Clinical Trials /

A Study to Evaluate Immunotherapy Combinations in Participants With Lung Cancer

NCT03846310

Description:

This is a Phase 1/1b, multicenter, open-label, dose-escalation and dose-expansion study to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic, and clinical activity of AB928 in combination with carboplatin and pemetrexed, with or without an anti-PD-1 antibody (pembrolizumab or AB122), in participants with non-squamous Non-Small Cell Lung Cancer (NSCLC).

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study to Evaluate Immunotherapy Combinations in Participants With Lung Cancer
  • Official Title: A Phase 1/1b Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: AB928CSP0004
  • NCT ID: NCT03846310

Conditions

  • Non Small Cell Lung Cancer Metastatic
  • Non Small Cell Lung Cancer
  • Nonsquamous Nonsmall Cell Neoplasm of Lung
  • Sensitizing EGFR Gene Mutation

Interventions

DrugSynonymsArms
AB928Dose Escalation Arm A
AB122Dose Expansion Arm 2
CarboplatinDose Escalation Arm A
PemetrexedDose Escalation Arm A
PembrolizumabDose Escalation Arm B

Purpose

This is a Phase 1/1b, multicenter, open-label, dose-escalation and dose-expansion study to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic, and clinical activity of AB928 in combination with carboplatin and pemetrexed, with or without an anti-PD-1 antibody (pembrolizumab or AB122), in participants with non-squamous Non-Small Cell Lung Cancer (NSCLC).

Detailed Description

      In the dose-escalation phase, escalating doses of AB928 in combination with carboplatin and
      pemetrexed at standard doses (Arm A), and AB928 in combination with carboplatin, pemetrexed
      and pembrolizumab (Arm B), may be assessed in participants with advanced NSCLC. Eligible
      participants will receive oral administration of AB928 as well as IV infused carboplatin,
      pemetrexed, with or without pembrolizumab in this phase. The recommended dose for expansion
      (RDE) of AB928 will be determined upon completion of the dose-escalation phase.

      In the dose-expansion phase, AB928 at RDE in combination with carboplatin and pemetrexed (Arm
      1), and AB928 at RDE in combination with carboplatin, pemetrexed, and AB122 (Arm 2) may be
      assessed in eligible NSCLC participants who harbor an EGFR mutation and have progressed on
      EGFR Tyrosine Kinase Inhibitor (TKI) treatment(s).

      Overall duration of treatment will depend on how well the treatment is tolerated.

      Treatment may continue until unacceptable toxicity or progressive disease or other reasons
      specified in the protocol.
    

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation Arm AExperimentalDose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period. The RDE of AB928 will be determined in this part with escalating doses of AB928 in combination with standard doses of carboplatin/pemetrexed chemotherapy regimen in participants with Non-Small Cell Lung Cancer.
  • AB928
  • Carboplatin
  • Pemetrexed
Dose Escalation Arm BExperimentalDose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period. The RDE of AB928 will be determined in this part with escalating doses of AB928 in combination with standard doses of carboplatin/pemetrexed chemotherapy regimen and pembrolizumab in participants with Non-Small Cell Lung Cancer.
  • AB928
  • Carboplatin
  • Pemetrexed
  • Pembrolizumab
Dose Expansion Arm 1ExperimentalThe AB928 at RDE determined from the dose escalation phase may be administered in combination with standard carboplatin and pemetrexed chemotherapy regimen in participants with Non-Small Cell Lung Cancer harboring a sensitizing EGFR mutation.
  • AB928
  • Carboplatin
  • Pemetrexed
Dose Expansion Arm 2ExperimentalThe AB928 at RDE determined from the dose escalation phase will be administered in combination with standard carboplatin and pemetrexed chemotherapy regimen and AB122 in participants with Non-Small Cell Lung Cancer harboring a sensitizing EGFR mutation.
  • AB928
  • AB122
  • Carboplatin
  • Pemetrexed

Eligibility Criteria

        Inclusion Criteria:

          -  Male or female participants; age ≥ 18 years

          -  Pathologically confirmed nonsquamous NSCLC that is metastatic, locally advanced, or
             recurrent with progression

          -  Arm A participants must fulfill one of the following:

               -  Participant has a genetic alteration (mutation or rearrangement) and has received
                  all available targeted therapy. Previous treatment with chemotherapy or PD-1/-L1
                  therapy is not allowed.

               -  Participant has not received any therapy for the disease under study and standard
                  therapy is refused.

