Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication ANKTIVA in combination with Bacillus Calmette-Guérin (BCG) is indicated for the treatment of adult patients with BCG-unresponsive nonmuscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. FDA label
Also known as N-803 (Cohort 2 part B), N-803, ALT-803, Nogapendekin Alfa Inbakicept (NAI), Anktiva, N-803 (IL-15 Superagonist), NAI
Nogapendekin alfa inbakicept · 21 trials · 42 indications
Proportion of participants who die from any cause by Day 28 after the first dose of study treatment.
Progression-free survival (PFS) as assessed by RECIST 1.1 criteria comparing the experimental treatment arm with the standard-of-care control arm in participants with locally advanced HPV-positive oropharyngeal squamous cell carcinoma (OPSCC).
Evaluate efficacy of experimental therapies with a) intravesical N-803 plus BCG or b) intravesical N-803 plus gemcitabine by CR rate at month 3 or month 6 (for re-inducted participants) in participants with intermediate-risk NMIBC.
Measured by RECIST v1.1 and iRECIST
Measured by RECIST v1.1 and iRECIST
Measured by RECIST v1.1 and iRECIST
Measured by RECIST v1.1 and iRECIST
Measured by RECIST v1.1 and iRECIST and survival status
Measured by the CA-125 result
Response Criteria in Solid Tumors (RECIST) V1.1
ORR reflects tumor shrinkage and is the key measure of antitumor activity.
OS is the gold-standard efficacy endpoint; the protocol explores whether an ALC rise predicts a survival benefit.
Cohort A \& Cohort C: Assess incidence of complete response of CIS (with or without Ta/T1 papillary disease) patients at any time
Cohort B: Assess disease-free rate at 12 months since first study treatment
-LFS is defined as the time from achievement of complete remission (CR) to the time of relapse, death in remission, or last follow-up.
determination of a dose level for the phase 2 study (RP2D)
determination of a dose level for the phase 2 study (RP2D)
A continual reassessment method (CRM) design will be used to identify the maximum tolerated dose (MTD) for Phase Ib patients
The phase II portion of the study looks to define the objective response rate (using immune-related RECIST) of ALT-803 added to nivolumab in patients with advanced and unresectable non-small cell lung cancer. Objective response rate will be defined by the best overall response, which is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease, the smallest measurements recorded since the treatment started). The subject's best response assignment will depend on the achievement of both measurement and confirmation criteria.
The proportion of participants with treatment-emergent adverse events (TEAEs), as graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 6.0.
Percentage of participants alive and progression free at 12 months, defined as the time from the date of first dose of study drugs (C1D1) to the date of disease progression or death (any cause), whichever occurs first, by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
As assessed via CTCAE v6.0. Dose limiting toxicities will be evaluated according to protocol.
RP2D is defined as the highest dose of N-803 that has an overall DLT rate of less than 33% in total of 6 patients.
PFS is defined as the duration of time from the start date of study treatment to the date of earliest progression or death, whichever occurs first. Patients who neither progress nor die by the data cutoff date will be censored at the last follow up date.
DLTs are defined in the protocol.
Safety of CD19 t-haNK will be assessed by incidence and severity of TEAEs and SAEs, as well as incidence of clinically significant in safety laboratory tests and vital signs
Determine the maximum tolerated dose (MTD) level and designate the recommended dose level for phase II.
Number and severity of treatment related adverse events (AEs) that occur or worsen after the first dose of study treatment
Determine the 8.5 month overall survival of treated patients
Patients in Cohort A: compare complete response rate between treatment arms using cystoscopy, confirmatory bladder biopsy and urine cytology.
Patients in Cohort B: compare disease-free survival between treatment arms using cystoscopy, confirmatory bladder biopsy and urine cytology.
