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    DRUG CLASS:

    CD122 agonist

    Related drugs:
    12d
    Type 2 responses determine skin rash during recombinant interleukin-2 therapy. (PubMed, J Immunotoxicol)
    One of the drugs inducing CADRs is aldesleukin, a recombinant interleukin-2 (recIL-2) originally approved to treat malignant melanoma and metastatic renal cell carcinoma which frequently led to skin rashes when applied in high doses for anti-cancer therapy...Together, this hypothetic irAOP forms a basis to clarify possible cellular and molecular interactions leading to recIL-2-induced skin rash. This might be used to adapt existing or develop new test systems to help predict and prevent cutaneous side effects in future IL-2-based or similar therapies.
    Review • Journal
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    IL2 (Interleukin 2)
    |
    Proleukin (aldesleukin)
    18d
    BelieveIT-201: TransCon (TC) TLR7/8 Agonist, TC IL-2 β/γ, Pembrolizumab Prior to Surgery for Advanced Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov)
    P2, N=27, Active, not recruiting, Ascendis Pharma A/S | Recruiting --> Active, not recruiting | N=92 --> 27
    Enrollment closed • Enrollment change • Combination therapy • Surgery • Metastases
    |
    Keytruda (pembrolizumab) • onvapegleukin alfa (TransCon IL-2 β/γ) • resiquimod SR (TransCon TLR7/8 Agonist)
    27d
    A Study to Evaluate the Safety and Therapeutic Activity of GI-102 As a Single Agent and in Combination with Conventional Anti-cancer Drugs, Pembrolizumab or Trastuzumab Deruxtecan(T-DXd) in Patients with Advanced Solid Tumors (KEYNOTE-G08) (clinicaltrials.gov)
    P1/2, N=358, Recruiting, GI Innovation, Inc. | N=92 --> 358 | Trial completion date: Jun 2025 --> Apr 2027 | Trial primary completion date: Apr 2025 --> Nov 2025
    Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • Metastases
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    CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
    |
    Keytruda (pembrolizumab) • Avastin (bevacizumab) • paclitaxel • Enhertu (fam-trastuzumab deruxtecan-nxki) • doxorubicin hydrochloride • Halaven (eribulin mesylate)
    1m
    TIL Therapy for Metastatic Renal Cell Carcinoma (clinicaltrials.gov)
    P1, N=5, Completed, Inge Marie Svane | Unknown status --> Completed
    Trial completion • Metastases
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    IL2 (Interleukin 2)
    |
    cyclophosphamide • fludarabine IV • Proleukin (aldesleukin)
    1m
    Gene and Vaccine Therapy in Treating Patients With Advanced Malignancies (clinicaltrials.gov)
    P2, N=6, Active, not recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Nov 2025 --> Nov 2026 | Trial primary completion date: Nov 2024 --> Nov 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    CTAG1B (Cancer/testis antigen 1B)
    |
    cyclophosphamide • fludarabine IV • Proleukin (aldesleukin)
    2ms
    Bempegaldesleukin plus nivolumab in first-line advanced/metastatic urothelial carcinoma: Results from a phase II single-arm study (PIVOT-10). (PubMed, Urol Oncol)
    BEMPEG plus NIVO did not meet the efficacy threshold for ORR in patients with previously untreated locally advanced or metastatic urothelial carcinoma and low PD-L1 expression.
