Clinical Trials /

QUILT-3.055: A Study of ALT-803 in Combination With PD-1/PD-L1 Checkpoint Inhibitor in Patients With Advanced Cancer

NCT03228667

Description:

This is a Phase IIb, single-arm, multicohort, open-label multicenter study of ALT-803 in combination with an FDA-approved PD-1/PD-L1 checkpoint inhibitor in patients with advanced cancers who have progressed following an initial response to treatment with PD-1/PD-L1 checkpoint inhibitor therapy. All patients will receive the combination treatment of PD-1/PD-L1 checkpoint inhibitor plus ALT-803 for up to 16 cycles. Each cycle is six weeks in duration. All patients will receive ALT-803 once every 3 weeks. Patients will also receive the same checkpoint inhibitor that they received during their previous therapy. Radiologic evaluation will occur at the end of each treatment cycle. Treatment will continue for up to 2 years, or until the patient experiences confirmed progressive disease or unacceptable toxicity, withdraws consent, or if the Investigator feels it is no longer in the patient's best interest to continue treatment. Patients will be followed for disease progression, post-therapies, and survival through 24 months past administration of the first dose of study drug.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Cervical Carcinoma
  • Gastric Adenocarcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Hepatocellular Carcinoma
  • Malignant Solid Tumor
  • Melanoma
  • Merkel Cell Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Renal Cell Carcinoma
  • Small Cell Lung Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: QUILT-3.055: A Study of ALT-803 in Combination With PD-1/PD-L1 Checkpoint Inhibitor in Patients With Advanced Cancer
  • Official Title: QUILT-3.055: A Phase IIb, Single-Arm, Multicohort, Open-Label Study of ALT-803 in Combination With PD-1/PD-L1 Checkpoint Inhibitor in Patients Who Have Disease Progression Following an Initial Response to Treatment With PD-1/PD-L1 Checkpoint Inhibitor Therapy

Clinical Trial IDs

  • ORG STUDY ID: CA-ALT-803-02-17
  • NCT ID: NCT03228667

Conditions

  • Non-Small Cell Lung Cancer
  • Small Cell Lung Cancer
  • Urothelial Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Merkel Cell Carcinoma
  • Melanoma
  • Renal Cell Carcinoma
  • Gastric Cancer
  • Cervical Cancer
  • Hepatocellular Carcinoma
  • Microsatellite Instability
  • Mismatch Repair Deficiency
  • Colorectal Cancer

Interventions

DrugSynonymsArms
ALT-803 + PembrolizumabCohort 1
ALT-803 + NivolumabCohort 1
ALT-803 + AtezolizumabCohort 1
ALT-803 + AvelumabCohort 1

Purpose

This is a Phase IIb, single-arm, multicohort, open-label multicenter study of ALT-803 in combination with an FDA-approved PD-1/PD-L1 checkpoint inhibitor in patients with advanced cancers who have progressed following an initial response to treatment with PD-1/PD-L1 checkpoint inhibitor therapy. All patients will receive the combination treatment of PD-1/PD-L1 checkpoint inhibitor plus ALT-803 for up to 16 cycles. Each cycle is six weeks in duration. All patients will receive ALT-803 once every 3 weeks. Patients will also receive the same checkpoint inhibitor that they received during their previous therapy. Radiologic evaluation will occur at the end of each treatment cycle. Treatment will continue for up to 2 years, or until the patient experiences confirmed progressive disease or unacceptable toxicity, withdraws consent, or if the Investigator feels it is no longer in the patient's best interest to continue treatment. Patients will be followed for disease progression, post-therapies, and survival through 24 months past administration of the first dose of study drug.