The safety endpoint is the MTD of ALT-803, defined as the dose level below that at which ≥2 of 6 patients experience a DLT.
| Arm | Type | Description |
|---|---|---|
| Cohort A: Experimental Arm | EXPERIMENTAL | 3-week cycles. N803, Tislelizumab, and Docetaxel will be administered on Cycle 1 and 2. N803 and Tislelizumab will be administered on Cycle 3 and onward until end of study. |
| Cohort A: Control Arm | ACTIVE_COMPARATOR | The control arm treatment regimen will consist of repeated 3-week cycles with a ± 3-day window for each visit of Docetaxel 75 mg/m2 IV. |
| Cohort B: Experimental Arm | EXPERIMENTAL | 3-week cycles. N803, prior failed checkpoint inhibitor, and Docetaxel will be administered on Cycle 1 and 2. N803 and prior failed checkpoint inhibitor will be administered on Cycle 3 and onward until end of study. |
| Cohort B: Control Arm | ACTIVE_COMPARATOR | The control arm treatment regimen will consist of repeated 3-week cycles with a ± 3-day window for each visit of Docetaxel 75 mg/m2 IV. |
| NAI Plus Standard of Care | EXPERIMENTAL | Participants receive NAI 1.2 mg subcutaneously plus protocol-defined standard of care. |
| Placebo plus standard of care | PLACEBO_COMPARATOR | Participants receive matching placebo subcutaneously plus protocol-defined standard of care. |
| Phase 2a, Single Arm (Safety Lead-In) | EXPERIMENTAL | Participants will receive neoadjuvant nogapendekin alfa inbakicept (NAI), hAd5-HPV vaccine (IBRX-042), and nab-paclitaxel followed by de-intensified intensity-modulated radiation therapy (IMRT) with concurrent cisplatin, and post-radiation NAI and IBRX-042 during the Phase 2a safety lead-in portion of the study. |
| Arm A | EXPERIMENTAL | Participants will receive neoadjuvant nogapendekin alfa inbakicept (NAI), hAd5-HPV vaccine (IBRX-042), and nab-paclitaxel followed by de-intensified intensity-modulated radiation therapy (IMRT) with concurrent cisplatin, and post-radiation NAI and IBRX-042. |
| Arm B | ACTIVE_COMPARATOR | Participants will receive standard-of-care intensity-modulated radiation therapy (IMRT) with concurrent cisplatin for locally advanced HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). |
| NAI + Standard of Care | EXPERIMENTAL | NAI 1.2 mg subcutaneous injection administered on Days 3 (or earlier if ALC \<700 cells/µL), Day 14, and Day 21 if needed for ALC \<1,000 cells/µL, plus institutional standard of care for sepsis |
| Standard of Care Alone | ACTIVE_COMPARATOR | Institutional standard of care for sepsis including antimicrobial therapy, fluid resuscitation, vasopressor support, and mechanical ventilation as clinically indicated |
| N-803 | EXPERIMENTAL | All patients will be in this arm. |
| N-803 and BCG | EXPERIMENTAL | Combination treatment of 1) N-803 (400 μg): Weekly for 6 weeks (induction, re-induction); Monthly from month 3 through month 15 (maintenance) and 2) BCG (50mg): Weekly for 6 weeks (induction, re-induction) |
| N-803 and Gemcitabine | EXPERIMENTAL | Combination treatment of 1) N-803 (400 μg): Weekly for 6 weeks (induction, re-induction); Monthly from month 3 through month 15 (maintenance) and 2) Gemcitabine (2000mg): Weekly for 6 weeks (induction, re-induction) |
| All subjects | EXPERIMENTAL | Gemcitabine plus M-CENK plus N-803 |
| Cohort A Control Treatment Arm | ACTIVE_COMPARATOR | SBRT + gemcitabine + nab-paclitaxel |
| Cohort A Experimental Treatment Arm 1 | EXPERIMENTAL | SBRT + cyclophosphamide + gemcitabine + nab-paclitaxel + aldoxorubicin HCl + N-803 |