    P2 data • Journal • PD(L)-1 Biomarker • IO biomarker • Metastases
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    PD-L1 (Programmed death ligand 1) • IL2 (Interleukin 2)
    |
    PD-L1 expression • PD-L1 underexpression • PD-L1-L
    |
    Opdivo (nivolumab) • bempegaldesleukin (NKTR-214)
    2ms
    Adoptive Cell Therapy Across Cancer Diagnoses (clinicaltrials.gov)
    P1/2, N=25, Completed, Inge Marie Svane | Unknown status --> Completed
    Trial completion
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    IL2 (Interleukin 2)
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • cyclophosphamide • fludarabine IV • Proleukin (aldesleukin)
    2ms
    An Open-Label Dose-Escalation Study to Evaluate XmAb24306 as a Single Agent and in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1, N=250, Active, not recruiting, Genentech, Inc. | Recruiting --> Active, not recruiting
    Enrollment closed • Combination therapy • Metastases
    |
    Tecentriq (atezolizumab)
    2ms
    Genetically Modified T-Cells Followed by Aldesleukin in Treating Patients with Stage III-IV Melanoma (clinicaltrials.gov)
    P1, N=34, Active, not recruiting, M.D. Anderson Cancer Center | N=15 --> 34 | Trial completion date: Jun 2025 --> Oct 2027 | Trial primary completion date: Jun 2024 --> Oct 2027
    Enrollment change • Trial completion date • Trial primary completion date • Metastases
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    NGFR (Nerve Growth Factor Receptor) • TGFA (Transforming Growth Factor Alpha)
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    cyclophosphamide • fludarabine IV • Proleukin (aldesleukin)
    3ms
    STIL101 for Injection for the Treatment of Locally Advanced, Metastatic or Unresectable Pancreatic Cancer, Colorectal Cancer, Renal Cell Cancer, Cervical Cancer and Melanoma (clinicaltrials.gov)
    P1, N=12, Not yet recruiting, City of Hope Medical Center
    New P1 trial
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    cyclophosphamide • fludarabine IV • Proleukin (aldesleukin)
    4ms
    Entinostat in Combination With Aldesleukin in Treating Patients With Metastatic Kidney Cancer (clinicaltrials.gov)
    P1/2, N=47, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2024 --> Jul 2025
    Trial completion date • Combination therapy • Epigenetic controller • Metastases
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    mTOR (Mechanistic target of rapamycin kinase)
    |
    Jingzhuda (entinostat) • Proleukin (aldesleukin)
    5ms
    Baseline biomarkers of efficacy and on-treatment immune-profile changes associated with bempegaldesleukin plus nivolumab. (PubMed, NPJ Precis Oncol)
    Changes in tumor biomarkers were comparable between arms. These biomarker results help provide a better understanding of the mechanism of action of BEMPEG + NIVO and may help contextualize the clinical observations from PIVOT IO 001.
    Journal • Tumor mutational burden • PD(L)-1 Biomarker
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    TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • CD4 (CD4 Molecule) • IL2 (Interleukin 2)
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    Opdivo (nivolumab) • bempegaldesleukin (NKTR-214)
    5ms
    A Study to Evaluate the Safety and Pharmacokinetics of XMAB24306 in Combination With Daratumumab in Participants With Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov)
    P1, N=18, Completed, Genentech, Inc. | Recruiting --> Completed | N=60 --> 18 | Trial completion date: Jul 2026 --> Jun 2024 | Trial primary completion date: Jan 2026 --> Jun 2024
    Trial completion • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy
    |
    Darzalex Faspro (daratumumab and hyaluronidase-fihj)
    6ms
    Study of LTC004 Combine With Toripalimab in Patient With Solid Tumors Resistant to Immunotherapy (clinicaltrials.gov)
    P2, N=10, Recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
    New P2 trial • Combination therapy • Metastases
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    Loqtorzi (toripalimab-tpzi) • LTC004
    6ms
    PIVOT IO 001: A Study of NKTR-214 Combined With Nivolumab vs Nivolumab Alone in Participants With Previously Untreated Inoperable or Metastatic Melanoma (clinicaltrials.gov)
    P3, N=783, Completed, Bristol-Myers Squibb | Trial completion date: Sep 2023 --> Mar 2024
    Trial completion date • Metastases
    |
    Opdivo (nivolumab) • bempegaldesleukin (NKTR-214)
    7ms
    Bempegaldesleukin Plus Nivolumab Versus Sunitinib or Cabozantinib in Previously Untreated Advanced Clear Cell Renal Cell Carcinoma: A Phase III Randomized Study (PIVOT-09). (PubMed, J Clin Oncol)
    First-line BEMPEG plus NIVO for advanced/metastatic ccRCC did not improve efficacy in patients with intermediate-/poor-risk disease but led to fewer grade 3/4 TRAEs versus TKI.
