Clinical Trials /

A Phase 1 Study With ABBV-CLS-484 in Subjects With Locally Advanced or Metastatic Tumors

NCT04777994

Description:

The study will assess the safety, PK, PD, and preliminary efficacy of ABBV-CLS-484 as monotherapy and in combination with a PD-1 targeting agent. The trial aims to establish a safe, tolerable, and efficacious dose of ABBV-CLS-484 as monotherapy and in combination. The study will be conducted in three parts. Part 1 Monotherapy Dose Escalation, Part 2 Combination Dose Escalation and Part 3 Dose Expansion (Monotherapy and Combination therapy). Part 1, ABBV-CLS-484 will be administered alone in escalating dose levels to eligible subjects who have advanced solid tumors. Part 2, ABBV-CLS-484 will be administered at escalating dose levels in combination with a PD-1 targeting agent to eligible subjects who have advanced solid tumors. Part 3, ABBV-CLS-484 will be administered alone as a monotherapy at the determined recommended dose in subjects with locally advanced or metastatic, relapsed or refractory head and neck squamous cell carcinoma (HNSCC), relapsed or refractory non-small cell lung cancer (NSCLC), and advanced clear cell renal cell carcinoma (ccRCC). ABBV-CLS-484 will also be administered at the determined recommended dose in combination with a PD-1 targeting agent in subjects with locally advanced or metastatic, relapsed or refractory gastric or GEJ adenocarcinoma.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Adenocarcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase 1 Study With ABBV-CLS-484 in Subjects With Locally Advanced or Metastatic Tumors
  • Official Title: A Phase 1, Multi-center, Open Label First-in-Human Study With ABBV-CLS-484 Alone and in Combination in Subjects With Locally Advanced or Metastatic Tumors

Clinical Trial IDs

  • ORG STUDY ID: M20-431
  • NCT ID: NCT04777994

Conditions

  • Advanced Solid Tumor Cancer

Interventions

DrugSynonymsArms
ABBV-CLS-484Combination Dose Escalation
Programmed Cell Death-1 (PD-1) InhibitorCombination Dose Escalation

Purpose

The study will assess the safety, PK, PD, and preliminary efficacy of ABBV-CLS-484 as monotherapy and in combination with a PD-1 targeting agent. The trial aims to establish a safe, tolerable, and efficacious dose of ABBV-CLS-484 as monotherapy and in combination. The study will be conducted in three parts. Part 1 Monotherapy Dose Escalation, Part 2 Combination Dose Escalation and Part 3 Dose Expansion (Monotherapy and Combination therapy). Part 1, ABBV-CLS-484 will be administered alone in escalating dose levels to eligible subjects who have advanced solid tumors. Part 2, ABBV-CLS-484 will be administered at escalating dose levels in combination with a PD-1 targeting agent to eligible subjects who have advanced solid tumors. Part 3, ABBV-CLS-484 will be administered alone as a monotherapy at the determined recommended dose in subjects with locally advanced or metastatic, relapsed or refractory head and neck squamous cell carcinoma (HNSCC), relapsed or refractory non-small cell lung cancer (NSCLC), and advanced clear cell renal cell carcinoma (ccRCC). ABBV-CLS-484 will also be administered at the determined recommended dose in combination with a PD-1 targeting agent in subjects with locally advanced or metastatic, relapsed or refractory gastric or GEJ adenocarcinoma.

Trial Arms

NameTypeDescriptionInterventions
Monotherapy Dose EscalationExperimentalABBV-CLS-484 will be administered as a monotherapy in subjects with solid tumors
  • ABBV-CLS-484
Combination Dose EscalationExperimentalABBV-CLS-484 will be administered in combination with Programmed Cell Death-1 Inhibitor in subjects with solid tumors
  • ABBV-CLS-484
  • Programmed Cell Death-1 (PD-1) Inhibitor
Monotherapy ExpansionExperimentalABBV-CLS-484 will be administered at the determined recommended dose in subjects with locally advanced or metastatic, relapsed or refractory head and neck squamous cell carcinoma (HNSCC), relapsed or refractory non-small cell lung cancer (NSCLC), and advanced clear cell renal cell carcinoma (ccRCC)
  • ABBV-CLS-484
Combination ExpansionExperimentalABBV-CLS-484 will be administered at the determined recommended dose in combination with Programmed Cell Death-1 Inhibitor in subjects with locally advanced or metastatic, relapsed or refractory gastric or GEJ adenocarcinoma
  • ABBV-CLS-484
  • Programmed Cell Death-1 (PD-1) Inhibitor

Eligibility Criteria

        Inclusion Criteria:

          -  Must weigh at least 35 kilograms (kg).

          -  An Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

          -  Life expectancy of ≥ 12 weeks.

          -  Laboratory values meeting protocol criteria.