| Cohort A Experimental Treatment Arm 2 | EXPERIMENTAL | SBRT + cyclophosphamide + gemcitabine + nab-paclitaxel+ aldoxorubicin HCl + N-803 + PD-L1 t-haNK |
| Cohort B Control Treatment Arm | ACTIVE_COMPARATOR | Irinotecan liposome + 5-FU/leucovorin |
| Cohort B Experimental Treatment Arm | EXPERIMENTAL | SBRT + cyclophosphamide + gemcitabine + nab-paclitaxel+ aldoxorubicin HCl + N-803 + PD-L1 t-haNK |
| Cohort C Experimental Treatment Arm | EXPERIMENTAL | SBRT + cyclophosphamide + gemcitabine + nab-paclitaxel + aldoxorubicin + N-803 + PD-L1 t-haNK |
| Cohort 1 | OTHER | Patients with any of the cancers listed below who have progressed on or after single-agent checkpoint inhibitor therapy after experiencing an initial complete response (CR) or partial response (PR) while taking a checkpoint inhibitor. 1a - Non-small cell lung cancer 1b - Small cell lung cancer 1c - Urothelial carcinoma 1d - Head and neck squamous cell carcinoma 1e - Merkel cell carcinoma 1f - Melanoma 1g - Renal cell carcinoma 1h - Gastric cancer 1i - Cervical cancer 1j - Hepatocellular carcinoma 1k - Microsatellite instability-high or mismatch repair deficient solid tumor cancer or colorectal cancer |
| Cohort 2 | OTHER | Patients with NSCLC whose tumors have high PD-L1 expression (TPS ≥ 50%) and who relapsed on a PD-1 checkpoint inhibitor after experiencing an initial CR or PR when they received checkpoint inhibitor as a single-agent for first-line treatment. |
| Cohort 3 | OTHER | Patients with NSCLC who had an initial CR or PR but subsequently relapsed on maintenance PD-1 checkpoint inhibitor therapy when they initially received checkpoint inhibitor therapy in combination with chemotherapy as first-line treatment. |
| Cohort 4 | EXPERIMENTAL | Patients who are currently receiving PD-1/PD-L1 checkpoint inhibitor therapy and have disease progression after experiencing stable disease (SD) for at least 6 months during their previous treatment with PD-1/PD-L1 checkpoint inhibitor therapy. |
| Cohort 5 | EXPERIMENTAL | Patients that have experienced disease progression by Investigator-assessment per irRECIST while receiving treatment in Cohorts 1-4. |
| Cohort 6 | EXPERIMENTAL | Patients who have progressed after an initial response (CR or PR) to a PD-1/PD-L1 checkpoint inhibitor but now exhibit acquired resistance. They have received exactly one line of anti-PD-1 or anti-PD-L1 therapy (either pembrolizumab or nivolumab) for advanced NSCLC (Stage IV or recurrent). |
| BCG+N-803 | EXPERIMENTAL | - |
| Recipient | EXPERIMENTAL | * Standard of care reduced conditioning regimen on Day -1 * Graft cell infusion on Day 0 * Post-transplant cyclophosphamide on Days +3 and +4 * GvHD prophylaxis with tacrolimus and mycophenolate mofetil (MMF) will start on Day +5. MMF will continue till Day +35 and tacrolimus till Day +180 in the absence of GvHD * G-CSF will start on Day +7 and will continue until neutrophil engraftment as per institutional guidelines * The cytokine-induced memory like natural killer (CIML NK) cells will be infused on Day +7 without a filter or pump, slowly by gravity over at least 15 minutes. * ALT-803 will start approximately 4 hours after the CIML NK cell infusion. ALT-803 will be administered subcutaneously at a dose of 10 mcg/kg subcutaneously beginning Day +7 (on the day of CIML NK cell infusion) and then every 21 days for a total of 4 doses |