    P3 data • Journal • Metastases
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    IL2 (Interleukin 2)
    |
    Opdivo (nivolumab) • sunitinib • Cabometyx (cabozantinib tablet) • bempegaldesleukin (NKTR-214)
    7ms
    Phase I/II Study of Autologous T Cells to Express T-Cell Receptors (TCRs) in Subjects With Solid Tumors (clinicaltrials.gov)
    P1/2, N=180, Active, not recruiting, Alaunos Therapeutics | Trial completion date: Mar 2029 --> Nov 2024 | Trial primary completion date: Dec 2025 --> Nov 2024
    Trial completion date • Trial primary completion date • IO biomarker
    |
    IFNG (Interferon, gamma) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • IL2 (Interleukin 2)
    |
    Proleukin (aldesleukin)
    7ms
    An Open-Label Dose-Escalation Study to Evaluate XmAb24306 as a Single Agent and in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1, N=250, Recruiting, Genentech, Inc. | Trial completion date: Jun 2024 --> Sep 2025 | Trial primary completion date: Jun 2024 --> Sep 2025
    Trial completion date • Trial primary completion date
    |
    Tecentriq (atezolizumab)
    7ms
    IL-15/IL-15Rα-Fc fusion protein XmAb24306 potentiates activity of CD3 bispecific antibodies through enhancing T cell expansion. (PubMed, Mol Cancer Ther)
    Activation of human peripheral T cells by cevostamab, an anti-FcRH5/CD3 TDB, or anti-HER2/CD3 TDB resulted in upregulation of IL-2/15Rβ (CD122) receptor subunit in nearly all CD8+ and majority of CD4+ T cells, suggesting that TDB treatment may sensitize T cells to the IL-15. In summary, our results support the hypothesis where the number of tumor infiltrating T cells is rate limiting for the activity of solid tumor targeting TDBs. Upregulation of CD122 by TDB treatment and the observed synergy with XmAb24306 and T cell bispecific antibodies supports clinical evaluation of this novel immunotherapy combination.
    Journal
    |
    CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • IL2 (Interleukin 2) • IL15 (Interleukin 15)
    |
    cevostamab (RG6160)
    7ms
    Aerosolized Aldesleukin in Treating Patients With Lung Metastases (clinicaltrials.gov)
    P1, N=70, Active, not recruiting, M.D. Anderson Cancer Center | Phase classification: P1/2 --> P1 | Trial completion date: Apr 2024 --> Apr 2026 | Trial primary completion date: Apr 2024 --> Apr 2026
    Phase classification • Trial completion date • Trial primary completion date
    |
    Proleukin (aldesleukin)
    8ms
    A Study of NKTR-214 in Combination With Nivolumab in Patients With Metastatic and/or Locally Advanced Sarcoma (clinicaltrials.gov)
    P2, N=88, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    Opdivo (nivolumab) • bempegaldesleukin (NKTR-214)
    8ms
    Isotretinoin With or Without Dinutuximab, Aldesleukin, and Sargramostim Following Stem Cell Transplant in Treating Patients With Neuroblastoma (clinicaltrials.gov)
    P3, N=1449, Active, not recruiting, National Cancer Institute (NCI)
    Trial completion date
    |
    MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • NCR3LG1 (Natural Killer Cell Cytotoxicity Receptor 3 Ligand 1)
    |
    Proleukin (aldesleukin) • Qarziba (dinutuximab beta) • Unituxin (dinutuximab) • Leukine (sargramostim)
    8ms
    Genetically Modified T-Cells Followed by Aldesleukin in Treating Patients With Stage III-IV Melanoma (clinicaltrials.gov)
    P1, N=15, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting
    Enrollment closed • Metastases
    |
    NGFR (Nerve Growth Factor Receptor) • TGFA (Transforming Growth Factor Alpha)
    |
    cyclophosphamide • fludarabine IV • Proleukin (aldesleukin)
    8ms
    CD8+ Antigen-Specific T Cells, Cyclophosphamide, Aldesleukin, and Ipilimumab in Treating Patients With Metastatic Melanoma (clinicaltrials.gov)
    P2, N=16, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Jan 2025 --> Apr 2024 | Trial primary completion date: Jan 2025 --> Apr 2024
    Trial completion • Trial completion date • Trial primary completion date • Metastases
    |
    BRAF (B-raf proto-oncogene) • IL2 (Interleukin 2) • MLANA (Melan-A)
    |
    BRAF mutation • BRAF V600
    |
    Yervoy (ipilimumab) • cyclophosphamide • Proleukin (aldesleukin)
    9ms
    Efbalropendekin Alfa enhances human natural killer cell cytotoxicity against tumor cell lines in vitro. (PubMed, Front Immunol)
    Daratumumab (dara), a monoclonal antibody (mAb) that targets CD38 results in antibody-dependent cellular cytotoxicity (ADCC) of both multiple myeloma (MM) cells and NK cells. Because NK cells express CD38, XmAb24306 increases dara-mediated NK cell fratricide, but overall does not negatively impact the ADCC activity against a MM cell line likely due to increased NK cell activity of the surviving cells. These data show that XmAb24306 increases direct and ADCC-mediated human NK cell cytotoxicity in vitro.
