Safety and Clinical Activity of Nivatrotamab, an Anti GD2×CD3 Bispecific Antibody, in Relapsed/Recurrent Metastatic Small-cell Lung Cancer An Open-label, Single-arm, Multicenter, Phase 1/2 Trial

Adult patients with small-cell lung cancer (SCLC) will be treated with nivatrotamab a monoclonal anti GD2×CD3 bispecific antibody to investigate the safety and tolerability of the drug.

Start Date17 Aug 2021

Sponsor / Collaborator

Y-mAbs Therapeutics, Inc.

NCT03189706 / Active, not recruitingEarly Phase 1IIT

Phase II Study of Hu3F8, Irinotecan/Temozolomide and Sargramostim (HITS) Chemoimmunotherapy for High-Risk Neuroblastoma

The purpose of this study is to find out whether an experimental drug called Hu3F8 can be given with the chemotherapy drugs irinotecan and temozolomide and another drug called GM-CSF. The investigators want to find out if this combination is safe and what effect it has on the participant and the disease.

Start Date12 Jun 2017

Sponsor / Collaborator

Memorial Sloan Kettering Cancer Center

[+1]

NCT03033303 / Active, not recruitingPhase 2IIT

Hu3F8/GM-CSF Immunotherapy Plus Isotretinoin for Consolidation of First Remission of Patients With High-Risk Neuroblastoma: A Phase II Study

The purpose of this study is to test see the combined effects of the study drug called Humanized 3F8 (Hu3F8) when used with granulocyte-macrophage colony stimulating factor (GM-CSF). Hu3F8 plus GM-CSF could prevent your neuroblastoma from growing, but it could also cause side effects.

Start Date23 Jan 2017

Sponsor / Collaborator

Memorial Sloan Kettering Cancer Center

[+1]

100 Clinical Results associated with Nivatrotamab

100 Translational Medicine associated with Nivatrotamab

100 Patents (Medical) associated with Nivatrotamab

Literatures (Medical) associated with Nivatrotamab

01 Jul 2021·Pediatric blood & cancerQ3 · MEDICINE

Potent antitumor effect of T cells armed with anti‐GD2 bispecific antibody

Q3 · MEDICINE

Article

Author: Guo, Hong‐fen ; Xu, Hong ; Cheung, Nai‐Kong V. ; Hoseini, Sayed Shahabuddin ; Nakajima, Miho ; Suzuki, Maya

Abstract:

Background:

Humanized 3F8‐bispecific antibody (hu3F8‐BsAb) using the IgG(L)‐scFv format (where scFv is single‐chain variable fragment), where the anti‐CD3 huOKT3 scFv is fused with the carboxyl end of the hu3F8 light chain, has potent antitumor cytotoxicity against GD2(+) tumors. To overcome the insufficient number and function of T cells in cancer patients, they can be rejuvenated and expanded ex vivo before arming with hu3F8‐BsAb for adoptive transfer, potentially reducing toxic side effects from direct BsAb administration.

Procedure:

T cells from normal volunteers were expanded and activated ex vivo using CD3/CD28 beads for 8 days. Activated T cells (ATCs) were harvested and co‐incubated with a Good Manufacturing Practice grade hu3F8‐BsAb at room temperature for 20 min. These armed ATCs were tested for cytotoxicity in vitro and in vivo against human GD2(+) cell lines and patient‐derived xenografts in BALB‐Rag2−/−IL‐2R‐γc‐KO mice.

Results:

Hu3F8‐BsAb armed ATCs showed robust antigen‐specific tumor cytotoxicity against GD2(+) tumors in vitro. In vivo, T cells armed with hu3F8‐BsAb were highly cytotoxic against GD2(+) melanoma and neuroblastoma xenografts in mice, accompanied by T‐cell infiltration without significant side effects. Only zeptomole (10−21) quantities of BsAb per T cell was required for maximal antitumor effects. Tumor response was a function of T‐cell dose.

Conclusion:

BsAb armed T cells may have clinical utility as the next generation of cytotherapy combined with recombinant BsAb against human tumors for both adult and pediatrics, if autologous T cells can be activated and expanded ex vivo.