| Donor | EXPERIMENTAL | * Donors will receive subcutaneous G-CSF from Day -4 till Day 0 and undergo 20L apheresis per institutional guidelines. * Two consecutive days for collection are allowed in case of the target CD34+ cell dose being less than the target 4 x106/kg-bw from the first day of collection. * On Day +6 (one day before the planned CIML NK cell infusion), peripheral blood mononuclear cells will be collected by a single standard 20-L apheresis over 4-5 hours from the same haploidentical related donor that provided the HCT graft. |
| Cohort 1: ALT-803 6 µg/kg + Nivolumab 3 mg/kg | EXPERIMENTAL | Participants receive ALT-803 6 µg/kg + Nivolumab 3 mg/kg IV per protocol |
| Cohort 2: ALT-803 10 µg/kg + Nivolumab 3 mg/kg | EXPERIMENTAL | Participants receive ALT-803 10 µg/kg + Nivolumab 3 mg/kg IV per protocol |
| Cohort 3: ALT-803 15 µg/kg + Nivolumab 3 mg/kg | EXPERIMENTAL | Participants receive ALT-803 15 µg/kg + Nivolumab 3 mg/kg IV per protocol |
| Cohort 4: ALT-803 20 µg/kg + Nivolumab 3 mg/kg (RP2D) | EXPERIMENTAL | Participants receive ALT-803 20 µg/kg + Nivolumab 3 mg/kg IV per protocol |
| Arm A: RP2D ALT-803 + Nivolumab (Nivo-naïve) | EXPERIMENTAL | Participants receive ALT-803 20 µg/kg + Nivolumab 3 mg/kg IV; Nivolumab-naïve population |
| Arm B: RP2D ALT-803 + Nivolumab (Nivo-progressor) | EXPERIMENTAL | Participants receive ALT-803 20 µg/kg + Nivolumab 3 mg/kg IV; prior Nivolumab exposure |
| Exploratory Arm 1 | NO_INTERVENTION | ALT-803 ± Nivolumab for biomarker analysis only |
| Exploratory Arm 2 | NO_INTERVENTION | ALT-803 ± Nivolumab for biomarker analysis only |
| Treatment | EXPERIMENTAL | Participants will start combined treatment with EV/Pembrolizumab (P) and NAI. Treatment will consist of up to 12 cycles of EV and up to 35 cycles of NAI and pembrolizumab (2 years). |
| Cohort 1: Dose level 0 Starting dose: N-803 + SIP-T | EXPERIMENTAL | Patients will receive standard dose (\>50 million CD54+ cells) subcutaneous (SC) SIP-T on Day 1, 15 and 29 and 15 mcg/kg SC dose of N-803 24 hours after SIP-T on Day 2, 16, and 30. |
| Cohort 1: Dose level -1: N-803 + SIP-T | EXPERIMENTAL | Patients will receive standard dose (\>50 million CD54+ cells) subcutaneous (SC) SIP-T on Day 1, 15 and 29 and 10 mcg/kg SC dose of N-803 24 hours after SIP-T on Day 2, 16, and 30. |
| Cohort 1: Dose level -2: N-803 + SIP-T | EXPERIMENTAL | Patients will receive standard dose (\>50 million CD54+ cells) subcutaneous (SC) SIP-T on Day 1, 15 and 29 and 6 mcg/kg SC dose of N-803 24 hours after SIP-T on Day 2, 16, and 30. |
| Cohort 2: N-803 + SIP-T | EXPERIMENTAL | Patients will receive standard dose (\>50 million CD54+ cells) subcutaneous (SC) SIP-T on Day 1, 15 and 29 and recommended phase 2 dose (RP2D) of N-803 24 hours after SIP-T on Day 2, 16, and 30. An additional dose of N-803 will occur on Day -5 or 5 days before first SIP-T dose. |
| Cohort 3: N-803 + SIP-T | EXPERIMENTAL | Patients will receive standard dose (\>50 million CD54+ cells) subcutaneous (SC) SIP-T on Day 1, 15 and 29 and RP2D of N-803 24 hours after SIP-T on Day 2, 16, and 30. An additional dose of N-803 will occur on Day 37. |
| Phase Ib Dose Level 1: Ipilimumab plus Nivolumab and Nogapendekin alfa inbakicept (N-803) | EXPERIMENTAL | Consenting and eligible patients will receive nivolumab intravenously (IV) on Days 1 and 22, ipilimumab IV on Day 1, and the assigned dose of nogapendekin alfa inbakicept subcutaneously (SC) on Days 1 and 22 of each cycle for Cycles 1 through 4; ipilimumab will be discontinued after Cycle 4 and patients will continue to receive nivolumab and nogapendekin alfa inbakicept on the same schedule for up to 2 years. Cycles are 42 days (6 weeks). |