    Preclinical • Journal • IO biomarker • Tumor cell
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    IL15 (Interleukin 15)
    |
    CD38 expression
    |
    Darzalex (daratumumab)
    9ms
    Non-Viral TCR Gene Therapy (clinicaltrials.gov)
    P2, N=0, Withdrawn, National Cancer Institute (NCI) | N=210 --> 0 | Trial completion date: Dec 2029 --> Mar 2024 | Not yet recruiting --> Withdrawn | Trial primary completion date: Dec 2028 --> Mar 2024
    Enrollment change • Trial completion date • Trial withdrawal • Trial primary completion date • IO biomarker • Gene therapy • Metastases
    |
    cyclophosphamide • fludarabine IV • Proleukin (aldesleukin)
    10ms
    A Placebo Controlled Trial of Bempegaldesleukin (BEMPEG; NKTR-214) With Standard of Care in Patients With Mild COVID-19 (clinicaltrials.gov)
    P1, N=30, Completed, Nektar Therapeutics | Phase classification: P1b --> P1
    Phase classification
    |
    bempegaldesleukin (NKTR-214)
    10ms
    PIVOT IO 011: A Study to Compare Bempegaldesleukin (BEMPEG: NKTR-214) Combined With Nivolumab and Tyrosine Kinase Inhibitor (TKI) to Nivolumab and TKI Alone in Participants With Previously Untreated Kidney Cancer That is Advanced or Has Spread (clinicaltrials.gov)
    P1, N=30, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed
    Trial completion
    |
    PD-L1 (Programmed death ligand 1)
    |
    Opdivo (nivolumab) • Cabometyx (cabozantinib tablet) • Inlyta (axitinib) • bempegaldesleukin (NKTR-214)
    10ms
    Autologous T-cells Genetically Engineered to Express Receptors Reactive Against KRAS Mutations in Conjunction With a Vaccine Directed Against These Antigens in Participants With Metastatic Cancer (clinicaltrials.gov)
    P1, N=210, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting
    Enrollment open
    |
    cyclophosphamide • fludarabine IV • Proleukin (aldesleukin) • SLATE-KRAS
    10ms
    ABILITY: A Beta-only IL-2 ImmunoTherapY Study (clinicaltrials.gov)
    P1/2, N=115, Recruiting, Medicenna Therapeutics, Inc. | Trial primary completion date: Sep 2024 --> Jun 2026
    Trial primary completion date • Combination therapy • Checkpoint inhibition • Metastases
    |
    Keytruda (pembrolizumab) • MDNA11
    10ms
    Autologous T-cells Genetically Engineered to Express Receptors Reactive Against KRAS Mutations in Conjunction With a Vaccine Directed Against These Antigens in Participants With Metastatic Cancer (clinicaltrials.gov)
    P1, N=210, Not yet recruiting, National Cancer Institute (NCI)
    New P1 trial
    |
    cyclophosphamide • fludarabine IV • Proleukin (aldesleukin) • SLATE-KRAS
    10ms
    Selective targeting or reprogramming of intra-tumoral Tregs. (PubMed, Med Oncol)
    Anti-CCR8 and the IL-2Rβγ agonist Bempegaldesleukin selectively target intra-tumoral Treg population, with the former approved to not elicit autoimmunity...Blimp-1 inhibitors and glucocorticoid-induced TNFR-related protein agonists are example approaches that can be used for diverting Treg differentiation into Th1-like CD4+ T cells, thereby powering immunogenicity against cancer. Finally, selective target of intra-tumoral Tregs and their reprogramming into effector T cells is applicable using low-dose chemotherapy, and high-salt and high-tryptophan diet.
