resiquimod pegol (NKTR-262) / Nektar Therap - LARVOL DELTA

Combining Bempegaldesleukin (CD122-preferential IL-2 pathway agonist) and NKTR-262 (TLR7/8 agonist) pairs local innate activation with systemic CD8+ T cell expansion to enhance anti-tumor immunity (SITC 2021) - P1/2 | "Enhancement of the activated CD8+ T cell response in mice treated with NKTR-262 in combination with BEMPEG suggests that intratumoral TLR stimulation provides superior antigen presentation and costimulatory activity compared to RT. A clinical trial of BEMPEG/NKTR-262 for patients with metastatic solid tumors is in progress (NCT03435640)."

IO biomarker • Oncology • Solid Tumor • CD4 • CD8 • GZMA • HAVCR2 • ICOS • IL2 • PD-1

[VIRTUAL] Combining Bempegaldesleukin (CD122-preferential IL-2 pathway agonist) and NKTR-262 (TLR7/8 agonist) pairs local innate activation with systemic CD8+ T cell expansion to enhance anti-tumor immunity (SITC 2020) - P1/2 | "The improved tumor regression and survival was dependent on the NKTR-262 driven expansion of NK cells. A clinical trial of BEMPEG/NKTR-262 for patients with metastatic solid tumors is in progress (NCT03435640)."

IO Biomarker • Oncology • Solid Tumor • CD8 • GZMA • HAVCR2 • ICOS • IL2 • PD-1

[VIRTUAL] Combining Bempegaldesleukin (CD122-preferential IL-2 pathway agonist) and NKTR-262 (TLR7/8 agonist) pairs local innate activation with systemic CD8+ T cell expansion to enhance anti-tumor immunity (SITC 2020) - P1/2 | "The improved tumor regression and survival was dependent on the NKTR-262 driven expansion of NK cells. A clinical trial of BEMPEG/NKTR-262 for patients with metastatic solid tumors is in progress (NCT03435640)."

IO Biomarker • Oncology • Solid Tumor • CD8 • GZMA • HAVCR2 • ICOS • IL2 • PD-1

[VIRTUAL] REVEAL: Phase 1 dose-escalation study of NKTR-262, a novel TLR7/8 agonist, plus bempegaldesleukin: local innate immune activation and systemic adaptive immune expansion for treating solid tumors (SITC 2020) - P1/2 | "Trial Registration NCT03435640. Robust TLR7/8 engagement supported the NKTR-262 mechanism of action, while the minimal toxicity profile underscored the benefit of local delivery of NKTR-262, and the BEMPEG combination induced systemic activation of T and NK cells. These data support the RP2D of NKTR-262 (3.84 mg IT) plus BEMPEG (0.006 mg IV) q3w, and the initiation of the phase 1b dose-expansion phase, which is exploring concurrent dosing, with or without nivolumab, in relapsed/refractory metastatic melanoma patients."

P1 data • Melanoma • Oncology • Solid Tumor • CD8 • CXCL10 • IL2

REVEAL: A phase 1/2, open-label, multicenter, dose escalation and dose expansion study of NKTR-262 [TLR 7/8 agonist] plus NKTR-214 [CD122-biased agonist] with or without nivolumab (nivo) in patients (pts) with locally advanced or metastatic solid tumor malignancies (ESMO 2018) - P1/2; "Pts in the NKTR-262 + NKTR-214 cohorts will have progressed on prior approved therapies and pts in the NKTR-262 + NKTR-214 + nivo cohorts will be naïve to immunotherapy treatment. Trial is open and recruiting."

Clinical • P1/2 data • Bladder Cancer • Colorectal Cancer • Melanoma • Neuroendocrine Tumor • Ovarian Cancer • Renal Cell Carcinoma • Sarcoma • Triple Negative Breast Cancer

Phase Ib: Preliminary clinical activity and immune activation for NKTR-262 [TLR 7/8 agonist] plus NKTR-214 [CD122-biased agonist] in patients (pts) with locally advanced or metastatic solid tumors (REVEAL Phase Ib/II Trial). (ASCO-SITC 2019) - P1/2; "NKTR-262 + NKTR-214 engage the immune activation cascade from local tumor antigen production to anti-tumor T cell response. Initial dose levels of NKTR-262 with fixed-dose NKTR-214 were well-tolerated with early evidence of clinical activity. These data support continued evaluation of the combination +/- nivolumab."