| Phase Ib Dose Level -1: Ipilimumab plus Nivolumab and Nogapendekin alfa inbakicept (N-803) | EXPERIMENTAL | Consenting and eligible patients will receive nivolumab intravenously (IV) on Days 1 and 22, ipilimumab IV on Day 1, and the assigned dose of nogapendekin alfa inbakicept subcutaneously (SC) on Days 1 and 22 of each cycle for Cycles 1 through 4; ipilimumab will be discontinued after Cycle 4 and patients will continue to receive nivolumab and nogapendekin alfa inbakicept on the same schedule for up to 2 years. Cycles are 42 days (6 weeks). |
| Phase II: Ipilimumab plus Nivolumab and Nogapendekin alfa inbakicept (N-803) | EXPERIMENTAL | Consenting and eligible patients will receive nivolumab intravenously (IV) on Days 1 and 22, ipilimumab IV on Day 1, and the assigned dose of nogapendekin alfa inbakicept subcutaneously (SC) on Days 1 and 22 of each cycle for Cycles 1 through 4; ipilimumab will be discontinued after Cycle 4 and patients will continue to receive nivolumab and nogapendekin alfa inbakicept on the same schedule for up to 2 years. Cycles are 42 days (6 weeks). |
| Phase Ib/II ALT-803 w/ gemcitabine and nab-paclitaxel | EXPERIMENTAL | - |
| N-803+BCG | EXPERIMENTAL | (Phase Ib and IIb) for BCG-naive patients |
| BCG alone | ACTIVE_COMPARATOR | (Phase IIb) for BCG-naive patients |
| N-803 IV 0.3/0.5 ug/kg | EXPERIMENTAL | - |
| N-803 IV 1.0 ug/kg | EXPERIMENTAL | - |
| N-803 IV 3.0 ug/kg | EXPERIMENTAL | - |
| N-803 IV 6.0 ug/kg | EXPERIMENTAL | - |
| N-803 Subcutaneous 6.0 ug/kg | EXPERIMENTAL | - |
| N-803 Subcutaneous 10.0 ug/kg | EXPERIMENTAL | - |
| N-803 Subcutaneous 15.0 ug/kg | EXPERIMENTAL | - |
| N-803 Subcutaneous 20.0 ug/kg | EXPERIMENTAL | - |
| N-803 Intratumoral 10.0 ug/kg followed by N-803 15.0 ug/kg subcutaneous | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| N-803 | DRUG | N-803 1.2 mg SC |
| Tislelizumab | DRUG | Tislelizumab 200 mg IV |
| Docetaxel | DRUG | Docetaxel 75 mg/m2 IV |
| Prior failed checkpoint inhibitor | DRUG | Previously failed checkpoint inhibitor |
| Nogapendekin alfa inbakicept (NAI) | DRUG | Subcutaneous administration of nogapendekin alfa inbakicept (NAI; N-803, ANKTIVA®), a recombinant human IL-15 receptor agonist complex (IL-15N72D:IL-15RαSu/IgG1 Fc), at a fixed dose of 1.2 mg (0.6 mL at 2 mg/mL) on Day 1 (within 72 hours of sepsis recognition), with additional 1.2 mg doses on Day 14 if still hospitalized and on Day 21 if still hospitalized with ALC ≤ 1,000 cells/µL, given in combination with protocolized Surviving Sepsis Campaign-based standard of care. |
| Placebo | DRUG | Matching placebo administered subcutaneously according to the same dosing schedule and under the same conditions as nogapendekin alfa inbakicept (NAI), in combination with standard of care. The placebo is designed to maintain blinding and contains no active NAI. |
| hAd5-HPV Vaccine (IBRX-042) | BIOLOGICAL | IBRX-042 administered subcutaneously as part of the experimental treatment regimen. |
| Nab-Paclitaxel | DRUG | Nab-paclitaxel 100 mg/m² administered intravenously during neoadjuvant treatment cycles. |
| Cisplatin | DRUG | Cisplatin 40 mg/m² administered intravenously concurrently with radiation therapy. |
| De-Intensified IMRT | RADIATION | IMRT 40 Gy, delivered once daily, 5 days/week, over 4 weeks (20 total fractions) |
| Standard of Care IMRT | RADIATION | SOC IMRT 70 Gy, delivered once daily, 5 days/week, over 7 weeks (35 total fractions) |
