First-in-Human Dose Escalation Trial of ATRC-101 in Adults With Advanced Solid Malignancies

Brief Title

A Dose Escalation Trial of ATRC-101 in Adults With Advanced Solid Malignancies

Official Title

A Phase 1b Dose Escalation Trial to Investigate the Safety, Tolerability, Pharmacokinetics, and Biological Activity of ATRC-101 as Monotherapy and in Combination With Other Anticancer Agents in Adults With Advanced Solid Malignancies

Brief Summary

      ATRC-101-A01 is a Phase 1b, open-label dose escalation trial of ATRC-101, an engineered fully
      human immunoglobulin G, subclass 1 (IgG1) antibody derived from a naturally occurring human
      antibody. The safety, tolerability, PK, and biological activity of ATRC-101 will be
      characterized when administered every two weeks (Q2W) or every 3 weeks (Q3W) as a monotherapy
      or in combination with other anticancer agents.
    

Detailed Description

      For the ATRC-101 monotherapy cohorts, enrollment is restricted to adults with breast cancer
      (BC), non-small cell lung cancer (NSCLC), colorectal cancer (CRC), ovarian cancer, and acral
      melanoma.

      For the pembrolizumab combination therapy cohort, enrollment is restricted to adults with
      NSCLC, CRC (only MSI-H or dMMR), melanoma (with the exception of uveal melanoma),
      hepatocellular carcinoma (HCC), head and neck squamous cell carcinoma (HNSCC), esophageal
      squamous cell carcinoma (ESCC), or urothelial carcinoma (UC), that have been treated with
      pembrolizumab and have progressed or have achieved stable disease and who, in the judgment of
      their treating physicians, could benefit from the addition of ATRC-101 to improve or maintain
      their response.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Incidence of DLTs, treatment emergent adverse events (TEAEs), and changes in safety parameters

Secondary Outcome

 Maximum plasma concentration (Cmax) of ATRC-101

Condition

Breast Cancer

Intervention

ATRC-101

Study Arms / Comparison Groups

 ATRC-101 Q3W
Description:  

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

160

Start Date

February 11, 2020

Completion Date

March 2025

Primary Completion Date

December 2024

Eligibility Criteria

        Inclusion Criteria:

          -  Confirmed diagnosis of:

               1. For the monotherapy cohorts: Metastatic or unresectable BC, NSCLC, CRC, ovarian
                  cancer, or acral melanoma that is refractory to standard therapy or for which no
                  standard therapy exists. Participants who are considered intolerant of or
                  ineligible for standard therapy(ies), as well as participants who have been
                  offered but refused standard therapy(ies), may also be eligible.

               2. For the pembrolizumab combination therapy cohort: Metastatic or unresectable
                  NSCLC, CRC (only MSI-H or dMMR), melanoma (with the exception of uveal melanoma),
                  HCC, HNSCC, ESCC, or UC with prior or ongoing pembrolizumab treatment and have
                  progressed or have achieved stable disease and who, in the judgment of their
                  treating physicians, could benefit from the addition of ATRC-101 to improve or
                  maintain their response.

                    1. Individuals with BRAF mutant melanoma must have received BRAF inhibitors
                       alone or in combination with a MEK inhibitor, if indicated

                    2. Individuals with NSCLC should have received platinum-based therapy unless
                       contraindicated

          -  Measurable disease based on RECIST v1.1, as assessed by the local site
             investigator/radiologist. Lesions situated in an area treated with radiation or other
             loco-regional therapy are considered measurable only if the progression has been
             demonstrated in such lesions following loco-regional therapy.

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

          -  Adequate organ and marrow function (i.e. without chronic, ongoing growth factor or
             transfusion support) at Screening as defined by the following laboratory parameters:

               -  Absolute neutrophil count (ANC) ≥ 1000/µL

               -  Absolute lymphocyte count (ALC) ≥ 500/ µL

               -  Platelet count ≥ 75,000/µL

               -  Hemoglobin ≥ 9.0 g/dL

               -  PT/INR, aPTT ≤ 1.5 x ULN unless participant is receiving a stable dose of
                  therapeutic anticoagulation

               -  Albumin ≥ 3.0 g/dL

               -  Creatinine clearance or eGFR ≥ 30 mL/min as estimated by the Cockcroft-Gault
                  equation

               -  AST/ALT ≤ 2 x ULN. If documented liver metastases, then ≤ 5X ULN

               -  Bilirubin ≤ 2 x ULN; or bilirubin ≤ 3 x ULN if due to Gilbert's or Crigler-Najjar
                  disease

          -  Available representative tumor specimens in paraffin blocks (preferred) or ≥ 20
             unstained slides, with an associated pathology report, obtained after last systemic
             anti-cancer therapy and within 60 days prior to the planned first dose of
             investigational product. If fewer than 20 unstained slides are available, a discussion
             with the Medical Monitor is required prior to enrollment. If an archived sample is not
             available, participant must have a tumor that is amenable to biopsy without
             unacceptable risk of a major procedural complication and consent to have a tumor
             biopsy. Tumor lesions used for biopsy should not be lesions used as RECIST 1.1 target
             lesions unless there are no other lesions suitable for biopsy. If a RECIST target
             lesion is used for biopsy, the lesion must be ≥ 2cm in longest diameter.

             a. For the pembrolizumab combination therapy cohort: A biopsy collected within 60 days
             of the planned first dose of investigational product while the participant is
             receiving pembrolizumab is acceptable.

          -  Women of childbearing potential (WOCBP) and fertile males with partners who are WOCBP
             must use highly effective contraception (per CTFG 2014) from first dose and through 90
             days after final dose of investigational product 8. Willing and able to provide
             written informed consent and able to comply with all trial procedures.