Clinical • P1/2 data • PD(L)-1 Biomarker

REVEAL: A Study of NKTR-262 in Combination With Bempegaldesleukin (NKTR-214) and With Bempegaldesleukin Plus Nivolumab in Patients With Locally Advanced or Metastatic Solid Tumor Malignancies (clinicaltrials.gov) - P1/2 | N=64 | Terminated | Sponsor: Nektar Therapeutics | Trial completion date: Oct 2022 ➔ May 2022 | Active, not recruiting ➔ Terminated; Based on the overall results from the Phase 1 part of the study the sponsor decided to end the study. The decision was not due to safety reasons.

Combination therapy • Trial completion date • Trial termination • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Melanoma • Merkel Cell Carcinoma • Neuroendocrine Tumor • Non-melanoma Skin Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • PD-1 • PD-L1

Combining bempegaldesleukin (CD122-preferential IL-2 pathway agonist) and NKTR-262 (TLR7/8 agonist) improves systemic antitumor CD8 T cell cytotoxicity over BEMPEG+RT. (PubMed, J Immunother Cancer) - P1/2 | "BEMPEG+NKTR-262 therapy elicited more robust expansion of activated CD8 T cells compared with BEMPEG+RT, suggesting that intratumoral TLR stimulation provides superior antigen presentation and costimulatory activity compared with RT. A clinical trial of BEMPEG+NKTR-262 for patients with metastatic solid tumors is in progress (NCT03435640)."

IO biomarker • Journal • Immune Modulation • Immunology • Inflammation • Oncology • Solid Tumor • CD4 • CD8 • GZMA • ICOS • IL2 • PD-1

"Just out!!! @AnnahRolig @ChilesResearch @NektarNews highlights combo #immunotherapy. Combining bempegaldesleukin (CD122-preferential IL-2 pathway agonist) and NKTR-262 (TLR7/8 agonist) improves systemic antitumor CD8+ T cell cytotoxicity over BEMPEG+RT https://t.co/JSzTPFJdHv" (@WWredmond4)

Oncology • CD8 • IL2

Nektar Therapeutics Announces Data Presentations for Its Immuno-Oncology Pipeline at the 2021 Society for Immunotherapy of Cancer (SITC) Annual Meeting (PRNewswire) - "In preclinical models, BEMPEG+NKTR-262 therapy induces active (GzmA+, Ki-67+) AH1-A5-CD8+ T cell that are supported by type 1 IFN signaling, suggesting bystander T cell activity. In preclinical models, BEMPEG+NKTR-262 combination therapy induces intratumoral CD8+ T cells that have increased activity as demonstrated by increased granzyme expression, increased cytolytic capacity, and reduced conversion to an exhausted phenotype (PD-1+)."

Preclinical • Oncology

Nektar Therapeutics to Host Webcast Conference Call for Analysts & Investors with Cancer Specialist During 2021 Society for Immunotherapy of Cancer (SITC) 36th Annual Meeting (PRNewswire) - "Nektar Therapeutics...announced today that it will host a webcast analyst and investor conference call with a cancer specialist and Nektar management on Friday, November 12, 2021, at 12:00 p.m. EST during the 2021 Society for Immunotherapy of Cancer (SITC) Annual Meeting....The event will follow the publication of the NKTR-255 poster (Abstract #957) on Friday morning."

Clinical data • Breast Cancer • Colorectal Cancer • Genito-urinary Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

REVEAL: A Study of NKTR-262 in Combination With Bempegaldesleukin (NKTR-214) and With Bempegaldesleukin Plus Nivolumab in Patients With Locally Advanced or Metastatic Solid Tumor Malignancies (clinicaltrials.gov) - P1/2; N=64; Active, not recruiting; Sponsor: Nektar Therapeutics; Trial completion date: Dec 2021 ➔ Oct 2022; Trial primary completion date: Sep 2021 ➔ Jul 2022

Clinical • Combination therapy • Trial completion date • Trial primary completion date • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Melanoma • Merkel Cell Carcinoma • Neuroendocrine Tumor • Non-melanoma Skin Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • PD-1 • PD-L1

Phase Ib: Preliminary clinical activity and immune activation for NKTR-262 [TLR 7/8 agonist] plus NKTR-214 [CD122-biased agonist] in patients (pts) with locally advanced or metastatic solid tumors (REVEAL Phase Ib/II Trial). (ASCO-SITC 2019) - P1/2; "NKTR-262 + NKTR-214 engage the immune activation cascade from local tumor antigen production to anti-tumor T cell response. Initial dose levels of NKTR-262 with fixed-dose NKTR-214 were well-tolerated with early evidence of clinical activity. These data support continued evaluation of the combination +/- nivolumab."

