The goal of this clinical trial is to test MGC018 in patients with relapsed or refractory Extensive-Stage Small-Cell Lung Cancer (ES-SCLC). The main question it aims to answer is:
• Does the administration of MGC018 achieve a clinically meaningful response rate of 25% in patients with relapsed or refractory ES-SCLC?
Participants enrolled in the trial will receive MGC018 through an intravenous (IV) infusion, every 28 days until disease progression or unacceptable toxicity. Tumor assessment will be done every 2 cycles (28 day cycles). Blood samples will be taken for biomarker analysis before treatment, on cycle 3 day 1, and at progression. A pretreatment biopsies will be done.

Start Date15 Apr 2024

Sponsor / Collaborator

Georgetown University Hospital

[+1]

NCT05551117

/ CompletedPhase 2

A Phase 2, Open-label, Study of Vobramitamab Duocarmazine in Participants With Metastatic Castration-resistant Prostate Cancer and Other Solid Tumors

Study CP-MGC018-03 is an open-label, two-part, Phase 2 study. Part 1 of the study will enroll participants with metastatic castration-resistant prostate cancer (mCRPC) previously treated with one prior androgen receptor axis-targeted therapy (ARAT). ARAT includes abiraterone, enzalutamide, or apalutamide.
Participants may have received up to 1 prior docetaxel-containing regimen, but no other chemotherapy agents.
This part of the study will assess the efficacy and tolerability of vobramitamab duocarmazine (MGC018) in two experimental arms (2.0 mg/kg every 4 weeks [Q4W] and 2.7 mg/kg Q4W) . Approximately 100 participants will be randomized 1:1.
Part 2 of the study will enroll participants with locally advanced or metastatic solid tumors. Participants must have progressive following at least 1 prior line of standard chemotherapy for advanced or metastatic disease. Participants will receive vobramitamab duocarmazine at a dose of 2.7 mg/kg every 4 weeks. Up to 200 participants may be enrolled in Part 2.
In both parts, vobramitamab duocarmazine will be administered intravenously (IV) in clinic on Day 1 of each 4-week cycle. Vobramitamab duocarmazine will be administered until criteria for treatment discontinuation are met. Participants will undergo regular testing for signs of disease progression using computed tomography (CT) scans, magnetic resonance imaging (MRI), bone scans, and prostate-specific antigen (PSA) blood tests. Routine examinations and blood tests will be performed and evaluated by the study doctor.

Start Date13 Jun 2023

Sponsor / Collaborator

MacroGenics, Inc.

NCT05293496

/ Active, not recruitingPhase 1

A Phase 1/1b Dose Escalation and Cohort Expansion Study of MGC018 in Combination With Checkpoint Inhibitor in Participants With Advanced Solid Tumors

Study CP-MGC018-02 is a study of vobramitamab duocarmazine (MGC018) in combination with lorigerlimab (MGD019). The study is designed to characterize safety, tolerability, pharmacokinetics (PK), immunogenicity, pharmacodynamics, and preliminary antitumor activity. Participants with relapsed or refractory, unresectable, locally advanced or metastatic solid tumors including, but not limited to, metastatic castration-resistant prostate cancer (mCRPC), melanoma, pancreatic cancer, hepatocellular carcinoma (HCC), ovarian cancer, and renal cell carcinoma (RCC) will be enrolled.
Vobramitamab duocarmazine and lorigerlimab are administered separately on Day 1 of every 4-week (28-day) cycle at the assigned dose for each cohort. Participants who do not meet criteria for study drug discontinuation may receive study drugs for up to 2 years.
Tumor assessments are performed every 8 weeks (± 7 days) for the initial 6 months on study drugs, then every 12 weeks (± 21 days) until progressive disease (PD).
Participants will be followed for safety throughout the study. .

Start Date19 Apr 2022

Sponsor / Collaborator

MacroGenics, Inc.

100 Clinical Results associated with vobramitamab duocarmazine

100 Translational Medicine associated with vobramitamab duocarmazine

100 Patents (Medical) associated with vobramitamab duocarmazine

Literatures (Medical) associated with vobramitamab duocarmazine

01 Sep 2023·Journal for immunotherapy of cancer

Antitumor activity of the investigational B7-H3 antibody-drug conjugate, vobramitamab duocarmazine, in preclinical models of neuroblastoma

Article

Author: Bonvini, Ezio ; Bensa, Veronica ; Giusto, Elena ; Corrias, Maria Valeria ; Cilli, Michele ; Ciampi, Eleonora ; Calarco, Enzo ; Loo, Derik ; Brignole, Chiara ; Perri, Patrizia ; Pastorino, Fabio ; Ponzoni, Mirco ; Astigiano, Simonetta