        Exclusion Criteria:

          -  Disease that is suitable for local therapy administered with curative intent.

          -  Malignant disease other than the malignancy to be investigated in this trial within
             the last 5 years with the exception of basal or squamous cell carcinoma of the skin OR
             curatively treat in situ disease.

          -  Autoimmune disease requiring systemic treatment (e.g., with disease modifying agents,
             corticosteroids, or immunosuppressive drugs) in the past 2 years. Hormone replacement
             therapy (e.g., insulin, thyroxine, and replacement-dose hydrocortisone) is not
             considered systemic treatment.

          -  Active or prior paraneoplastic neurologic disorder of the central nervous system (CNS)

          -  Prior allograft

          -  Clinically significant cardiovascular disease, e.g., cerebral vascular accident/stroke
             or myocardial infarction, within 6 months prior to the first dose of investigational
             product, unstable angina, congestive heart failure (New York Heart Association ≥ Class
             III), or unstable cardiac arrhythmia requiring medication

          -  Presence of active, symptomatic, or untreated CNS metastasis; or CNS metastasis that
             requires local directed therapy or increasing doses of corticosteroids within the 2
             weeks prior to the planned first dose of investigational product. Individuals with
             treated and/or asymptomatic CNS disease may be enrolled if neurologically stable over
             the prior 2 weeks (and after consultation with the Medical Monitor)

          -  HIV infection with an AIDS-defining opportunistic infection within the past 12 months
             or with a CD4+ T cell count <350/µL

          -  Hepatitis B surface antigen (HBsAg) positive OR anti-Hepatitis B core (anti-HBc)
             positive and HBV viral load above the lower limit of quantification

          -  Hepatitis C antibody positive with HCV viral load greater than or equal to the lower
             limit of quantification

          -  Infection requiring intravenous antibacterial, antiviral, or antifungal therapy within
             2 weeks prior to the planned first dose of investigational product

          -  Ongoing ≥ Grade 2 toxicity(ies) due to a previously administered anticancer agent with
             the following exceptions:

               1. Grade 2 neuropathy or alopecia

               2. For the monotherapy cohorts: Grade 2 immune-related endocrinopathy attributed to
                  a checkpoint inhibitor and controlled with hormone replacement alone

          -  Treatment with biological agents (including monoclonal antibodies) within 28 days of
             the planned first dose of investigational product with the following exception:

             a. For the pembrolizumab combination therapy cohort: Pembrolizumab treatment within 28
             days of the planned first dose of investigational product.

          -  Treatment with radiation, chemotherapy or anticancer small molecule therapy within 14
             days or 5 half-lives (whichever is longer) prior to the planned first dose of
             investigational product. Treatment with nitrosoureas or mitomycin C require a 42-day
             washout prior to the planned first dose of investigational product

          -  Receipt of any investigational drug or device not otherwise specified above within 28
             days or 5 half-lives (whichever is longer) prior to the planned first dose of
             investigational product

          -  Pregnant or breastfeeding; negative pregnancy status in WOCBP must be confirmed by
             serum pregnancy test at Screening

          -  History of ≥ Grade 3 infusion-related reaction associated with antibody
             administration; or:

               1. For the monotherapy cohorts: Known allergy/intolerance to ATRC-101 or its
                  excipients

               2. For the pembrolizumab combination therapy cohort: Known allergy/intolerance to
                  ATRC 101, pembrolizumab, or their excipients

          -  Major surgery or significant traumatic injury occurring within 28 days prior to the
             planned first dose of investigational product. If major surgery occurred > 28 days
             prior to Cycle 1-Day 1, individual must have recovered adequately from the toxicity
             and/or complications from the intervention prior to Cycle 1-Day 1

          -  Prior treatment with ATRC-101

          -  Intercurrent illness that is either life-threatening or of clinical significance such
             that it might limit compliance with trial requirements, or in the Investigator's
             assessment would place the participant at an unacceptable risk for participation.

          -  Receipt of a live vaccine within 30 days of planned Cycle 1-Day 1. Examples of live
             vaccines include, but are not limited to, the following: measles, mumps, rubella,
             varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG),
             and typhoid vaccine. Seasonal influenza vaccines for injection are generally
             inactivated flu vaccines and are allowed. Intranasal influenza vaccines (e.g. FluMist)
             are live attenuated vaccines and are not allowed.

        For the pembrolizumab combination therapy cohort ONLY:

          -  Experienced ≥ Grade 3 or higher immune related adverse events while on immunotherapy
             prior to enrollment

          -  Have not recovered from ≥ Grade 2 immune related adverse events attributed to
             immunotherapy prior to enrollment.

          -  NSCLC with epidermal growth factor receptor (EGFR) or anaplastic lymphoma receptor
             tyrosine kinase (ALK) genomic tumor alterations

          -  Isolated intracranial relapse

          -  Interstitial lung disease or active, non-infectious pneumonitis

          -  Signs and symptoms consistent with clinically significant, decreased pulmonary
             function: (1) blood saturation oxygen level (SpO2) < 90% at rest on room air; (2)
             dyspnea at rest (CTCAE ≥ Grade 3) or required supplemental oxygenation within 14 days
             prior to the planned first dose of investigational product

          -  Ongoing immune-related toxicity or immune-related toxicity at any time requiring
             systemic corticosteroids
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Jonathan Benjamin, MD, PhD, 650-453-5279, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT04244552

Organization ID

ATRC-101-A01


Responsible Party

Sponsor

Study Sponsor

Atreca, Inc.


Study Sponsor

Jonathan Benjamin, MD, PhD, Study Director, Atreca, Inc.


Verification Date

May 2021