Trial Arms

NameTypeDescriptionInterventions
Cohort 1OtherPatients with any of the cancers listed below who have progressed on or after single-agent checkpoint inhibitor therapy after experiencing an initial complete response (CR) or partial response (PR) while taking a checkpoint inhibitor. 1a - Non-small cell lung cancer 1b - Small cell lung cancer 1c - Urothelial carcinoma 1d - Head and neck squamous cell carcinoma 1e - Merkel cell carcinoma 1f - Melanoma 1g - Renal cell carcinoma 1h - Gastric cancer 1i - Cervical cancer 1j - Hepatocellular carcinoma 1k - Microsatellite instability-high or mismatch repair deficient solid tumor cancer or colorectal cancer
  • ALT-803 + Pembrolizumab
  • ALT-803 + Nivolumab
  • ALT-803 + Atezolizumab
  • ALT-803 + Avelumab
Cohort 2OtherPatients with NSCLC whose tumors have high PD-L1 expression (TPS ≥ 50%) and who relapsed on a PD-1 checkpoint inhibitor after experiencing an initial CR or PR when they received checkpoint inhibitor as a single-agent for first-line treatment.
  • ALT-803 + Pembrolizumab
Cohort 3OtherPatients with NSCLC who had an initial CR or PR but subsequently relapsed on maintenance PD-1 checkpoint inhibitor therapy when they initially received checkpoint inhibitor therapy in combination with chemotherapy as first-line treatment.
  • ALT-803 + Pembrolizumab
Cohort 4ExperimentalPatients who are currently receiving PD-1/PD-L1 checkpoint inhibitor therapy and have disease progression after experiencing stable disease (SD) for at least 6 months during their previous treatment with PD-1/PD-L1 checkpoint inhibitor therapy.
  • ALT-803 + Pembrolizumab
  • ALT-803 + Nivolumab
  • ALT-803 + Atezolizumab
  • ALT-803 + Avelumab

Eligibility Criteria

        Inclusion Criteria:

        • Voluntary written informed consent and HIPAA authorization and agree to comply with all
        protocol-specified procedures and follow-up evaluations

          1. Cohort 1 will enroll patients who have disease progression per RECIST v1.1 on or after
             single-agent checkpoint inhibitor therapy after experiencing an initial response (ie,
             confirmed CR or PR by RECIST V1.1) while taking checkpoint inhibitor therapy. Patients
             will be enrolled into distinct cohorts (1a-1k) based on cancer type.

             Patients must have been treated with checkpoint inhibitor therapy after progressing on
             SoC therapy for their disease, as per FDA indication detailed below:

               -  1a - For metastatic squamous or nonsquamous NSCLC with progression on or after
                  nivolumab, pembrolizumab, or atezolizumab, initial SoC therapy must have been for
                  disease with progression on or after one prior platinum doublet-based
                  chemotherapy regimen. Patients with EGFR or ALK genomic tumor aberrations should
                  have had disease progression on FDA-approved targeted therapy for these
                  aberrations prior to receiving checkpoint inhibitor.

               -  1b - For metastatic SCLC with disease progression on or after nivolumab
                  monotherapy, initial SoC treatment must have been for disease with progression
                  after platinum-based chemotherapy and at least one other line of therapy prior to
                  receiving checkpoint.

               -  1c - Locally advanced or metastatic urothelial carcinoma as follows:

               -  For patients with progression on or after nivolumab monotherapy, initial SoC must
                  have been for disease with progression on or after platinum-based chemotherapy or
                  within 12 months of neoadjuvant or adjuvant treatment with platinum-based
                  chemotherapy.

               -  For patients with disease progression on or after pembrolizumab, initial SoC
                  therapy may have been for locally advanced or metastatic urothelial carcinoma
                  ineligible for cisplatin-containing chemotherapy with PD-L1 tumor expression of
                  CPS ≥ 10 (as determined by FDA-approved test), OR metastatic urothelial carcinoma
                  not eligible for any platinum-containing chemotherapy regardless of PD-L1 status,
                  OR locally advanced or metastatic urothelial carcinoma with progression on or
                  after platinum-based chemotherapy or within 12 months of neoadjuvant or adjuvant
                  treatment with platinum-based chemotherapy.