Introduction:

B7-H3 is a potential target for pediatric cancers, including neuroblastoma (NB). Vobramitamab duocarmazine (also referred to as MGC018 and herein referred to as vobra duo) is an investigational duocarmycin-based antibody-drug conjugate (ADC) directed against the B7-H3 antigen. It is composed of an anti-B7-H3 humanized IgG1/kappa monoclonal antibody chemically conjugated through a cleavable valine-citrulline linker to aduocarmycin-hydroxybenzamideazaindole (vc-seco-DUBA). Vobra duo has shown preliminary clinical activity in B7-H3-expressing tumors.

Methods:

B7-H3 expression was evaluated by flow-cytometry in a panel of human NB cell lines. Cytotoxicity was evaluated in monolayer and in multicellular tumor spheroid (MCTS) models by the water-soluble tetrazolium salt,MTS, proliferation assay and Cell Titer Glo 3D cell viability assay, respectively. Apoptotic cell death was investigated by annexin V staining. Orthotopic, pseudometastatic, and resected mouse NB models were developed to mimic disease conditions related to primary tumor growth, metastases, and circulating tumor cells with minimal residual disease, respectively.

Results:

All human NB cell lines expressed cell surface B7-H3 in a unimodal fashion. Vobra duo was cytotoxic in a dose-dependent and time-dependent manner against all cell lines (IC50 range 5.1–53.9 ng/mL) and NB MCTS (IC50 range 17.8–364 ng/mL). Vobra duo was inactive against a murine NB cell line (NX-S2) that did not express human B7-H3; however, NX-S2 cells were killed in the presence of vobra duo when co-cultured with human B7-H3-expressing cells, demonstrating bystander activity. In orthotopic and pseudometastatic mouse models, weekly intravenous treatments with 1 mg/kg vobra duo for 3 weeks delayed tumor growth compared with animals treated with an irrelevant (anti-CD20) duocarmycin-ADC. Vobra duo treatment for 4 weeks further increased survival in both orthotopic and resected NB models. Vobra duo compared favorably to TOpotecan-TEMozolomide (TOTEM), the standard-of-care therapy for NB relapsed disease, with tumor relapse delayed or arrested by two or three repeated 4-week vobra duo treatments, respectively. Further increased survival was observed in mice treated with vobra duo in combination with TOTEM. Vobra duo treatment was not associated with body weight loss, hematological toxicity, or clinical chemistry abnormalities.

Conclusion:

Vobra duo exerts relevant antitumor activity in preclinical B7-H3-expressing NB models and represents a potential candidate for clinical translation.

01 Nov 2020·Molecular cancer therapeuticsQ2 · MEDICINE

Preclinical Development of MGC018, a Duocarmycin-based Antibody–drug Conjugate Targeting B7-H3 for Solid Cancer

Q2 · MEDICINE

Article

Author: Loo, Deryk ; Moore, Paul A. ; Koenig, Scott ; Huang, Ling ; Li, Ying ; Li, Pam ; Tamura, James ; Ciccarone, Valentina ; Chen, Francine Z. ; Gaynutdinov, Timur ; Sharma, Sharad ; Yee-Toy, Nicholas C. ; De Costa, Anushka ; Chiechi, Michael ; Hotaling, Tim E. ; Son, Thomas ; Brown, Jennifer G. ; Hooley, Jeff ; Gorlatov, Sergey ; Barat, Bhaswati ; Chen, Yan ; Wolff, Christina R. ; Li, Hua ; Easton, Ann ; Scribner, Juniper A. ; Bonvini, Ezio

Abstract:

B7-H3, also referred to as CD276, is a member of the B7 family of immune regulatory proteins. B7-H3 is overexpressed on many solid cancers, including prostate cancer, renal cell carcinoma, melanoma, squamous cell carcinoma of the head and neck, non–small cell lung cancer, and breast cancer. Overexpression of B7-H3 is associated with disease severity, risk of recurrence and reduced survival. In this article, we report the preclinical development of MGC018, an antibody–drug conjugate targeted against B7-H3. MGC018 is comprised of the cleavable linker-duocarmycin payload, valine-citrulline-seco duocarmycin hydroxybenzamide azaindole (vc-seco-DUBA), conjugated to an anti-B7-H3 humanized IgG1/kappa mAb through reduced interchain disulfides, with an average drug-to-antibody ratio of approximately 2.7. MGC018 exhibited cytotoxicity toward B7-H3–positive human tumor cell lines, and exhibited bystander killing of target-negative tumor cells when cocultured with B7-H3–positive tumor cells. MGC018 displayed potent antitumor activity in preclinical tumor models of breast, ovarian, and lung cancer, as well as melanoma. In addition, antitumor activity was observed toward patient-derived xenograft models of breast, prostate, and head and neck cancer displaying heterogeneous expression of B7-H3. Importantly, MGC018 exhibited a favorable pharmacokinetic and safety profile in cynomolgus monkeys following repeat-dose administration. The antitumor activity observed preclinically with MGC018, together with the positive safety profile, provides evidence of a potentially favorable therapeutic index and supports the continued development of MGC018 for the treatment of solid cancers.