    Review • Journal
    |
    CD4 (CD4 Molecule) • PRDM1 (PR/SET Domain 1) • CCR8 (C-C Motif Chemokine Receptor 8) • TRPS1 (Transcriptional Repressor GATA Binding 1)
    |
    bempegaldesleukin (NKTR-214)
    11ms
    Immunotherapy for the Treatment of Advanced Solid Tumor (clinicaltrials.gov)
    P1/2, N=40, Recruiting, Tongji Hospital | Not yet recruiting --> Recruiting
    Enrollment open
    |
    cyclophosphamide • fludarabine IV • Proleukin (aldesleukin)
    11ms
    Study of High Dose Interleukin-2 (IL-2) and Stereotactic Body Radiation (SBRT) in Patients With Metastatic Renal Cancer (clinicaltrials.gov)
    P2, N=84, Active, not recruiting, Providence Health & Services | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2023 --> Dec 2024
    Trial completion date • Trial primary completion date • Metastases
    |
    IL2 (Interleukin 2)
    |
    Proleukin (aldesleukin)
    12ms
    Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12V Variant of Mutated RAS in HLA-A*11:01 Patients (clinicaltrials.gov)
    P1/2, N=8, Suspended, National Cancer Institute (NCI) | N=110 --> 8 | Recruiting --> Suspended
    Enrollment change • Trial suspension • IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog)
    |
    KRAS mutation • NRAS mutation • KRAS G12V • HRAS mutation • KRAS G12 • NRAS G12 • HLA-A*11 • NRAS G12V
    |
    cyclophosphamide • fludarabine IV • Proleukin (aldesleukin)
    12ms
    Lymphodepletion Plus Adoptive Cell Transfer With High Dose IL-2 in Patients With Metastatic Melanoma (clinicaltrials.gov)
    P=N/A, N=19, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Dec 2023 --> Dec 2024
    Trial completion date • Metastases
    |
    IFNG (Interferon, gamma)
    |
    cyclophosphamide • Proleukin (aldesleukin)
    12ms
    T-Cell Infusion, Aldesleukin, and Utomilumab in Treating Patients With Recurrent Ovarian Cancer (clinicaltrials.gov)
    P1/2, N=8, Completed, M.D. Anderson Cancer Center | Suspended --> Completed
    Trial completion • Combination therapy
    |
    HLA-A (Major Histocompatibility Complex, Class I, A) • PRAME (Preferentially Expressed Antigen In Melanoma) • COL6A3 (Collagen Type VI Alpha 3 Chain)
    |
    PRAME expression
    |
    cyclophosphamide • Proleukin (aldesleukin) • utomilumab (PF-05082566)
    1year
    Gene and Vaccine Therapy in Treating Patients With Advanced Malignancies (clinicaltrials.gov)
    P2, N=6, Active, not recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2023 --> Nov 2024
    Trial completion date • Trial primary completion date
    |
    CTAG1B (Cancer/testis antigen 1B)
    |
    cyclophosphamide • fludarabine IV • Proleukin (aldesleukin)
    1year
    CD8+ Antigen-Specific T Cells, Cyclophosphamide, Aldesleukin, and Ipilimumab in Treating Patients With Metastatic Melanoma (clinicaltrials.gov)
    P2, N=16, Active, not recruiting, M.D. Anderson Cancer Center | N=30 --> 16 | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025
    Enrollment change • Trial completion date • Trial primary completion date • Metastases
    |
    BRAF (B-raf proto-oncogene) • IL2 (Interleukin 2) • MLANA (Melan-A)
    |
    BRAF mutation • BRAF V600
    |
    Yervoy (ipilimumab) • cyclophosphamide • Proleukin (aldesleukin)
    1year
    Aldesleukin With Nivolumab and Standard Chemotherapy for Treatment of Gastric Cancer With Peritoneal Metastasis (clinicaltrials.gov)
    P1, N=15, Recruiting, Mayo Clinic | Not yet recruiting --> Recruiting
    Enrollment open
    |
    Opdivo (nivolumab) • oxaliplatin • leucovorin calcium • Proleukin (aldesleukin) • fluorouracil topical
    1year
    Aldesleukin With Nivolumab and Standard Chemotherapy for Treatment of Gastric Cancer With Peritoneal Metastasis (clinicaltrials.gov)
    P1, N=15, Not yet recruiting, Mayo Clinic | Phase classification: P1b --> P1
    Phase classification
    |
    Opdivo (nivolumab) • oxaliplatin • leucovorin calcium • Proleukin (aldesleukin) • fluorouracil topical
    1year
    An Open-Label Dose-Escalation Study to Evaluate XmAb24306 as a Single Agent and in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1, N=250, Recruiting, Genentech, Inc. | Phase classification: P1a/1b --> P1
    Phase classification • Combination therapy • Metastases
    |
    Tecentriq (atezolizumab)