               -  For patients with disease progression on or after atezolizumab, initial SoC
                  therapy may have been for locally advanced or metastatic urothelial carcinoma not
                  eligible for cisplatin-based chemotherapy that expresses PD-L1 (PD-L1 stained
                  tumor-infiltrating immune cells [IC] covering ≥ 5% of the tumor area, as
                  determined by an FDA-approved test), OR not eligible for cisplatin-based
                  chemotherapy regardless of PD-L1 status, OR with progression on or after
                  platinum-based chemotherapy or within 12 months of neoadjuvant or adjuvant
                  treatment with platinum-based chemotherapy.

               -  For patients with disease progression on or after avelumab, initial SoC therapy
                  may have been for locally advanced or metastatic urothelial carcinoma with
                  progression on or after platinum-based chemotherapy or within 12 months of
                  neoadjuvant or adjuvant treatment with platinum-based chemotherapy.

               -  1d - Recurrent or metastatic HNSCC as follows:

               -  For patients with disease progression on or after nivolumab monotherapy, initial
                  SoC treatment must have been for disease with progression on or within 6 months
                  of a platinum-based therapy administered in the adjuvant, neoadjuvant, primary
                  (unresectable locally advanced), or metastatic setting.

               -  For patients with disease progression on or after pembrolizumab monotherapy,
                  initial SoC treatment must have been for disease with progression on or after
                  platinum-based chemotherapy, or after platinum-based chemotherapy administered as
                  part of induction, concurrent, or adjuvant therapy.

               -  1e - For histologically confirmed metastatic MCC with progression on or after
                  avelumab or pembrolizumab, initial SoC therapy must have been for disease with
                  progression on or after chemotherapy administered for distant metastatic disease;
                  OR recurrent locally advanced or metastatic MCC not treated with prior systemic
                  therapy for advanced disease.

               -  1f - Metastatic melanoma as follows:

               -  For patients with disease progression on or after nivolumab administered as a
                  single agent, in combination with ipilimumab, or in the adjuvant setting, initial
                  SoC treatment must have been for unresectable or metastatic melanoma with
                  progression on or after ipilimumab treatment, and if BRAF V600 mutation positive,
                  a BRAF inhibitor; OR BRAF V600 wild-type unresectable or metastatic melanoma
                  previously untreated in the metastatic setting; OR previously untreated,
                  unresectable, or metastatic melanoma not previously treated with anti-CTLA4
                  antibody; OR completely resected melanoma with lymph node involvement, or stage
                  IIIB/C or stage IV metastatic disease.

               -  For patients with disease progression on or after pembrolizumab therapy, initial
                  SoC treatment must have been for unresectable or metastatic melanoma with no
                  prior ipilimumab, and no more than 1 prior systemic treatment for metastatic
                  disease. Patients with BRAF V600E mutation-positive melanoma were not required to
                  have received prior BRAF inhibitor therapy; OR unresectable or metastatic
                  melanoma with progression, refractory to ≥ 2 doses of ipilimumab (3 mg/kg or
                  higher) and, if BRAF V600 mutation-positive, a BRAF or MEK inhibitor, and disease
                  progression within 24 weeks following the last dose of ipilimumab.

               -  1g - For advanced RCC with progression on or after nivolumab monotherapy, initial
                  SoC therapy must have been for disease that progressed after 1 or 2 prior
                  anti-angiogenic therapy regimens. For intermediate or poor risk previously
                  untreated advanced RCC, patients must have progressed on or after nivolumab +
                  ipilimumab.

               -  1h - For recurrent locally advanced or metastatic gastric or gastroesophageal
                  junction adenocarcinoma with progression on or after pembrolizumab, initial SoC
                  therapy must have been for disease that progressed on or after ≥ 2 prior lines of
                  therapy including fluoropyrimidine- and platinum-containing chemotherapy and, if
                  appropriate, HER2/neu-targeted therapy. Tumors must express PD-L1 (combined
                  positive score [CPS] ≥ 1), as determined by an FDA-approved test.

               -  1i - For recurrent or metastatic cervical cancer with progression on or after
                  pembrolizumab, initial SoC therapy must have been for disease that progressed on
                  or after chemotherapy. Tumors must express PD-L1 (CPS ≥ 1), as determined by an
                  FDA-approved test.