| Standard of Care (SOC) | OTHER | Institutional standard of care for sepsis including antimicrobial therapy, fluid resuscitation, vasopressor support, organ support, and mechanical ventilation as clinically indicated |
| N-803 (IL-15 Superagonist) | DRUG | N-803 administered subcutaneously. |
| N-803 and BCG | DRUG | Combination therapy N-803 plus BCG |
| N-803 and Gemcitabine | DRUG | Combination therapy N-803 plus Gemcitabine |
| Anktiva | DRUG | 600ug of NAI administered subcutaneously |
| Gemcitabine | DRUG | Dose: 800 mg/m2 intravenously (IV) Frequency: administered on Day 1, Day 8, and Day 15 of each cycle (every 4 weeks) |
| M-CENK | BIOLOGICAL | Dose: 0.15 to 0.75 × 109 cells per infusion intravenously (IV) Frequency: administered on Day 1 of each cycle as long as M-CENK cells are available. |
| Aldoxorubicin HCl | DRUG | Aldoxorubicin hydrochloride |
| PD-L1 t-haNK | BIOLOGICAL | PD-L1 t-haNK suspension for infusion |
| Cyclophosphamide | DRUG | 2-\[bis(2-chloroethyl)amino\]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate |
| 5-Fluorouracil | DRUG | 5-fluoro-2,4 (1H,3H)-pyrimidinedione |
| Leucovorin | DRUG | L-Glutamic acid, N-\[4-\[\[(2-amino-5-formyl-1,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)methyl\]amino\]benzoyl\]-, calcium salt |
| SBRT | PROCEDURE | Stereotactic Body Radiation Therapy |
| Irinotecan liposome | DRUG | Irinotecan hydrochloride trihydrate is (S)-4,11-diethyl-3,4,12,14-tetrahydro-4-hydroxy-3,14-dioxo1H-pyrano\[3',4':6,7\]-indolizino\[1,2-b\]quinolin-9-yl-\[1,4'bipiperidine\]-1'-carboxylate, monohydrochloride, trihydrate |
| N-803 + Pembrolizumab | DRUG | Patients will receive 200 mg pembrolizumab as an intravenous infusion over 30 minutes every three weeks. Patients will receive 15 µg/kg N-803 administered by subcutaneous injection every three weeks. |
| N-803 + Nivolumab | DRUG | Patients will receive 240 mg nivolumab as an intravenous infusion over 30 minutes every two weeks. Patients will receive 15 µg/kg N-803 administered by subcutaneous injection every three weeks. |
| N-803 + Atezolizumab | DRUG | Patients will receive 1200 mg atezolizumab as an intravenous infusion over 60 minutes every 3 weeks; if the first infusion is tolerated, subsequent infusions may be given over 30 minutes. Patients will receive 15 µg/kg N-803 administered by subcutaneous injection every three weeks. |
| N-803 + Avelumab | DRUG | Patients will receive 800 mg avelumab as an intravenous infusion over 60 minutes every 2 weeks. Patients will receive 15 µg/kg N-803 administered by subcutaneous injection every three weeks. |
| N-803 + Durvalumab | DRUG | Patients will receive 10 mg/kg durvalumab as an intravenous infusion over 60 minutes every 2 weeks. Patients will receive 15 µg/kg N-803 administered by subcutaneous injection every three weeks. |
| N-803 + Pembrolizumab + PD-L1 t-haNK | DRUG | Patients will receive 200 mg pembrolizumab as an intravenous infusion over 30 minutes every three weeks. Patients will receive 15 µg/kg N-803 administered by subcutaneous injection every three weeks. Patients will receive PD-L1 t-haNK administered IV over 30 minutes at \~2 x 10\^9 cells/dose weekly |
| N-803 + Nivolumab + PD-L1 t-haNK | DRUG | Patients will receive 240 mg nivolumab as an intravenous infusion over 30 minutes every two weeks. Patients will receive 15 µg/kg N-803 administered by subcutaneous injection every three weeks. Patients will receive PD-L1 t-haNK administered IV over 30 minutes at \~2 x 10\^9 cells/dose weekly |
