RecruitingPhase 1 / Phase 2

Study of AU-007, A Monoclonal Antibody That Binds to IL-2 and Inhibits IL-2Rα Binding, in Patients With Unresectable Locally Advanced or Metastatic Cancer

A Phase 1/2, First-in-Human, Open Label, Dose Escalation and Expansion Study of AU-007, A Monoclonal Antibody That Binds to IL-2 and Inhibits IL-2Rα Binding, in Patients With Unresectable Locally Advanced or Metastatic Cancer

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years and older
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

Not stated in the study description — ask the study team about visits and procedures.

Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests AU-007, also called imneskibart, alone or with other drugs in people with advanced solid tumors that cannot be removed by surgery or have spread. Researchers want to learn how safe it is, how well people handle it, and whether it helps treat cancer. This is the first study of AU-007 in humans.

This is a first in human, open-label, multi-center Phase 1 / 2 study to evaluate the safety, tolerability, and initial efficacy of AU-007, also known as imneskibart, in patients with advanced solid tumors. AU-007 will be administered either as a monotherapy, or in combination with a single loading dose of aldesleukin, or with both AU-007 and aldesleukin given every 2 weeks (Q2w). Once the recommended phase 2 dose (RP2D) of AU-007 plus aldesleukin was determined, (AU-007 Q2w plus a single loading dose of aldesleukin), AU-007 plus aldesleukin is also being administered with avelumab or nivolumab.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • You must have cancer that can be measured on a CT or MRI scan.
  • Some study groups include skin melanoma that cannot be removed by surgery or has spread. Prior treatment and BRAF gene rules vary by group.
  • For the listed melanoma groups, cancer must have grown after at least 2 cycles of certain two-drug immune treatments. Scans must show growth at least 4 weeks before treatment, unless the study doctor allows an exception. LDH, a blood marker, must be no more than 2.5 times the normal upper limit.
  • The listed lung cancer groups require advanced non-small cell lung cancer with PD-L1 in at least 1% of tumor cells, no activating EGFR gene change or ALK rearrangement, and cancer growth during or after certain immune treatments.
  • If you can become pregnant, you need a negative pregnancy test within 72 hours before treatment. Use 2 birth control methods through 60 days after treatment, or 5 months if receiving nivolumab. Not having sex is allowed if it is your usual, preferred method.
  • Men with partners who can become pregnant must use barrier birth control and not donate sperm from consent through 60 days after treatment ends. Their partners must also use birth control during this time.
  • Side effects from past immune checkpoint drugs must be mild or back to their level before treatment. An underactive thyroid is allowed if well controlled with thyroid medicine.
  • Cancer spread to the brain or spinal cord that caused symptoms must be treated and symptom-free for at least 14 days. There must be no ongoing treatment for it, cancer in the surrounding lining, or pressure on the spinal cord.

Who can't join

  • Most autoimmune diseases, where the immune system attacks the body. Exceptions include certain skin conditions, hair loss, controlled thyroid conditions, and arthritis needing no body-wide treatment beyond oral anti-inflammatory pain medicines.
  • Major surgery or a serious injury within 3 weeks before AU-007, or wounds from surgery or injury that have not healed.
  • More than 10 mg of prednisone daily, or similar steroids or other immune-suppressing drugs, within 7 days before treatment. Steroids used on skin, in eyes, by inhaler, or in the nose are allowed.
  • Side effects from past cancer drugs that have not returned to their starting level, or side effects from radiation that have not resolved.
  • Serious side effects from past IL-2 treatment, such as a hole in the bowel, digestive tract bleeding, abnormal heartbeat, heart attack, or repeated seizures.
  • Inflammation that has not been resolved for at least 4 weeks before treatment. Ongoing mild inflammation, such as lung inflammation caused by radiation, also excludes you.
  • A second invasive cancer that has not been in remission for at least 1 year. Exceptions include certain skin, cervical, and localized prostate cancers, removed early melanoma, and some slow-growing cancers that never needed treatment. Slow-growing lymphomas are not an exception.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