News (Medical) associated with vobramitamab duocarmazine

21 Mar 2025

·www.fiercebiotech.com

MacroGenics pulls plug on vobra duo ADC after seeing phase 2 prostate cancer data

Despite giving up on vobra duo, MacroGenics CEO Scott Koenig, M.D., Ph.D., said that the company still believes B7-H3 has “potential” as a target.\n MacroGenics has made the final decision to abandon work on one of its more advanced antibody-drug conjugates after taking a look at the latest phase 2 data.The biotech had already paused work on vobramitamab duocarmazine (vobra duo) back in November, explaining that it was awaiting progression-free survival (PFS) data from a phase 2 monotherapy prostate cancer trial. Vobra duo has a cleavable peptide linker designed to deliver a DNA-alkylating duocarmycin payload to solid tumors that express B7-H3.CEO Scott Koenig, M.D., Ph.D., explained to investors at the time that the company would make a call on whether to invest further in vobra duo after considering the final PFS data, the therapy’s safety profile and the competitive landscape in the context of the rest of its pipeline.The results are now in, and they show a median radiographic PFS of 9.5 months and 10 months for the 2-mg/kg and 2.7-mg/kg doses, respectively. Safety data “remained consistent with prior data disclosures,” MacroGenics said in its full-year earnings results March 20.“Based on its assessment of the vobra duo safety and efficacy profile and an internal resource and portfolio review, MacroGenics has decided not to pursue further internal development of vobra duo and will instead explore potential alternatives for partnering this program,” the company said in the release.Despite giving up on vobra duo, Koenig said the company still believes B7-H3 has “potential” as a target, adding that the biotech is “pleased with the progress being made with our alternate anti-B7-H3 ADC, MGC026.” MGC026, which is a TOP1i-based ADC, is undergoing a phase 1 dose-escalation study in patients with advanced solid tumors. The biotech also has another ADC in the clinic in the form of MGC028, a TOP1i-based ADC that targets ADAM9 and recently started a phase 1 study in solid tumors.MacroGenics is awaiting a readout later this year for lorigerlimab, a PD-1xCTLA-4 bispecific that the company is testing in a phase 2 prostate cancer trial in combination with docetaxel.“We concluded 2024 with the achievement of multiple clinical development milestones, including the completion of enrollment in the LORIKEET phase 2 study evaluating lorigerlimab in combination with docetaxel in patients with mCRPC,” Koenig said in yesterday\'s postmarket release.“We look forward to building upon this momentum in 2025 as we work to advance our novel pipeline of clinical product candidates, including lorigerlimab, MGC026 and MGC028,” the CEO added.MacroGenics entered the year with $201.7 million in the bank, which the company expects to last into the second half of 2026.

Phase 1ADCPhase 2

06 Nov 2024

·firstwordpharma.com

MacroGenics' ADC moves one step closer to the drug development graveyard

MacroGenics is pulling back even further on the reins of lead antibody-drug conjugate (ADC) vobramitamab duocarmazine (vobra duo). The biotech said in its quarterly earnings report Tuesday that development of the B7-H3-targeting ADC is officially paused until it has complete safety and efficacy data from the Phase II TAMARACK study in-hand.Whether those results will support continued work on vobra duo, formerly MGC018, remains to be seen. Patient dosing in TAMARACK, which had been enrolling individuals with metastatic castration-resistant prostate cancer (mCRPC), was paused in July shortly after the company reported five patient deaths in the trial. MacroGenics expects to have mature median progression-free survival data from TAMARACK in early 2025.Stopped studiesThe development pause affects a Phase I/II trial of the ADC in solid tumours other than mCRPC, including non–small-cell lung cancer, triple-negative breast cancer, squamous cell carcinoma of the head and neck, and melanoma.A Phase I combination study of vobra duo plus MacroGenics' experimental PD-1/CTLA-4 bispecific lorigerlimab will also remain on hold. That trial was enrolling patients with relapsed or refractory, unresectable, locally advanced or metastatic solid tumours.MacroGenics said that, in addition to the TAMARACK safety and efficacy data, its development decision on vobra duo will be based on the competitive landscape for mCRPC, clinical resource availability, and potential partnering opportunities for the ADC.