01 Jan 2020·TheranosticsQ1 · MEDICINE

Alpha radioimmunotherapy using ²²⁵Ac-proteus-DOTA for solid tumors - safety at curative doses

Q1 · MEDICINE

ArticleOA

Author: Vargas, Daniela Burnes ; Patel, Mitesh ; Cheal, Sarah M ; Yang, Guangbin ; Bell, Meghan ; Cheung, Nai-Kong V ; Scheinberg, David A ; Veach, Darren R ; Guo, Hong-Fen ; Ahad, Afruja ; McDevitt, Michael R ; Michel, Adam O ; Ouerfelli, Ouathek ; Fung, Edward K ; Piersigilli, Alessandra ; Punzalan, Blesida ; Larson, Steven M ; Monette, Sébastien ; Santich, Brian H ; Pillarsetty, Naga Vara Kishore ; Xu, Hong

This is the initial report of an α-based pre-targeted radioimmunotherapy (PRIT) using ²²⁵Ac and its theranostic pair, ¹¹¹In. We call our novel tumor-targeting DOTA-hapten PRIT system "proteus-DOTA" or "Pr." Herein we report the first results of radiochemistry development, radiopharmacology, and stoichiometry of tumor antigen binding, including the role of specific activity, anti-tumor efficacy, and normal tissue toxicity with the Pr-PRIT approach (as α-DOTA-PRIT). A series of α-DOTA-PRIT therapy studies were performed in three solid human cancer xenograft models of colorectal cancer (GPA33), breast cancer (HER2), and neuroblastoma (GD2), including evaluation of chronic toxicity at ~20 weeks of select survivors. Methods: Preliminary biodistribution experiments in SW1222 tumor-bearing mice revealed that ²²⁵Ac could not be efficiently pretargeted with current DOTA-Bn hapten utilized for ¹⁷⁷Lu or ⁹⁰Y, leading to poor tumor uptake in vivo. Therefore, we synthesized Pr consisting of an empty DOTA-chelate for ²²⁵Ac, tethered via a short polyethylene glycol linker to a lutetium-complexed DOTA for picomolar anti-DOTA chelate single-chain variable fragment (scFv) binding. Pr was radiolabeled with ²²⁵Ac and its imaging surrogate, ¹¹¹In. In vitro studies verified anti-DOTA scFv recognition of [²²⁵Ac]Pr, and in vivo biodistribution and clearance studies were performed to evaluate hapten suitability and in vivo targeting efficiency. Results: Intravenously (i.v.) administered ²²⁵Ac- or ¹¹¹In-radiolabeled Pr in mice showed rapid renal clearance and minimal normal tissue retention. In vivo pretargeting studies show high tumor accumulation of Pr (16.71 ± 5.11 %IA/g or 13.19 ± 3.88 %IA/g at 24 h p.i. for [²²⁵Ac]Pr and [¹¹¹In]Pr, respectively) and relatively low uptake in normal tissues (all average ≤ 1.4 %IA/g at 24 h p.i.). Maximum tolerated dose (MTD) was not reached for either [²²⁵Ac]Pr alone or pretargeted [²²⁵Ac]Pr at administered activities up to 296 kBq/mouse. Single-cycle treatment consisting of α-DOTA-PRIT with either huA33-C825 bispecific anti-tumor/anti-DOTA-hapten antibody (BsAb), anti-HER2-C825 BsAb, or hu3F8-C825 BsAb for targeting GPA33, HER2, or GD2, respectively, was highly effective. In the GPA33 model, no complete responses (CRs) were observed but prolonged overall survival of treated animals was 42 d for α-DOTA-PRIT vs. 25 d for [²²⁵Ac]Pr only (P < 0.0001); for GD2, CRs (7/7, 100%) and histologic cures (4/7, 57%); and for HER2, CRs (7/19, 37%) and histologic cures (10/19, 56%) with no acute or chronic toxicity. Conclusions: [²²⁵Ac]Pr and its imaging biomarker [¹¹¹In]Pr demonstrate optimal radiopharmacologic behavior for theranostic applications of α-DOTA-PRIT. For this initial evaluation of efficacy and toxicity, single-cycle treatment regimens were performed in all three systems. Histologic toxicity was not observed, so MTD was not observed. Prolonged overall survival, CRs, and histologic cures were observed in treated animals. In comparison to RIT with anti-tumor IgG antibodies, [²²⁵Ac]Pr has a much improved safety profile. Ultimately, these data will be used to guide clinical development of toxicity and efficacy studies of [²²⁵Ac]Pr, with the goal of delivering massive lethal doses of radiation to achieve a high probability of cure without toxicity.

