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

Plain English Summary

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 is a Phase 2 clinical trial sponsored by Aulos Bioscience, Inc. studying Advanced Solid Tumor, Metastatic Cancer, Cutaneous Melanoma, Non-Small Cell Lung Cancer. This trial tests a new drug called AU-007, which is a type of antibody designed to fight cancer. It is for adults with advanced or metastatic cancer, including specific types of melanoma and lung cancer, who have not responded to other treatments. Participants will receive AU-007 alone or with other cancer drugs, and will have regular check-ups to monitor their health and the drug's effects. Alternative treatments may include other immunotherapies, chemotherapy, or targeted therapies, depending on the specific cancer type and previous treatments. The trial aims to enroll 159 participants.

Official Summary

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 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults with advanced or metastatic melanoma or non-small cell lung cancer that has stopped responding to other treatments. Patients must have measurable disease and meet specific criteria related to prior treatments and lab results. Individuals with certain autoimmune diseases, recent major surgery, or active brain metastases may not be eligible. Women of childbearing potential and men with partners of childbearing potential must agree to use effective contraception during the study. This trial is studying Advanced Solid Tumor, Metastatic Cancer, Cutaneous Melanoma, Non-Small Cell Lung Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcomes measure how safe and well-tolerated the new drug AU-007 is, and to determine the best dose to use in future studies, which is crucial for patient safety and treatment effectivenes The specific primary outcome measures are: Evaluate the safety and tolerability of AU-007 (Day 1 thru end of treatment (EOT) visit (28 days after last dose)); Establish the maximum tolerated dose (MTD) and/or RP2D (Day 1 thru EOT visit (28 days after last dose)). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial is important because it explores a novel approach to cancer treatment by targeting the immune system's interaction with cancer cells, potentially filling a gap for patients with limited opt Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Advanced Solid Tumor, Metastatic Cancer, Cutaneous Melanoma, Non-Small Cell Lung Cancer, where improved treatment options are needed.

Investor Insight

This Phase 1/2 trial represents an early-stage investment in a novel immunotherapy for advanced cancers, a significant market, with potential for high returns if successful, though early-stage trials Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of AU-007, and how it compares to other available treatments. Understand the schedule of visits, tests, and procedures involved in the trial, and how the study drug will be administered. Be prepared for regular blood tests and imaging scans to monitor your health and the cancer's response to treatment. This trial is currently recruiting participants. The trial is being conducted at 18 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 159 participants

Interventions

• DRUG: AU-007 — Monoclonal Antibody Targeting IL-2
• DRUG: Aldesleukin — IL-2
• DRUG: Avelumab — Monoclonal Antibody Targeting PD-L1
• DRUG: Nivolumab — Monoclonal Antibody Targeting PD-1

Primary Outcomes

• Evaluate the safety and tolerability of AU-007 (Day 1 thru end of treatment (EOT) visit (28 days after last dose))
• Establish the maximum tolerated dose (MTD) and/or RP2D (Day 1 thru EOT visit (28 days after last dose))

Secondary Outcomes

• Magnitude of PK changes in the blood after dosing determined by area under the curve (AUC) of AU-007 (Day 1 thru EOT visit (28 days after last dose))
• Magnitude of PK changes in the blood after dosing determined by maximum concentration (Cmax) of AU-007 (Day 1 thru EOT visit (28 days after last dose))
• Magnitude of PK changes in the blood after dosing determined by time of maximum concentration (Tmax) (Day 1 thru EOT visit (28 days after last dose))
• Magnitude of PK changes in the blood after dosing determined by Half-life (T1/2) of AU-007 (Day 1 thru EOT visit (28 days after last dose))
• Magnitude of cytokine changes in the blood after dosing (Day 1 thru EOT visit (28 days after last dose))

Full 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 wh

Trial Locations

• Sylvester Comprehensive Cancer Center - Miami, Miami, Florida, United States
• START Midwest, Grand Rapids, Michigan, United States
• Minnesota Oncology and Hematology PA, Minneapolis, Minnesota, United States
• Washington University, St Louis, Missouri, United States
• Atlantic Healthcare System, Morristown, New Jersey, United States
• Carolina Biooncology Institute, Huntersville, North Carolina, United States
• Sarah Cannon Research Institute, Nashville, Tennessee, United States
• Texas Oncology (Balcones) - SCRI, Austin, Texas, United States
• MD Anderson Cancer Center, Houston, Texas, United States
• START South Texas Accelerated Research Therapeutics, San Antonio, Texas, United States
• ...and 8 more locations

Frequently Asked Questions

Related Conditions

• Advanced Solid Tumor
• Metastatic Cancer
• Cutaneous Melanoma
• Non-Small Cell Lung Cancer
• Immunotherapy
• Monoclonal Antibodies
• IL-2 Pathway
• PD-1 Inhibitors
• PD-L1 Inhibitors
• CTLA-4 Inhibitors

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