ADCPhase 1Phase 2Clinical Trial Termination

30 Oct 2024

·www.globenewswire.com

MacroGenics Announces Leadership Transition

Scott Koenig, M.D., Ph.D., to step down as President and CEOBoard to initiate search process to identify new CEO ROCKVILLE, MD, Oct. 30, 2024 (GLOBE NEWSWIRE) -- MacroGenics, Inc. (NASDAQ: MGNX), a biopharmaceutical company focused on discovering, developing, manufacturing and commercializing innovative antibody-based therapeutics for the treatment of cancer, today announced that Scott Koenig, M.D., Ph.D., intends to step down as President and Chief Executive Officer early next year. The Company’s Board of Directors has retained Heidrick & Struggles to lead a search process to identify its next Chief Executive Officer and has established a special committee of the Board to oversee the transition process. William Heiden, Chairman of the Board of Directors said, “Scott was a co-founder of MacroGenics twenty-four years ago and the Company has achieved many milestones under his leadership – including several partnered or company-owned FDA approved monoclonal antibody therapeutics developed by the company. On behalf of the Board, I want to thank Scott for his incredible dedication to the Company’s mission of discovering and developing novel therapeutics to improve patient care.” Mr. Heiden continued, “Today, MacroGenics has several innovative antibody-based therapeutics in development for the treatment of cancer, as well as significant alliances with leading pharmaceutical and biotechnology companies to develop and commercialize novel therapeutics. The Company today has a broad portfolio of promising assets and a strong balance sheet, and the Board and Scott agreed that this is the right time to transition to our next phase of leadership. We look forward to continuing to benefit from his perspectives as an advisor and shareholder.” “I am proud of our many achievements since our founding in 2000, in which we built a fully integrated, science-focused biotechnology company and have been successful in discovering, developing, manufacturing, and commercializing novel immunotherapeutics derived from our proprietary Fc-engineered antibody, bi-specific DART molecule, and antibody drug conjugate (ADC) technologies,” said Dr. Koenig. “Since the company’s IPO in 2013, we were able to fund a significant part of the development portfolio through the achievement of over $1 billion of non-dilutive capital via partnerships. Thanks to the incredible passion and dedication of the people at MacroGenics, three novel therapeutics from our pipeline advanced to approval, including MARGENZA® and ZYNYZ® to treat patients with cancer, and TZIELD® for individuals with early-stage Type 1 diabetes, and we have advanced a rich portfolio of clinical and preclinical molecules in development. I am confident that MacroGenics is well positioned in its current mission to address the significant unmet medical needs of patients with cancer. I look forward to continuing to support the Company in its work to achieve its key strategic objectives and create value for all our stakeholders.” About MacroGenics, Inc. MacroGenics is a biopharmaceutical company focused on discovering, developing, manufacturing and commercializing innovative monoclonal antibody-based therapeutics for the treatment of cancer. The Company generates its pipeline of product candidates primarily from its proprietary suite of next-generation antibody-based technology platforms, which have applicability across broad therapeutic domains. The combination of MacroGenics' technology platforms and protein engineering expertise has allowed the Company to generate promising product candidates and enter into several strategic collaborations with global pharmaceutical and biotechnology companies. For more information, please see the Company's website at www.macrogenics.com. MacroGenics, the MacroGenics logo and MARGENZA are trademarks or registered trademarks of MacroGenics, Inc. Cautionary Note on Forward-Looking Statements Any statements in this press release about future expectations, plans and prospects for MacroGenics (“Company”), including statements about the Company’s strategy, future operations, clinical development of and regulatory plans for the Company’s therapeutic candidates, expected timing of the release of final safety and efficacy data, including mature median rPFS and other statements containing the words “subject to”, "believe", “anticipate”, “plan”, “expect”, “intend”, “estimate”, “potential,” “project”, “may”, “will”, “should”, “would”, “could”, “can”, the negatives thereof, variations thereon and similar expressions, or by discussions of strategy constitute forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: risks that TZIELD, vobramitamab duocarmazine, lorigerlimab, ZYNYZ, MARGENZA or any other product candidate’s revenue, expenses and costs may not be as expected, risks relating to TZIELD, vobramitamab duocarmazine, lorigerlimab, ZYNYZ, MARGENZA or any other product candidate’s market acceptance, competition, reimbursement and regulatory actions; future data updates, especially timing and results of mature median radiographic progression-free survival, other efficacy and safety data with respect to vobramitamab duocarmazine; our ability to provide manufacturing services to our customers; the uncertainties inherent in the initiation and enrollment of future clinical trials; the availability of financing to fund the internal development of our product candidates; expectations of expanding ongoing clinical trials; availability and timing of data from ongoing clinical trials; expectations for the timing and steps required in the regulatory review process; expectations for regulatory approvals; expectations of future milestone payments; the impact of competitive products; our ability to enter into agreements with strategic partners and other matters that could affect the availability or commercial potential of the Company's product candidates; business, economic or political disruptions due to catastrophes or other events, including natural disasters, terrorist attacks, civil unrest and actual or threatened armed conflict, or public health crises; costs of litigation and the failure to successfully defend lawsuits and other claims against us; and other risks described in the Company's filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the Company's views only as of the date hereof. The Company anticipates that subsequent events and developments will cause the Company's views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so, except as may be required by law. These forward-looking statements should not be relied upon as representing the Company's views as of any date subsequent to the date hereof. ###