Clinical • P1/2 data • PD(L)-1 Biomarker

[VIRTUAL] REVEAL: Phase 1 dose-escalation study of NKTR-262, a novel TLR7/8 agonist, plus bempegaldesleukin: local innate immune activation and systemic adaptive immune expansion for treating solid tumors (SITC 2020) - P1/2 | "Trial Registration NCT03435640. Robust TLR7/8 engagement supported the NKTR-262 mechanism of action, while the minimal toxicity profile underscored the benefit of local delivery of NKTR-262, and the BEMPEG combination induced systemic activation of T and NK cells. These data support the RP2D of NKTR-262 (3.84 mg IT) plus BEMPEG (0.006 mg IV) q3w, and the initiation of the phase 1b dose-expansion phase, which is exploring concurrent dosing, with or without nivolumab, in relapsed/refractory metastatic melanoma patients."

P1 data • Melanoma • Oncology • Solid Tumor • CD8 • CXCL10 • IL2

Phase Ib: Preliminary clinical activity and immune activation for NKTR-262 [TLR 7/8 agonist] plus NKTR-214 [CD122-biased agonist] in patients (pts) with locally advanced or metastatic solid tumors (REVEAL Phase Ib/II Trial). (ASCO-SITC 2019) - P1/2; "NKTR-262 + NKTR-214 engage the immune activation cascade from local tumor antigen production to anti-tumor T cell response. Initial dose levels of NKTR-262 with fixed-dose NKTR-214 were well-tolerated with early evidence of clinical activity. These data support continued evaluation of the combination +/- nivolumab."

Clinical • P1/2 data • PD(L)-1 Biomarker

Current status of intralesional agents in treatment of malignant melanoma. (PubMed, Ann Transl Med) - "This review focuses on the current status of IT agents currently under clinical trials in melanoma. Reviewed therapies include T-VEC, T-VEC with immune checkpoint inhibitors including ipilimumab and pembrolizumab or other agents, RP1, OrienX010, Canerpaturev (C-REV, HF10), CAVATAK (coxsackievirus A21, CVA21) alone or in combination with checkpoint inhibitors, oncolytic polio/rhinovirus recombinant (PVSRIPO), MAGE-A3-expressing MG1 Maraba virus, VSV-IFNbetaTYRP1, suicide gene therapy, ONCOS-102, OBP-301 (Telomelysin), Stimulation of Interferon Genes Pathway (STING agonists) including DMXAA, MIW815 (ADU-S100) and MK-1454, PV-10, toll-like receptors (TLRs) agonists including TLR-9 agonists (SD-101, CMP-001, IMO-2125 or tilsotolimod, AST-008 or cavrotolimod, MGN1703 or lefitolimod), CV8102, NKTR-262 plus NKTR-214, LHC165, G100, intralesional interleukin-2, Daromun (L19IL2 plus L19TNF), Hiltonol (poly-ICLC), electroporation including calcium electroporation and plasmid..."

Journal • Review • Gene Therapies • Immune Modulation • Inflammation • Melanoma • Oncology • Solid Tumor • CD40 • IL12A • MAGEA3 • TYRP1

REVEAL: A Study of NKTR-262 in Combination With Bempegaldesleukin (NKTR-214) and With Bempegaldesleukin Plus Nivolumab in Patients With Locally Advanced or Metastatic Solid Tumor Malignancies (clinicaltrials.gov) - P1/2; N=64; Active, not recruiting; Sponsor: Nektar Therapeutics; Trial completion date: Dec 2022 ➔ Dec 2021

Clinical • Combination therapy • Trial completion date • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Melanoma • Merkel Cell Carcinoma • Neuroendocrine Tumor • Non-melanoma Skin Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • PD-1 • PD-L1

REVEAL: A Study of NKTR-262 in Combination With Bempegaldesleukin (NKTR-214) and With Bempegaldesleukin Plus Nivolumab in Patients With Locally Advanced or Metastatic Solid Tumor Malignancies (clinicaltrials.gov) - P1/2; N=64; Active, not recruiting; Sponsor: Nektar Therapeutics; N=393 ➔ 64