Selected Inclusion Criteria: * Patients must have measurable disease as per RECIST v1.1 criteria and documented by CT and/or MRI * Part 2 includes but is not limited to: * Cutaneous melanoma that is either locally unresectable or metastatic: * BRAF wild type: progressed after receiving PD-1 containing therapy with or without an anti-CTLA-4 * BRAF mutation: patients who refused BRAF+MEK inhibitor * Must have objective progression after receiving at least two cycles of prior doublet therapy (anti-PD-1/anti-CTLA-4 or anti-PD-1/anti-LAG-3) * Radiographic progression ≥ 4 weeks prior to the first dose of study drug to rule out late response to most recent therapy. The requirement for documented radiologic progression may be waived after review by Medical Monitor (e.g., in the case of progression beyond 12 weeks after starting a doublet) * LDH ≤ 2.5 x ULN * NSCLC: Unresectable locally advanced or metastatic PD-L1-positive (tumor proportion score \[TPS\] ≥ 1%) NSCLC not harboring an activating EGFR mutation or ALK rearrangement and has progressed during or following treatment with an anti-PDx with or without platinum-based chemotherapy * Part 3: NSCLC as described above * Part 4: cutaneous melanoma * Unresectable locally advanced or metastatic cutaneous melanoma that has progressed during or following treatment with an anti-PDx (unless ineligible for anti-PDx therapy) * Patients with BRAF mutations must either be ineligible for or have refused a BRAF+MEK inhibitor * Must have objective progression after receiving at least two cycles of prior doublet therapy (anti-PD-1/anti-CTLA-4 or anti-PD-1/anti-LAG-3). * Radiographic progression ≥ 4 weeks prior to the first dose of study drug to rule out late response to most recent therapy. The requirement for documented radiologic progression may be waived after review by Medical Monitor (e.g., in the case of progression beyond 12 weeks after starting a doublet) * LDH ≤ 2.5 x ULN * Female patients of childbearing potential must have a negative serum or urine pregnancy test performed within 72 hours prior to the initiation of study drug administration. Female patients of childbearing potential must be willing to use two forms of contraception throughout the study, starting with Screening through 60 days after the last dose of study drug (or 5 months after the last dose of study drug for patients receiving nivolumab). Abstinence is acceptable if this is the established and the preferred contraception method for the patient * Male patients with partners of childbearing potential must use barrier contraception from the time of consent through 60 days after discontinuation of study drug and must not donate sperm during this period. In addition, male patients should have their partners use contraception (as documented for female patients) for the same period of time * Patients who have previously received an immune checkpoint inhibitor (e.g., anti-PD-L1, anti-PD-1, anti-CTLA-4) prior to enrollment must have checkpoint inhibitor immune-related toxicity resolved to either Grade ≤ 1 or baseline (prior to the checkpoint inhibitor) to be eligible for enrollment. Patients who experienced previous checkpoint inhibitor-related hypothyroidism are eligible for the study regardless of grade resolution if well controlled on thyroid hormone replacement therapy * Symptomatic central nervous system (CNS) metastases must have been treated, be asymptomatic for ≥ 14 days, and meet the following at the time of enrollment: * No concurrent treatment for CNS disease (e.g., surgery, radiation, corticosteroids ≥ 10 mg prednisone/day or equivalent) * No concurrent leptomeningeal disease or cord compression Exclusion Criteria: * Patients with a history of known autoimmune disease with exceptions of * Vitiligo * Psoriasis, atopic dermatitis, or other autoimmune skin condition not requiring systemic treatment * History of Graves' disease in patients now euthyroid for \> 4 weeks * Hypothyroidism managed by thyroid hormone replacement * Alopecia * Arthritis managed without systemic therapy beyond oral nonsteroidal anti- inflammatory drugs * Major surgery or traumatic injury within 3 weeks before first dose of AU-007 * Unhealed wounds from surgery or injury * Treatment with \> 10 mg per day of prednisone (or equivalent) or other immune-suppressive drugs within the 7 days prior to the initiation of study drug. Steroids for topical, ophthalmic, inhaled, or nasal administration are allowed * Prior anti-cancer therapy before the planned start of AU-007 as follows: * Not recovered to baseline from toxicity of prior systemic cancer therapy(ies). * Not recovered from toxicity of radiotherapy. * Concurrent use of hormones either to maintain castrate levels of testosterone in patients with castration-sensitive prostate cancer or for non-cancer-related conditions (e.g., insulin for diabetes, hormone replacement therapy) is acceptable. Bisphosphonates are permitted. * Patients who have experienced serious adverse events during prior IL-2 therapy (including but not limited to bowel perforation, gastrointestinal bleeding, arrythmias, myocardial infarction, repetitive seizures). * Inflammatory process that has not resolved for ≥ 4 weeks from the date of first study dose. Patients with chronic low-grade inflammatory processes such as radiation-induced pneumonitis are excluded regardless of duration * Second primary invasive malignancy not in remission for ≥ 1 year. Exceptions include non-melanoma locally advanced skin cancer, cervical carcinoma in situ, localized prostate cancer (Gleason score ≤ 7), resected melanoma in situ, or any malignancy considered to be indolent and never required therapy, with the exception of indolent lymphomas

Study sites (10)

FL

MI

MN

MO

NC

TN

TX

UT