| N-803 + Atezolizumab + PD-L1 t-haNK | DRUG | Patients will receive 1200 mg atezolizumab as an intravenous infusion over 60 minutes every 3 weeks; if the first infusion is tolerated, subsequent infusions may be given over 30 minutes. Patients will receive 15 µg/kg N-803 administered by subcutaneous injection every three weeks. Patients will receive PD-L1 t-haNK administered IV over 30 minutes at \~2 x 10\^9 cells/dose weekly |
| N-803 + Avelumab + PD-L1 t-haNK | DRUG | Patients will receive 800 mg avelumab as an intravenous infusion over 60 minutes every 2 weeks. Patients will receive 15 µg/kg N-803 administered by subcutaneous injection every three weeks. Patients will receive PD-L1 t-haNK administered IV over 30 minutes at \~2 x 10\^9 cells/dose weekly |
| N-803 + Durvalumab + PD-L1 t-haNK | DRUG | Patients will receive 10 mg/kg durvalumab as an intravenous infusion over 60 minutes every 2 weeks. Patients will receive 15 µg/kg N-803 administered by subcutaneous injection every three weeks. Patients will receive PD-L1 t-haNK administered IV over 30 minutes at \~2 x 10\^9 cells/dose weekly |
| N-803 + Docetaxel + Pembrolizumab | DRUG | The study employs a 6-week cycle combination of: N-803 (1.2 mg flat dose SC), docetaxel (75 mg/m² IV - first 2 cycles only), and pembrolizumab (200 mg IV). |
| N-803 + Docetaxel + Nivolumab | DRUG | The study employs a 6-week cycle combination of:N-803 (1.2 mg flat dose SC), docetaxel (75 mg/m² IV - first 2 cycles only), and nivolumab (240 mg IV). Nivolumab dosing may be increased to 480mg every four weeks as per the investigator's discretion. |
| Graft cell infusion | PROCEDURE | -Day 0 |
| Tacrolimus | DRUG | -GVHD prophylaxis |
| Mycophenolate mofetil | DRUG | -GVHD prophylaxis |
| G-CSF | DRUG | -Continue until neutrophil engraftment as per institutional guidelines |
| CIML NK cell infusion | PROCEDURE | -Day +7 |
| ALT-803 | DRUG | -Start approximately 4 hours after CIML NK cell infusion |
| Leukapheresis | PROCEDURE | -Day +6 |
| N803 | DRUG | N-803 subcutaneously (SubQ) administered on day 1 of each 21-day cycle for up to 6 cycles. |
| Nivolumab | BIOLOGICAL | Nivolumab administered IV at 3 mg/kg per protocol |
| enfortumab vedotin (EV) | DRUG | 1.25 mg/kg given intravenously (IV) on Day 1 and Day 8 of each 3-week cycle, for approximately 5.5 to 8 months (8 to 12 cycles), but no more than 12 cycles. |
| Pembrolizumab | DRUG | 200 mg given intravenously (IV) every 3 weeks, for a maximum of 35 cycles (2 years) |
| Sipuleucel-T | BIOLOGICAL | Sipuleucel-T is a cellular therapeutic vaccine given in 3 complete doses at 2-week intervals intravenously. |
| Ipilimumab | DRUG | Ipilimumab will be given intravenously at a dose of 1mg/kg. |
| Nogapendekin alfa inbakicept | DRUG | Nogapendekin alfa inbakicept will be given subcutaneously at the assigned dose level. |
| CD19t-haNK suspension | BIOLOGICAL | Derived from the parental NK-92 (aNK) cell line, CD19 t-haNK is a human, allogeneic, NK cell line that has been engineered to express a CAR targeting CD19. Similar to the haNK cell line, CD19 t haNK has also been engineered to produce endoplasmic reticulum-retained IL 2 and the high-affinity (158V) variant of the Fcγ receptor (FcγRIIIa/CD16a), and thereby has enhanced CD16-targeted ADCC capabilities. CD19 t-haNK is similar to PD L1 t-haNK, differing only in the CAR that is expressed (CD19 vs PD-L1). |
