This is a Phase IIb, single-arm, multicohort, open-label multicenter study of ALT-803 in combination with an FDA-approved PD-1/PD-L1 checkpoint inhibitor in patients with advanced cancers who have progressed following an initial response to treatment with PD-1/PD-L1 checkpoint inhibitor therapy. All patients will receive the combination treatment of PD-1/PD-L1 checkpoint inhibitor plus ALT-803 for up to 16 cycles. Each cycle is six weeks in duration. All patients will receive ALT-803 once every 3 weeks. Patients will also receive the same checkpoint inhibitor that they received during their previous therapy. Radiologic evaluation will occur at the end of each treatment cycle. Treatment will continue for up to 2 years, or until the patient experiences confirmed progressive disease or unacceptable toxicity, withdraws consent, or if the Investigator feels it is no longer in the patient's best interest to continue treatment. Patients will be followed for disease progression, post-therapies, and survival through 24 months past administration of the first dose of study drug.
Name: ALT-803 + Pembrolizumab
Name: ALT-803 + Nivolumab
Name: ALT-803 + Atezolizumab
Name: ALT-803 + Avelumab
Description: Assess the anti-tumor activity of ALT-803 in combination with a PD-1/PD-L1 checkpoint inhibitor in patients with advanced cancers who have progressed following an initial response to treatment with PD-1/PD-L1 checkpoint inhibitors.
Measure: Objective Response Rate Time: 24 monthsDescription: Assess time from first treatment to death resulting from cancer.
Measure: Disease-specific Survival Time: 24 monthsDescription: Assess time from first treatment to death resulting from any cause.
Measure: Overall Survival Time: 24 monthsDescription: Assess time to response
Measure: Time to Response Time: 24 monthsDescription: Assess duration of response
Measure: Duration of Response Time: 24 monthsDescription: Assess incidence of adverse events.
Measure: Incidence of Adverse Events Time: 24 monthsDescription: Compare changes in QOL scores from baseline.
Measure: Quality of Life (QOL) Time: 24 monthsDescription: Assess amount of time disease does not get worse after first treatment.
Measure: Progression-free Survival Time: 24 monthsAllocation: Non-Randomized
Parallel Assignment
There is one SNP
Patients with BRAF V600E mutation-positive melanoma were not required to have received prior BRAF inhibitor therapy; OR unresectable or metastatic melanoma with progression, refractory to ≥ 2 doses of ipilimumab (3 mg/kg or higher) and, if BRAF V600 mutation-positive, a BRAF or MEK inhibitor, and disease progression within 24 weeks following the last dose of ipilimumab. --- V600E ---