Executive ChangeIPOADC

100 Deals associated with vobramitamab duocarmazine

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Castration-Resistant Prostatic Cancer	Phase 3	United States	MacroGenics, Inc.	11 Jul 2022
Melanoma	Phase 3	United States	MacroGenics, Inc.	11 Jul 2022
Non-Small Cell Lung Cancer	Phase 3	United States	MacroGenics, Inc.	11 Jul 2022
Extensive stage Small Cell Lung Cancer	Phase 2	United States	MacroGenics, Inc.	15 Apr 2024
Anus Neoplasms	Phase 2	United States	MacroGenics, Inc.	13 Jun 2023
Anus Neoplasms	Phase 2	Australia	MacroGenics, Inc.	13 Jun 2023
Anus Neoplasms	Phase 2	Belgium	MacroGenics, Inc.	13 Jun 2023
Anus Neoplasms	Phase 2	France	MacroGenics, Inc.	13 Jun 2023
Anus Neoplasms	Phase 2	Italy	MacroGenics, Inc.	13 Jun 2023
Anus Neoplasms	Phase 2	Poland	MacroGenics, Inc.	13 Jun 2023

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05551117 (TAMARACK, ESMO2024) Manual	Phase 2	Metastatic castration-resistant prostate cancer	176	Vobra duo 2.0 mg/kg	omgkhazwyk(jhkjptbrjt) = mvzexhtcrc kumbmwecdo (znxqlyytqo, 57 - 79) View more	Positive	15 Sep 2024
				Vobra duo 2.7 mg/kg	omgkhazwyk(jhkjptbrjt) = xthixykqqu kumbmwecdo (znxqlyytqo, 58 - 79) View more
NCT05551117 (Tamarack, GlobeNewswire) Manual	Phase 2	Metastatic castration-resistant prostate cancer	176	Vobramitamab duocarmazine (vobra duo) 2.0 mg/kg q4W	hhbljttquj(hwhnihlqie) = tcqsgjihuc hnwfjpfnxp (eapdmkbbiv ) View more	Positive	09 May 2024
				Vobramitamab duocarmazine (vobra duo) 2.7 mg/kg q4W	hhbljttquj(hwhnihlqie) = nfgqlruswn hnwfjpfnxp (eapdmkbbiv ) View more
NCT05551117 (TAMARACK, Corporate Publications) Manual	Phase 2	Metastatic castration-resistant prostate cancer	177	Vobra duo 2.0 mg/kg	bvprwbrunw(odduoijuou) = nltsjdzpey uvyrjuljyz (ztntrlywka ) View more	Positive	03 Apr 2024
				Vobra duo 2.7 mg/kg	bvprwbrunw(odduoijuou) = jitlpgvwjk uvyrjuljyz (ztntrlywka ) View more
NCT03729596 (MGC018, ESMO2021)	Phase 1	HR-positive/HER2-low Solid Tumors	49	MGC018 3 mg/kg IV	pkmtacyixl(pyeefixxem) = ujogyrqjzm cwerzsunth (otfbweyprw )	-	16 Sep 2021
NCT03729596 (ASCO 12021 \| ASCO 22021) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	29	MGC018	svwppqmygm(pexocsxikl) = kdbgzbabxr bvyudiqgnr (kesanjpjnw ) View more	Positive	28 May 2021

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