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
Overview
- Phase
- Phase 1
- Intervention
- Aldesleukin
- Conditions
- Not specified
- Sponsor
- Aulos Bioscience, Inc.
- Enrollment
- 159
- Locations
- 31
- Primary Endpoint
- Evaluate the safety and tolerability of AU-007
- Status
- Recruiting
- Last Updated
- 2 months ago
Overview
Brief 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.
Detailed Description
This is a first in human, multicenter, open-label Phase 1-2 study evaluating the safety, tolerability, and initial efficacy of AU-007 with or without aldesleukin, in patients with unresectable locally advanced or metastatic cancer. Patients must either be ineligible for or have progressed on prior standard of care therapy. Part 1 consists of 3 escalation Arms, each starting with a single 1+2 escalation cohort followed by 3+3 escalation cohorts to define the RP2D or maximum tolerated dose (MTD). The study begins in Arm A evaluating escalating doses of AU-007 (Q2w) in sequential escalation cohorts to define RP2D or MTD. In Arm B, AU-007 (Q2w) is evaluated in combination with a single dose of aldesleukin given with the first AU-007 dose. AU-007 is administered Q2w with an escalating single aldesleukin dose in sequential escalation cohorts. In Arm C, AU-007 is evaluated in combination with aldesleukin, both given Q2w. AU-007 will be administered with an escalating dose of aldesleukin in each sequential Arm C escalation cohort. The Part 2 cohort expansion portion of the study consists of up to three expansion Arms evaluating the initial efficacy of the RP2D (AU-007 plus a single loading dose of aldesleukin) in selected solid tumor types, prioritizing cutaneous melanoma and non-small cell lung cancer (NSCLC). Part 3 evaluates the safety of AU-007 in combination with aldesleukin and avelumab, followed by one expansion cohort, in NSCLC. Part 4 evaluates the safety of AU-007 plus aldesleukin in combination with nivolumab, followed by one expansion cohort, in cutaneous melanoma.
Investigators
Eligibility Criteria
Inclusion 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
Exclusion Criteria
- •Patients with a history of known autoimmune disease with exceptions of
- •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
- •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).
Arms & Interventions
AU-007 plus aldesleukin in combination with nivolumab
AU-007 (Q2w) administered in combination with a single dose of aldesleukin with the initial AU-007 dose. Nivolumab will be administered Q4w.
Intervention: Aldesleukin
AU-007 Monotherapy
AU-007 (Q2w) administered as a monotherapy sequential ascending doses with each Dose Escalation Cohort (Complete; no longer enrolling)
Intervention: AU-007
AU-007 combined with a single dose of aldesleukin
AU-007 (Q2w) administered in combination with a single dose of aldesleukin with the initial AU-007 dose.
Intervention: AU-007
AU-007 combined with a single dose of aldesleukin
AU-007 (Q2w) administered in combination with a single dose of aldesleukin with the initial AU-007 dose.
Intervention: Aldesleukin
AU-007 combined with aldesleukin given concomitantly
AU-007 administered in combination with aldesleukin, both administered Q2w (Complete; no longer enrolling)
Intervention: AU-007
AU-007 combined with aldesleukin given concomitantly
AU-007 administered in combination with aldesleukin, both administered Q2w (Complete; no longer enrolling)
Intervention: Aldesleukin
AU-007 plus aldesleukin in combination avelumab
AU-007 and avelumab administered Q2w with a single dose of aldesleukin with the initial AU-007 dose
Intervention: AU-007
AU-007 plus aldesleukin in combination avelumab
AU-007 and avelumab administered Q2w with a single dose of aldesleukin with the initial AU-007 dose
Intervention: Aldesleukin
AU-007 plus aldesleukin in combination avelumab
AU-007 and avelumab administered Q2w with a single dose of aldesleukin with the initial AU-007 dose
Intervention: Avelumab
AU-007 plus aldesleukin in combination with nivolumab
AU-007 (Q2w) administered in combination with a single dose of aldesleukin with the initial AU-007 dose. Nivolumab will be administered Q4w.
Intervention: AU-007
AU-007 plus aldesleukin in combination with nivolumab
AU-007 (Q2w) administered in combination with a single dose of aldesleukin with the initial AU-007 dose. Nivolumab will be administered Q4w.
Intervention: Nivolumab
Outcomes
Primary Outcomes
Evaluate the safety and tolerability of AU-007
Time Frame: Day 1 thru end of treatment (EOT) visit (28 days after last dose)
Measured by the frequency of DLTs (Dose limiting toxicity) and safety profile
Establish the maximum tolerated dose (MTD) and/or RP2D
Time Frame: Day 1 thru EOT visit (28 days after last dose)
With AU-007 alone or in combination with aldesleukin measured by pharmacokinetics (PK), pharmacodynamics (PD), and Biomarkers
Secondary Outcomes
- Magnitude of immunogenicity after dosing with AU-007 alone or in combination with aldesleukin, AU-007 in combination with aldesleukin and avelumab or nivolumab(Day 1 thru EOT visit (28 days after last dose))
- 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))
- Evaluate the preliminary anti-tumor activity of AU-007 alone, in combination with aldesleukin, in combination with aldesleukin and avelumab, and AU-007 plus aldesleukin with nivolumab in patients with unresectable locally advanced or metastatic cancer(Day 1 thru EOT visit (28 days after last dose))