Clinical • Combination therapy • Enrollment change • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Melanoma • Merkel Cell Carcinoma • Neuroendocrine Tumor • Non-melanoma Skin Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • PD-1 • PD-L1

Nektar Therapeutics to Host Webcast Conference Call for Analysts & Investors with Expert Oncologist Panel During 2020 Society for Immunotherapy of Cancer (SITC) 35th Annual Meeting (PRNewswire) - "The event will follow the SITC 2020 presentations on Wednesday which will include clinical data for three Nektar-sponsored studies, including updated clinical data from a cohort of first-line Stage IV metastatic melanoma patients in the PIVOT-02 study of bempegaldesleukin (NKTR-214; BEMPEG) with nivolumab, as well as presentations about Nektar's NKTR-255 and NKTR-262 programs. The 2020 SITC Annual Meeting is being held virtually from November 9 to November 14, 2020....Abstract 368...Abstract 420...Adi Diab..."

Clinical data • Hematological Malignancies • Melanoma • Oncology

Nektar Therapeutics Reports Third Quarter 2020 Financial Results (Nektar Therapeutics Press Release) - "...'We are also pleased to report that we are ahead of our enrollment targets for the Phase 2 PROPEL study of bempegaldesleukin with pembrolizumab in patients with metastatic non-small cell lung cancer and we look forward to sharing the initial data from this important study in the first part of 2021...Next week's 2020 SITC meeting will feature data presentations that showcase the strength of Nektar's immune-oncology pipeline, including an oral presentation of 2 1/2 year data for metastatic melanoma patients treated with bempegaldesleukin plus nivolumab, and promising early data for NKTR-255, our IL-15 cytokine, as well as NKTR-262, our TLR agonist program'...REVEAL:...Adi Diab..."

Clinical data • Enrollment status • P1/2 data • P2 data • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology

REVEAL: A Study of NKTR-262 in Combination With Bempegaldesleukin (NKTR-214) and With Bempegaldesleukin Plus Nivolumab in Patients With Locally Advanced or Metastatic Solid Tumor Malignancies (clinicaltrials.gov) - P1/2; N=393; Active, not recruiting; Sponsor: Nektar Therapeutics; Recruiting ➔ Active, not recruiting

Clinical • Combination therapy • Enrollment closed • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Melanoma • Merkel Cell Carcinoma • Neuroendocrine Tumor • Non-melanoma Skin Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • PD-1 • PD-L1

Enhancing Antigen Presentation With NKTR-262 Shows Early Efficacy in Phase 1 Trial (Cancer Therapy Advisor) - "Adi Diab...concluded that 'NKTR-262 intratumoral, as monotherapy or in combination, showed early signs of clinical activity and an acceptable safety profile in this highly relapsed/refractory melanoma patient population.'"

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SITC 2020 - 35th Anniversary Annual Meeting (Accelerating Cancer Immunotherapy) - "Clinical trials of combinatorial therapies: Adi Diab...REVEAL: Phase 1 Dose Escalation Study of NKTR 262, a Novel TLR7/8 Agonist, Plus Bempegaldesleukin: Local Innate Immune Activation and Systemic Adaptive Immune Expansion for Treating Solid Tumors...John Thompson...Phase I/Ib first in human study of NIZ985 (HetIL 15; IL 15/IL 15Ralpha) alone and in combination with spartalizumab, in adults with advanced and metastatic solid tumor...Invigorated by the success of checkpoint therapy with atezolizumab in the IMpassion130 trial in triple negative breast cancer (TNBC), a series of studies in the neoadjuvant setting for breast cancer have been initiated. Some of the rationale and the results of these were reviewed by Elizabeth Mittendorf."

SITC 2020: Positive clinical data for combination therapies for melanoma and lung cancer - "'Despite the tremendous success we have seen with immunotherapy in treating patients with advanced melanoma, current therapies are not effective in all patients. We have an unmet clinical need for new therapies that can bring sustained benefit to more patients,' said Diab. 'The safety profile and sustained response to this combination therapy are encouraging and we look forward to further evaluation in the Phase III trials that are now starting,' said Diab."

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[VIRTURL] REVEAL: Phase 1 dose-escalation study of NKTR-262, a novel TLR7/8 agonist, plus bempegaldesleukin: local innate immune activation and systemic adaptive immune expansion for treating solid tumors (SITC 2020) - No abstract available

P1 data • Oncology • Solid Tumor