               -  1j - For HCC with progression on or after pembrolizumab, initial SoC treatment
                  must have been for disease that progressed on or after sorafenib or intolerant to
                  sorafenib. Patients must have had measureable disease and Child-Pugh class A
                  liver impairment. For HCC with progression on or after nivolumab, initial SoC
                  treatment must have been for histologically confirmed HCC with progression on
                  sorafenib or intolerant to sorafenib, and Child-Pugh class A.

               -  1k -Unresectable or metastatic MSI-H or dMMR solid tumors as follows:

               -  For patients with progression on or after nivolumab administered as a single
                  agent or in combination with ipilimumab, initial SoC therapy must have been for
                  MSI-H or dMMR metastatic CRC with progression on or after treatment with a
                  fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

               -  For patients with progression on or after pembrolizumab, initial SoC therapy must
                  have been for unresectable or metastatic MSI-H or dMMR solid tumors with
                  progression after prior treatment and no satisfactory alternative treatment
                  options; OR unresectable or metastatic MSI-H or dMMR CRC with progression after
                  treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.

          2. For cohort 2, patients with NSCLC whose tumors have high PD-L1 expression (TPS ≥ 50%)
             and who have disease progression by RECIST v1.1 on a PD-1 checkpoint inhibitor after
             experiencing an initial confirmed CR or PR by RECIST v1.1 when they received
             checkpoint inhibitor as a single-agent for first-line treatment.

          3. For cohort 3, patients with NSCLC who had an initial confirmed CR or PR by RECIST v1.1
             but subsequently relapsed (ie, disease progression by RECIST v1.1) on maintenance PD-1
             checkpoint inhibitor therapy when they initially received checkpoint inhibitor therapy
             in combination with chemotherapy as first-line treatment.

          4. For cohort 4, patients with NSCLC, HNSCC, RCC, or urothelial carcinoma who are
             currently receiving PD-1/PD-L1 checkpoint inhibitor therapy and have disease
             progression after experiencing SD by RECIST v1.1 for at least 6 months during their
             previous treatment with PD-1/PD-L1 checkpoint inhibitor therapy.

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

               -  Measurable disease by CT or MRI, as defined by RECIST v1.1

               -  Treatment of at least 3 months and 1 imaging assessment indicative of a confirmed
                  CR or PR (in accordance with RECIST V1.1) with checkpoint inhibitor (no more than
                  6 weeks of treatment interruption immediately prior to study enrollment).

               -  Patients with genomic tumor aberrations should have received prior treatment with
                  an FDA-approved targeted therapy (if available)

               -  Current progressive disease, as defined by RECIST v1.1

               -  Adequate organ system function within 14 days of baseline:

               -  ANC ≥ 750/µL (≥0.75 x 10^9/L)

               -  Platelets ≥ 100,000/µL (≥100 x 10^9/L)

               -  Hemoglobin > 8 g/dL

               -  Total bilirubin < 2.0 x ULN

               -  AST < 3.0 x ULN

               -  ALT < 3.0 x ULN

               -  eGFR > 45 mL/min

               -  Men and women, ≥ 18 years of age

               -  Female participants / women of childbearing potential (WOCBP) must adhere to
                  using a medically accepted method of birth control up to 28 days prior to
                  screening and agree to continue its use during the study or be surgically
                  sterilized (e.g., hysterectomy or tubal ligation) and males must agree to use
                  barrier methods of birth control while on study. WOCBP must agree to use
                  effective contraception during treatment and for at least 5 months following the
                  last dose of study treatment.

               -  Women of child-bearing potential must have a negative serum pregnancy test during
                  Screening and a negative urine pregnancy test within 24 hours prior to first dose
                  of study treatment. Non-childbearing is defined as greater than one year
                  postmenopausal or surgically sterilized.

        Exclusion Criteria:

          -  Patients with CNS metastases with the following exceptions:

          -  Patient untreated CNS metastases with 4 or fewer sites of disease, with no single site
             larger than 20mm, are eligible if they are asymptomatic and not requiring steroids at
             any dose. Patients with asymptomatic CNS metastases may be treated with radiosurgery
             before or during therapy on trial without treatment delays.