          -  QT interval corrected for heart rate < 470 msec (using Fridericia's correction), and
             no clinically significant electrocardiographic findings.

          -  Measurable disease defined by RECIST 1.1 criteria.

        For Monotherapy and Combination Dose Escalation:

        • Subjects with histologically or cytologically proven metastatic or locally advanced
        tumors, for which no effective standard therapy exists, or where standard therapy has
        failed. Subjects must have received at least 1 prior systemic anticancer therapy for the
        indication being considered.

        For Monotherapy Dose Expansion only:

          -  Subjects must have received 1 prior line containing PD-1/PD-L1 targeted therapy with a
             best response of CR/PR/stable disease by RECIST v1.1 for greater than 6 months; AND

          -  Must have been previously treated with 1 or more prior lines of therapy in the locally
             advanced or metastatic setting with the following tumor types:

               -  Relapsed/refractory HNSCC

               -  Relapsed/refractory NSCLC

               -  Advanced ccRCC

        For Combination Dose Expansion only:

          -  Subjects with gastric or GEJ adenocarcinoma whose tumors express PD-L1 (CPS ≥1)

          -  Must not have received a PD-1/PD-L1 targeting agent, or other immune-oncology agents
             as part of a prior line of therapy;

          -  Must have received, and progressed on, at least 2 prior lines of chemotherapy in the
             locally advanced or metastatic setting; •. If tumor is HER2/neu positive, subject must
             have received prior treatment with an approved HER2 targeting therapy.

        Exclusion Criteria:

          -  Untreated brain or meningeal metastases (i.e., subjects with history of metastases are
             eligible provided they do not require ongoing steroid treatment and have shown
             clinical and radiographic stability for at least 28 days after definitive therapy)

          -  Unresolved Grade 2 or higher toxicities related to previous anticancer therapy except
             alopecia.

          -  Unresolved Grade 2 or higher peripheral neuropathy.

          -  History of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.

          -  Recent history (within 6 months) of congestive heart failure (defined as New York
             Heart Association, Class 2 or higher), ischemic cardiovascular event, pericarditis, or
             clinically significant pericardial effusion or arrythmia.

          -  Recent history (within 6 months) of Childs-Pugh B or C classification of liver
             disease.

          -  History of clinically significant medical and/or psychiatric conditions or any other
             reason that, in the opinion of the investigator, would interfere with the subject's
             participation in this study or would make the subject an unsuitable candidate to
             receive study drug.

          -  History of uncontrolled, clinically significant endocrinopathy.

          -  Known gastrointestinal disorders making absorption of oral medications problematic;
             subject must be able to swallow capsules.

          -  If treated with a PD-1/aPD-L1 targeting or other immune-oncology agents in the past,
             excluded if had prior pneumonitis, prior Grade 3 or higher immune mediated toxicity,
             hypersensitivity to administered drug or drug related toxicity requiring
             discontinuation.

          -  Active autoimmune disease requiring systemic treatment in past 2-years (exceptions for
             endocrinopathies, vitiligo or atopic conditions).

          -  History of solid organ transplant or allogeneic stem cell transplant.

          -  History of other malignancy, with the following exceptions:

               -  No known active disease present for ≥ 3 years before first dose of study
                  treatment and felt to be at low recurrence by investigator.

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

               -  Adequately treated carcinoma in situ without evidence of disease.

          -  History of interstitial lung disease or pneumonitis.

          -  Major surgery ≤ 28 days prior to first dose of study drug

          -  Known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection
             per local testing practices.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Escalation: Maximum Observed Plasma/Serum Concentration (Cmax) Of ABBV-CLS-484 (Monotherapy)
Time Frame:Baseline Up to Approximately Day 42
Safety Issue:
Description:Maximum plasma/serum concentration of ABBV-CLS-484

Secondary Outcome Measures

Measure:Dose Escalation: Objective Response Rate (ORR) Of ABBV-CLS-484 Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Monotherapy)
Time Frame:Baseline through Study Completion (approximately 3 years)
Safety Issue:
Description:ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment
Measure:Dose Escalation: Objective Response Rate (ORR) Of ABBV-CLS-484 And PD-1 Targeting Agent Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Combination therapy)
Time Frame:Baseline through Study Completion (approximately 3 years)
Safety Issue:
Description:ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Calico Life Sciences LLC

Trial Keywords

  • Cancer
  • Tumor
  • anti-PD-1
  • ABBV-CLS-484
  • clear cell renal cell carcinoma (ccRCC)
  • gastroesophageal junction (GEJ)
  • head and neck squamous cell carcinoma (HNSCC)
  • non-small cell lung cancer (NSCLC)
  • relapsed or refractory (R/R)
  • gastric
  • GEJ adenocarcinoma

Last Updated

April 6, 2021