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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.
Full 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.
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Inclusion and exclusion criteria
Selected Inclusion Criteria:
Part 2 includes but is not limited to:
Cutaneous melanoma that is either locally unresectable or metastatic:
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
Patients must have no more than 1 prior line of systemic therapy for unresectable locally advanced or metastatic disease. Neo-adjuvant and adjuvant therapy do not count as a prior line of therapy
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
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:
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
Primary purpose
Allocation
Interventional model
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159 participants in 5 patient groups
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Central trial contact
Jim Vasselli, MD
Data sourced from clinicaltrials.gov
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