01 Mar 2015·Cancer immunology researchQ1 · MEDICINE

Retargeting T Cells to GD2 Pentasaccharide on Human Tumors Using Bispecific Humanized Antibody

Q1 · MEDICINE

Article

Author: Huse, Morgan ; Xu, Hong ; Cheung, Nai-Kong V. ; Cheng, Ming ; Chen, Yuedan ; Guo, Hongfen

Abstract:

Anti-disialoganglioside GD2 IgG antibodies have shown clinical efficacy in solid tumors that lack human leukocyte antigens (e.g., neuroblastoma) by relying on Fc-dependent cytotoxicity. However, there are pain side effects secondary to complement activation. T-cell retargeting bispecific antibodies (BsAb) also have clinical potential, but it is thus far only effective against liquid tumors. In this study, a fully humanized hu3F8-BsAb was developed, in which the anti-CD3 huOKT3 single-chain Fv fragment (ScFv) was linked to the carboxyl end of the anti-GD2 hu3F8 IgG1 light chain, and was aglycosylated at N297 of Fc to prevent complement activation and cytokine storm. In vitro, hu3F8-BsAb activated T cells through classic immunologic synapses, inducing GD2-specific tumor cytotoxicity at femtomolar EC50 with >105-fold selectivity over normal tissues, releasing Th1 cytokines (TNFα, IFNγ, and IL2) when GD2(+) tumors were present. In separate murine neuroblastoma and melanoma xenograft models, intravenous hu3F8-BsAb activated T cells in situ and recruited intravenous T cells for tumor ablation, significantly prolonging survival from local recurrence or from metastatic disease. Hu3F8-BsAb, but not control BsAb, drove T cells and monocytes to infiltrate tumor stroma. These monocytes were necessary for sustained T-cell proliferation and/or survival and contributed significantly to the antitumor effect. The in vitro and in vivo antitumor properties of hu3F8-BsAb and its safety profile support its further clinical development as a cancer therapeutic, and provide the rationale for exploring aglycosylated IgG-scFv as a structural platform for retargeting human T cells. Cancer Immunol Res; 3(3); 266–77. ©2014 AACR.