               -  Participant has progressed on PD-1/-L1 therapy (monotherapy or combination
                  regimen). Previous treatment with chemotherapy is not allowed.

               -  Participant has progressed on PD-1/-L1 therapy (monotherapy or combination
                  regimen) and has received less than 4 cycles of carboplatin/pemetrexed and
                  further chemotherapy is appropriate.

               -  Participant has received any number of prior treatments and is without
                  alternative or curative therapy.

          -  Arm B participants must fulfill one of the following:

               -  Participant has a genetic alteration (mutation or rearrangement) and has received
                  all available targeted therapy. Previous treatment with chemotherapy or PD-1/-L1
                  therapy is not allowed.

               -  Participant has not received any therapy for the disease under study and standard
                  therapy is refused.

               -  Participant has received any number of prior treatments and is without
                  alternative or curative therapy.

          -  Arm 1 and Arm 2 participants must have a sensitizing epidermal growth factor receptor
             (EGFR) mutation and failed treatment with 1 TKI (or 1-2 TKIs for tumors with T790M
             mutation). Previous treatment with chemotherapy or PD-1/-L1 therapy is not allowed.

          -  No TKI therapy within 5 days of Cycle 1 Day 1

          -  Must have at least 1 measurable lesion per Response Evaluation Criteria in Solid
             Tumors (RECIST v1.1)

          -  Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.

          -  Confirm that an archival tissue sample is available and ≤ 24 months old; if not, a new
             biopsy of a tumor lesion must be obtained at screening

          -  Adequate organ and marrow function

        Exclusion Criteria:

          -  Use of any live vaccines against infectious diseases within 4 weeks (28 days) of
             initiation of investigational product

          -  Is pregnant or breastfeeding or expecting to conceive or father children within the
             projected duration of the study, starting with the pre-screening or screening visit
             through 30 days after the last dose of investigational product for non-PD-1-containing
             regimens and through 90 days after the last dose of investigational products for
             PD-1-containing regimens

          -  Any active autoimmune disease or a documented history of autoimmune disease or
             syndrome that required systemic treatment in the past 2 years (ie, with use of
             disease-modifying agents, corticosteroids, or immunosuppressive drugs), except for
             vitiligo or resolved childhood asthma/atopy

          -  Prior malignancy active within the previous 2 years except for locally curable cancers
             that have been apparently cured, such as basal or squamous cell skin cancer,
             superficial bladder cancer, or carcinoma in situ of the cervix, breast, or prostate
             cancer

          -  Prior use of an adenosine pathway targeting agent

          -  Use of other investigational drugs (drugs not marketed for any indication) within 28
             days or at least 5 half-lives (whichever is longer) before investigational product
             administration
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of participants with Adverse Events
Time Frame:From first study treatment administration until up to 90 days after the last dose (Approximately 1 year)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Percentage of participants with anti-drug antibodies to AB122
Time Frame:Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 days post last dose (i.e. in total approximately 5 months).
Safety Issue:
Description:
Measure:Plasma concentration of AB928
Time Frame:Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 days post last dose (i.e. in total approximately 5 months).
Safety Issue:
Description:
Measure:Serum concentration of AB122
Time Frame:Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 days post last dose (i.e. in total approximately 5 months).
Safety Issue:
Description:
Measure:Progression Free Survival (PFS) as determined by Investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time Frame:From start of treatment up to the first occurrence of progressive disease or death from any cause, whichever occurs first (up to approximately 3-5 years)
Safety Issue:
Description:
Measure:Overall Survival (OS) as determined by the Investigator according to RECIST v1.1
Time Frame:From study start of treatment up to death from any cause (up to approximately 3-5 years)
Safety Issue:
Description:
Measure:Duration of Response as determined by the Investigator according to RECIST v1.1
Time Frame:From the date of first occurrence of a documented objective response to first documentation of disease progression or death from any cause, whichever occurs first (up to approximately 3-5 years)
Safety Issue:
Description:
Measure:Percentage of Participants with Disease Control (complete response, partial response, or stable disease) for >6 months as determined by the Investigator per RECIST v1.1
Time Frame:From study enrollment until disease progression or loss of clinical benefit (up to approximately 3-5 years)
Safety Issue:
Description:
Measure:Percentage of participants with Objective Response as determined by Investigator according to RECIST v1.1
Time Frame:From study enrollment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 3-5 years)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Arcus Biosciences, Inc.

Last Updated

January 16, 2020