Cobimetinib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Participants who progressed on treatment may have the option of receiving Atezolizumab + Chemo, provided they meet the eligibility criteria
  • Atezolizumab
  • Bevacizumab
  • Cobimetinib
Atezolizumab + CapecitabineExperimentalParticipants will receive doublet combination treatment with atezolizumab + Capecitabine until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Participants who progressed on treatment may have the option of receiving Atezolizumab + Chemo, provided they meet the eligibility criteria
  • Capecitabine
  • Atezolizumab
Atezolizumab + Chemo (Gemcitabine + Carboplatin or Eribulin)ExperimentalParticipants will receive doublet combination treatment with atezolizumab plus Chemotherapy (Gemcitabine + Carboplatin or Eribulin) until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
  • Atezolizumab
  • Chemotherapy (Gemcitabine + Carboplatin or Eribulin)

Eligibility Criteria

        Inclusion Criteria Stage 1

          -  ECOG Performance Status of 0 or 1

          -  Metastatic or locally advanced, histologically documented TNBC (absence of HER2, ER,
             and PR expression)

          -  Radiologic/objective evidence of recurrence or disease progression after one line of
             chemotherapy for metastatic breast cancer MBC

          -  Availability of a representative tumor specimen that is suitable for determination of
             PD-L1 and/or additional biomarker status via central testing

          -  Eligible for capecitabine monotherapy

          -  Adequate hematologic and end-organ function, laboratory test results, obtained within
             14 days prior to initiation of study treatment.

          -  Negative HIV test at screening

          -  Negative hepatitis B surface antigen .

          -  Negative hepatitis C virus (HCV) antibody test at screening or positive HCV antibody
             test followed by a negative HCV RNA test at screening

        Inclusion Criteria for Stage 1 and Stage 2

          -  Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1
             (RECIST v1.1)

          -  Tumor accessible for biopsy

          -  For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
             during the 14 days prior to initiation of study treatment

          -  For women of childbearing potential: agreement to remain abstinent (refrain from
             heterosexual intercourse) or use contraceptive measures as outlined for each specific
             treatment arm

          -  For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
             contraceptive measures, and agreement to refrain from donating sperm, as outlined for
             each specific treatment arm

        Inclusion criteria stage 2

          -  ECOG Performance Status of 0, 1, or 2

          -  Patients randomly allocated to the control arm during Stage 1: ability to initiate
             Stage 2 treatment within 3 months after experiencing unacceptable toxicity, provided
             that Medical Monitor approval for entry into Stage 2 is obtained, or disease
             progression per RECIST v1.1 while receiving control treatment

          -  Patients randomly allocated to an experimental arm during Stage 1: ability to initiate
             Stage 2 treatment within 3 months after experiencing unacceptable toxicity not related
             to atezolizumab, disease progression per RECIST v1.1, or loss of clinical benefit as
             determined by the investigator (see Section 3.1.1.1 for details) while receiving Stage
             1 treatment

          -  Availability of a tumor specimen from a biopsy performed upon discontinuation of Stage
             1 (if deemed clinically feasible by the investigator)

        Exclusion Criteria for Stage 1

          -  Prior treatment with any of the protocol-specified study treatments

          -  Treatment with investigational therapy within 28 days prior to initiation of study
             treatment

          -  Inability to swallow medication or malabsorption condition that would alter the
             absorption of orally administered medications

          -  Treatment with sorivudine or its chemically related analogues, such as brivudine

          -  History of severe and unexpected reactions to fluoropyrimidine therapy

        Exclusion Criteria for Stage 1 and Stage 2

          -  Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
             drainage procedures (once monthly or more frequently)

          -  Uncontrolled tumor-related pain

          -  Symptomatic, untreated, or actively progressing CNS metastases

          -  History of leptomeningeal disease

          -  Active or history of autoimmune disease or immune deficiency

          -  History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
             obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of
             active pneumonitis on screening chest computed tomography (CT) scan History of
             radiation pneumonitis in the radiation field (fibrosis) is permitted.

          -  Active tuberculosis

          -  Severe infection within 4 weeks prior to initiation of study treatment

          -  Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation
             of study treatment

          -  Significant cardiovascular disease

          -  Prior allogeneic stem cell or solid organ transplantation

          -  History of malignancy other than breast cancer within 2 years prior to screening, with
             the exception of those with a negligible risk of metastasis or death

          -  Treatment with systemic immunosuppressive medication (including, but not limited to,
             corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and
             anti-tumor necrosis factor alpha agents) within 2 weeks prior to initiation of study
             treatment, or anticipation of need for systemic immunosuppressive medication during
             the course of the study

          -  Pregnancy or breastfeeding, or intention of becoming pregnant during the study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Baseline until disease progression or loss of clinical benefit ( approximately 4 years)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the end of study (approximately 4 years) as determined by the investigator according to RECIST v1.1
Safety Issue:
Description:
Measure:Disease Control Rate (DCR)
Time Frame:Baseline through end of study (approximately 4 years)
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:Randomization to death from any cause, through the end of study (approximately 4 years)
Safety Issue:
Description:
Measure:Overall Survival (at specific time-points)
Time Frame:12 and 18 months
Safety Issue:
Description:
Measure:Duration of Response (DOR)
Time Frame:Randomization until first occurrence of a documented objective response to the first recorded occurrence of disease progression or death from any cause (whichever occurs first), through end of study (approximately 4 years)
Safety Issue:
Description:
Measure:Percentage of Participants with Adverse Events
Time Frame:Baseline to end of study (approximately 4 years)
Safety Issue:
Description:
Measure:Serum Concentration of Atezolizumab
Time Frame:Day 1, Cycle 1 pre-treatment and 30 mins post-infusion; Day 1 of Cycles 2,3,4,8,12, and 16 pre-treatment; through end of study (~ 4 years); 120 days after last dose
Safety Issue:
Description:
Measure:Plasma Concentration of Ipatasertib
Time Frame:Day 15, Cycle 1 pre treatment and 1-3 hours after Ipatasertib dose;
Safety Issue:
Description:
Measure:Plasma or Serum Concentration of SNG-LIV1A
Time Frame:Day 1 Cycle, 1 pre-treatment and 30 minutes after SGN-LIV1A infusion
Safety Issue:
Description:
Measure:Plasma Concentration of Cobimetinib
Time Frame:Day 15, Cycle 1 Pre- Cobimetinib dose and 2-4 hours after Cobimetinib dose
Safety Issue:
Description:
Measure:Plasma Concentration of Capecitabine
Time Frame:Day 1, Cycle 1, 2 hours after capecitabine dose
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

March 1, 2018