News (Medical) associated with Nivatrotamab

25 Feb 2021

·www.globenewswire.com

Y-mAbs Announces 2020 Financial Results and Recent Corporate Developments

NEW YORK, Feb. 25, 2021 (GLOBE NEWSWIRE) -- Y-mAbs Therapeutics, Inc. (the “Company” or “Y-mAbs”) (Nasdaq: YMAB) a development-stage clinical biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer, today reported financial results for 2020. “We are pleased with our 2020 financial results, especially seen in conjunction with the approval of DANYELZA, and the sale of our Priority Review Voucher for $105 million. For omburtamab, we are working closely with the FDA to address the Agency’s request for additional data, and we believe we have made progress and continue to work very hard on resubmitting the BLA. We also entered into a licensing agreement for Greater China for DANYELZA and omburtamab including milestones of up to $120 million and distribution agreements for DANYELZA and omburtamab for Eastern Europe, Russia and Israel, and thereby secured expanded access for children around the world to this important immunotherapy,” stated Thomas Gad, founder, Chairman and President. Dr. Claus Moller, Chief Executive Officer, continued, “We successfully completed a follow-on offering with gross proceeds of approximately $115.0 million earlier this week, and in parallel, we are making good progress in the clinic and have continued to advance the earlier stage programs in our pipeline. Nivatrotamab, our leading bispecific antibody, recently received ODD and RPDD from the FDA and our INDs for nivatrotamab in Small Cell Lung Cancer (Phase 2) and 177Lu-omburtamab-DTPA for medulloblastoma (Phase 1/2) and B7-H3 positive CNS/leptomeningeal metastasis in adults (Phase 1/2) were recently cleared by the FDA.” Fourth Quarter 2020 and Recent Corporate Developments Subsequent to the end of the fourth quarter, on February 17, 2021, Y-mAbs announced the pricing of a follow-on shelf public offering, resulting in gross proceeds to the Company of approximately $115.0 million. On December 28, 2020 Y-mAbs announced that it entered into a definitive agreement to sell its DANYELZA Priority Review Voucher to United Therapeutics Corporation for $105 million. Under the terms of the license agreement with Memorial Sloan Kettering, Y-mAbs will retain 60% of the net proceeds received from the sale. The transaction closed in January 2021. On December 18, 2020, Y-mAbs announced that it had entered into a license agreement with SciClone Pharmaceuticals International Ltd to be the exclusive development and commercialization partner of DANYELZA and omburtamab for the treatment of pediatric patients in China, including upfront, approval and sales milestones of up to $120 million. On December 18, 2020, Y-mAbs announced that it had entered into a distribution agreement with Swixx BioPharma AG to be the exclusive distributor of DANYELZA and omburtamab for the treatment of pediatric patients in Eastern Europe and Russia. On December 9, 2020, Y-mAbs announced an update on DANYELZA data from the Company’s Study 201, which was presented at the ESMO Immunocology-Oncology Virtual Congress 2020. On December 4, 2020, Y-mAbs announced that it had entered into a license and distribution agreement with Takeda Israel for the registration and commercialization of DANYELZA and omburtamab for the treatment of pediatric patients in the State of Israel. On November 25, 2020, Y-mAbs announced that the FDA had approved DANYELZA for the treatment relapsed or primary refractory high-risk neuroblastoma. On November 19, 2020, Y-mAbs announced that a clinical update of omburtamab for the treatment of diffuse intrinsic pontine glioma was presented at the SNO Virtual Annual Meeting. On October 26, 2020, Y-mAbs announced that the FDA had cleared the Company’s IND for 177 Lu-omburtamab-DTPA for the treatment of B7-H3 positive CNS and Leptomeningeal Metastasis from tumors in adult patients. Lu-omburtamab-DTPA for the treatment of B7-H3 positive CNS and Leptomeningeal Metastasis from tumors in adult patients. On October 14, 2020, Y-mAbs announced that the FDA had cleared the Company’s Investigational New Drug application for 177 Lu-omburtamab-DTPA for the treatment of medulloblastoma, which is the most common type of primary brain cancer in children. Lu-omburtamab-DTPA for the treatment of medulloblastoma, which is the most common type of primary brain cancer in children. On October 7, 2020, Y-mAbs announced that the FDA has granted Orphan Drug Designation and Rare Pediatric Disease Designation for its leading bispecific antibody product candidate, nivatrotamab, for the treatment of neuroblastoma. On October 5, 2020, Y-mAbs announced that it had received a Refusal to File letter from the FDA for the omburtamab BLA for the treatment of pediatric patients with CNS/leptomeningeal metastasis from neuroblastoma. Subsequently, Y-mAbs has been in close dialog with the Agency to amend the BLA with the goal of resubmitting by the end of the second quarter or in the third quarter 2021. Financial Results Y-mAbs reported a net loss of $119.3 million, or ($2.97) per basic and diluted share, for the year ended December 31, 2020, compared to a net loss of $81.0 million, or ($2.30) per basic and diluted share, reported for the year ended December 31, 2019. Revenues and Related Royalties Expense Y-mAbs reported net revenues of $20.8 million for the year ended December 31, 2020 related to its licensing agreements in China and Israel. No revenues were reported for the year ended December 31, 2019. Additionally, there were $2.2 million in royalties expense associated with the license revenue reported for the year ended December 31, 2020. No royalties expense was reported for the year ended December 31, 2019. Operating Expenses Research and Development Research and development expenses were $93.7 million for the twelve months ended December 31, 2020, compared to $63.5 million for the twelve months ended December 31, 2019, an increase of $30.2 million. The increase