          -  Patients with treated, symptomatic CNS metastases are eligible if they are
             neurologically returned to baseline (except for residual signs or symptoms related to
             the CNS treatment) for at least 2 weeks prior to registration AND either off
             corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or
             equivalent).

          -  New York Heart Association (NYHA) Class III or IV heart failure, uncontrollable
             supraventricular arrhythmias, any history of a ventricular arrhythmia, or other
             clinical signs of severe cardiac dysfunction

          -  Symptomatic congestive heart failure, unstable angina pectoris, or myocardial
             infarction within 6 months of enrollment

          -  Known autoimmune disease requiring active treatment.

          -  History of interstitial lung disease and/or immune mediated pneumonitis

          -  Known HIV-positive

          -  Active systemic infection requiring parenteral antibiotic therapy

          -  Positive hepatitis C serology or active hepatitis B infection

          -  Any ongoing toxicity from prior anti-cancer treatment that, in the judgement of the
             investigator, may interfere with study treatment. All toxicities attributed to prior
             anti-cancer therapy other than alopecia and fatigue must resolve to grade 1 (NCI CTCAE
             version 4) or baseline prior to enrollment. Eligible patients must not require more
             than 10 mg/day prednisone (or equivalent dose).

          -  Previous malignancies (except non-melanoma skin cancers, in situ bladder cancer, in
             situ gastric or in situ colon cancers, in situ cervical cancers/dysplasia or breast
             carcinoma in situ) unless a complete remission was achieved at least 1 year prior to
             study entry and no additional therapy is required or anticipated to be required during
             the study period

          -  No other illness that in the opinion of the investigator would exclude the subject
             from participating in the study

          -  Patients in which treatment with PD-1/PD-L1 checkpoint inhibitor is contraindicated

          -  Patients who have received another investigational agent within the previous 3 months

          -  Women who are pregnant or nursing
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate
Time Frame:24 months
Safety Issue:
Description:Assess the anti-tumor activity of ALT-803 in combination with a PD-1/PD-L1 checkpoint inhibitor in patients with advanced cancers who have progressed following an initial response to treatment with PD-1/PD-L1 checkpoint inhibitors.

Secondary Outcome Measures

Measure:Disease-specific Survival
Time Frame:24 months
Safety Issue:
Description:Assess time from first treatment to death resulting from cancer.
Measure:Overall Survival
Time Frame:24 months
Safety Issue:
Description:Assess time from first treatment to death resulting from any cause.
Measure:Time to Response
Time Frame:24 months
Safety Issue:
Description:Assess time to response
Measure:Duration of Response
Time Frame:24 months
Safety Issue:
Description:Assess duration of response
Measure:Incidence of Adverse Events
Time Frame:24 months
Safety Issue:
Description:Assess incidence of adverse events.
Measure:Quality of Life (QOL)
Time Frame:24 months
Safety Issue:
Description:Compare changes in QOL scores from baseline.
Measure:Progression-free Survival
Time Frame:24 months
Safety Issue:
Description:Assess amount of time disease does not get worse after first treatment.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Altor BioScience

Trial Keywords

  • Pembrolizumab
  • Nivolumab
  • Non-Small Cell Lung Cancer (NSCLC)
  • Immunotherapy
  • Interleukin-15
  • PD-1 Checkpoint Inhibitor
  • ALT-803
  • Atezolizumab
  • Avelumab
  • Small Cell Lung Cancer (SCLC)
  • Urothelial Carcinoma
  • Head and Neck Squamous Cell Carcinoma (HNSCC)
  • Merkel Cell Carcinoma (MCC)
  • Melanoma
  • Renal Cell Carcinoma (RCC)
  • Gastric Cancer
  • Cervical Cancer
  • Hepatocellular Carcinoma (HCC)
  • Microsatellite Instability-High (MSI-H)
  • PD-L1 Checkpoint Inhibitor
  • Mismatch Repair Deficient (dMMR) Solid Tumor Cancer
  • Colorectal Cancer (CRC)

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