| Fludarabine | DRUG | Fludarabine phosphate is a fluorinated nucleotide analog of the antiviral agent vidarabine, 9-β-D-arabinofuranosyladenine (ara-A) that is relatively resistant to deamination by adenosine deaminase. The chemical name for fludarabine phosphate is 9H-Purin-6-amine, 2-fluoro-9-(5-0-phosphono β-D-arabino-furanosyl) (2-fluoro-ara-AMP). The molecular formula of fludarabine phosphate is C10H13FN5O7P and it has a molecular weight of 365.2. |
| Rituximab | DRUG | Rituximab is a genetically engineered chimeric murine/human monoclonal IgG1 kappa antibody directed against the CD20 antigen. Rituximab has an approximate molecular weight of 145 kD and has a binding affinity for the CD20 antigen of approximately 8.0 nM. |
| BCG (50mg/instillation) + N-803 (400 μg/instillation) | BIOLOGICAL | BCG and N-803 will be mixed together (with saline) and administered via intravesical instillation weekly for 6 consecutive weeks for induction. Phase IIb includes maintenance treatment consisting of BCG+N-803 for 3 consecutive weeks at 3, 6, 12, 18, 24, 30 and 36 months. An additional 6-week re-induction of BCG+N-803 for patients with eligible disease at 3 months in phase IIb is included. |
| BCG (50mg/instillation) | BIOLOGICAL | BCG will be administered via intravesical instillation weekly for 6 consecutive weeks for induction. Phase IIb includes maintenance treatment consisting of BCG for 3 consecutive weeks at 3, 6, 12, 18, 24, 30 and 36 months. An additional 6-week re-induction of BCG for patients with eligible disease at 3 months in phase IIb is included. |
Eligibility Criteria: Women and men of all races and ethnic groups are eligible for this trial. Cohort A Inclusion Criteria: 1. Age ≥ 18 years old. 2. Able to understand and provide a signed informed consent that fulfills the relevant Institutional Review Board (IRB) or Independent Ethics Commit...
Nogapendekin alfa inbakicept is an investigational oncology therapy developed by ImmunityBio, Inc. (ticker IBRX). It is being studied across several cancer types, including bladder cancer, acute myeloid leukemia, advanced pancreatic cancer, advanced solid tumors, B-cell non Hodgkin lymphoma, and HPV-positive oropharyngeal squamous cell carcinoma. It is also known by the names N-803, ALT-803, and Anktiva.
Nogapendekin alfa inbakicept targets IL2RG, IL2RB, and IL15RA, acting as an agonist at these receptors. By binding these interleukin receptor subunits, it is designed to stimulate immune signaling. This target profile places it among immune agonist agents being evaluated in oncology settings.
ImmunityBio, Inc., which trades under the ticker IBRX, is the developer of nogapendekin alfa inbakicept. The company is running the clinical program for the asset across multiple cancer indications and, in some studies, in sepsis-related conditions.
Nogapendekin alfa inbakicept is in Phase 2 development. It is an investigational agent and is not described as approved. The program includes Phase 1 and Phase 2 trials, with a total of 507 participants enrolled across the studies and two trials currently active.
Trials include NCT07783789, a Phase 2 study of NAI plus standard of care versus placebo plus standard of care in critically ill adults with sepsis, and NCT07756593, a Phase 1 study of sipuleucel-T combined with N-803 in metastatic androgen pathway modulation resistant prostate cancer. NCT07628062 and NCT07578558 are additional Phase 2 studies.
Yes, nogapendekin alfa inbakicept is also known as N-803, ALT-803, N803, NAI, and Anktiva, among other names. These refer to the same investigational agent developed by ImmunityBio, Inc. (IBRX), so search results using any of these names describe the same drug program.