in research and development expenses primarily reflects the following: $13.4 million increase in personnel costs; $13.2 million increase in milestones and license acquisition cost; $1.1 million increase in professional and consulting fees; and $1.6 million increase in outsourced services and supplies costs. General and Administration General and administrative expenses were $44.8 million for the twelve months ended December 31, 2020, compared to $19.5 million for the twelve months ended December 31, 2019, an increase of $25.3 million. The increase in general and administrative expenses primarily reflects the following: $12.7 million increase in commercial infrastructure costs; $8.9 million increase in personnel costs; $2.1 million increase in business insurance; and $2.1 million in professional fees. Cash and Cash Equivalents The Company had approximately $114.6 million in cash and cash equivalents as of December 31, 2020. Webcast and Conference Call The Company will host a conference call on Friday, February 26, 2021 at 9 a.m. Eastern Time. To participate in the call, please dial 877-407-0792 (domestic) or 201-689-8263 (international) and reference the access code 13716724. A webcast will be available at: About Y-mAbs Y-mAbs is a commercial-stage biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer. The Company has a broad and advanced product pipeline, including one FDA approved product, DANYELZA® (naxitamab-gqgk), which targets tumors that express GD2, and one pivotal-stage product candidate, omburtamab, which targets tumors that express B7-H3. Forward-Looking Statements Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute “forward-looking statements” within the meaning of The Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to, statements about our business model and development, commercialization and product distribution plans; current and future clinical and pre-clinical studies and our research and development programs; expectations related to the timing of the initiation and completion of regulatory submissions; regulatory, marketing and reimbursement approvals; rate and degree of market acceptance and clinical utility as well as pricing and reimbursement levels; retaining and hiring key employees; our commercialization, marketing and manufacturing capabilities and strategy; our intellectual property position and strategy; additional product candidates and technologies; collaborations or strategic partnerships and the potential benefits thereof; expectations related to the use of our cash and cash equivalents, and the need for, timing and amount of any future financing transaction; our financial performance, including our estimates regarding revenues, expenses, capital expenditure requirements; developments relating to our competitors and our industry; and other statements that are not historical facts. Words such as ‘‘anticipate,’’ ‘‘believe,’’ “contemplate,” ‘‘continue,’’ ‘‘could,’’ ‘‘estimate,’’ ‘‘expect,’’ “hope,” ‘‘intend,’’ ‘‘may,’’ ‘‘might,’’ ‘‘plan,’’ ‘‘potential,’’ ‘‘predict,’’ ‘‘project,’’ ‘‘should,’’ ‘‘target,’’ “will”, ‘‘would’’ and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Our product candidates and related technologies are novel approaches to cancer treatment that present significant challenges. Actual results may differ materially from those indicated by such forward-looking statements as a result of various factors, including but not limited to: risks associated with our financial condition and need for additional capital; risks associated with our development work; cost and success of our product development activities and clinical trials; the risks of delay in the timing of our regulatory submissions or failure to receive approval of our drug candidates; the risks related to commercializing any approved pharmaceutical product including the rate and degree of market acceptance of our product candidates; development of our sales and marketing capabilities and risks associated with failure to obtain sufficient reimbursement for our products; the risks related to our dependence on third parties including for conduct of clinical testing and product manufacture; our inability to enter into partnerships; the risks related to government regulation; risks related to market approval, risks associated with protection of our intellectual property rights; risks related to employee matters and managing growth; risks related to our common stock, risks associated with the pandemic caused by the novel coronavirus known as COVID-19 and other risks and uncertainties affecting the Company including those described in the "Risk Factors" section included in our Annual Report on Form 10-K and in our other SEC filings. Any forward-looking statements contained in this press release speak only as of the date hereof, and the Company undertakes no obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise. “DANYELZA” and “Y-mAbs” are registered trademarks of Y-mAbs Therapeutics, Inc. Contact: Y-mAbs Therapeutics, Inc. 230 Park Avenue, Suite 3350 New York, NY 10169 USA +1 646 885 8505 E-mail: info@ymabs.com

CollaborateFinancial StatementAntibodyOrphan DrugImmunotherapy

100 Deals associated with Nivatrotamab

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Small cell lung cancer recurrent	Phase 2	US	Y-mAbs Therapeutics, Inc.	17 Aug 2021
Small Cell Carcinoma	Phase 2	-	Y-mAbs Therapeutics, Inc.	01 May 2021
Solid tumor	Phase 2	US	Y-mAbs Therapeutics, Inc.	22 Feb 2019
Osteosarcoma	Phase 2	US	Y-mAbs Therapeutics, Inc.	22 Feb 2019
Neuroblastoma	Phase 2	US	Y-mAbs Therapeutics, Inc.	23 Jan 2017
Neuroblastoma	Phase 2	US	Memorial Sloan Kettering Cancer Center	23 Jan 2017
Ewing Sarcoma	Preclinical	US	Y-mAbs Therapeutics, Inc.	-

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04750239 (CTgov)	Phase 1/2	Small cell lung cancer recurrent	3	Nivatrotamab	bnfnphbyjg(yjsrprswpc) = umpcovobge lgtaqoczgg (nzwjsbdvwo, gudlagvufi - wrbfbxfqvs) View more	-	14 Aug 2023

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