vobramitamab duocarmazine (MGC018) / MacroGenics, Byondis - LARVOL DELTA

A Phase II Study of Vobramitamab Duocarmazine in Patients With Relapsed or Refractory Extensive-Stage Small-Cell Lung Cancer (IASLC-WCLC 2025) - P2 | "Patients received a median of 1 prior line of therapy (range 1-2); all patients received frontline platinum-etoposide chemotherapy with anti-PD-L1 immunotherapy. Conclusions : In this phase II study of vobramitamab duocarmazine in patients with relapsed/refractory ES-SCLC, limited efficacy was observed, with no objective responses leading to early termination of trial. For optimization of B7-H3 ADCs for SCLC, further work is needed to understand the ideal cytotoxic payload, dosing strategy, and biomarkers of response and resistance."

Clinical • IO biomarker • P2 data • Anemia • Anorexia • Conjunctivitis • Fatigue • Infectious Disease • Lung Cancer • Mucositis • Neutropenia • Ocular Infections • Ocular Inflammation • Oncology • Ophthalmology • Pneumonia • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor • Stomatitis • Thrombocytopenia

Recent advances in antibody-drug conjugates for metastatic castration-resistant prostate cancer. (PubMed, Zhejiang Da Xue Xue Bao Yi Xue Ban) - P3 | "Among prostate-specific membrane antigen (PSMA)-targeted ADCs, ARX517 demonstrates superior safety and more significant prostate-specific antigen (PSA) reductions compared to earlier agents such as MLN2704, PSMA-ADC, and MEDI3726. ADCs targeting B7-H3, such as MGC018 and DB-1311, have also shown antitumor activity. ADCs targeting other antigens, including six-transmembrane epithelial antigen of the prostate (STEAP)1 (DSTP3086S), trophoblast cell surface antigen (TROP)2 (sacituzumab govitecan), and solute carrier (SLC) 44A4 (ASG-5ME), have shown preliminary antitumor activity in early trials but face challenges with insufficient efficacy or toxicity. Tisotumab vedotin (targeting tissue factor) has shown no significant therapeutic response in mCRPC. Meanwhile, disitamab vedotin (HER2-targeted), ABBV-969 (dual PSMA/STEAP1-targeted), and DXC008 (dual PSMA/STEAP1-targeted) are currently under evaluation. Notably, the B7-H3-targeted ADC ifinatamab deruxtecan has initiated..."

Journal • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • HER-2 • SLC44A4 • SLC4A4 • STEAP1

CP-MGC018-02: A Study of MGC018 in Combination With MGD019 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=32 | Active, not recruiting | Sponsor: MacroGenics | N=278 ➔ 32

Checkpoint inhibition • Enrollment change • Castration-Resistant Prostate Cancer • Epithelial Ovarian Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Liver Cancer • Melanoma • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor

MGC018-SCLC: MGC018 in Patients With Relapsed or Refractory Extensive-Stage Small-Cell Lung Cancer (clinicaltrials.gov) - P2 | N=9 | Active, not recruiting | Sponsor: Georgetown University | N=17 ➔ 9 | Recruiting ➔ Active, not recruiting

Enrollment change • Enrollment closed • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

CP-MGC018-02: A Study of MGC018 in Combination With MGD019 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=278 | Active, not recruiting | Sponsor: MacroGenics | Trial completion date: Jun 2025 ➔ Oct 2025 | Trial primary completion date: Apr 2025 ➔ Jul 2025

Checkpoint inhibition • Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Epithelial Ovarian Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Liver Cancer • Melanoma • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor

The B7-H3 targeting antibody-drug conjugate (ADC) vobramitamab duocarmazine (vobra duo) is potently effective against a broad panel of pediatric solid tumor xenograft models: A study from the Pediatric Preclinical In Vivo Testing (PIVOT) Consortium (AACR 2025) - P1/2 | "Vobra duo is potently efficacious across a broad panel of pediatric solid tumor xenograft models supporting clinical development of this agent and other agents targeting B7-H3 for children with cancer."

Preclinical • Castration-Resistant Prostate Cancer • CNS Tumor • Ewing Sarcoma • Genito-urinary Cancer • Hematological Malignancies • Hepatoblastoma • Neuroblastoma • Oncology • Osteosarcoma • Prostate Cancer • Rhabdoid Tumor • Rhabdomyosarcoma • Sarcoma • Solid Tumor • Wilms Tumor

Preclinical characterization of the anti-tumor activity of the investigational anti-B7-H3 antibody-drug conjugate (ADC), vobramitamab duocarmazine (vobra duo), in pediatric sarcomas (pSC) (AACR 2025) - "Vobra duo shows anti-tumor activity toward in vitro and in vivo models of pSC. Further in depth pre-clinical assessment to support potential clinical application is warranted."

Preclinical • CNS Tumor • Neuroblastoma • Oncology • Osteosarcoma • Rhabdomyosarcoma • Sarcoma • Solid Tumor • ANXA5 • CASP3 • CD276 • LAMP1 • MAP1LC3A

Update on Vobramitamab Duocarmazine (GlobeNewswire) - P2 | N=192 | TAMARACK (NCT05551117) | Sponsor: MacroGenics | "Results for the concluded TAMARACK Phase 2 study included, based on a February 21, 2025 data cut-off, mature median radiographic progression-free survival (rPFS) of 9.5 months for the 2.0 mg/kg cohort (95% CI, 8.5-11.2) and 10.0 months for the 2.7 mg/kg cohort (95% CI, 7.4-11.4) in patients with mCRPC. Safety data from the study remained consistent with prior data disclosures. 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."

P2 data • Pipeline update • Castration-Resistant Prostate Cancer

Tamarack: A Study of Vobramitamab Duocarmazine in Participants With Metastatic Castration Resistant Prostate Cancer and Other Solid Tumors (clinicaltrials.gov) - P2 | N=192 | Completed | Sponsor: MacroGenics | Active, not recruiting ➔ Completed

Trial completion • Anal Carcinoma • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Head and Neck Cancer • Laryngeal Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Oral Cancer • Prostate Adenocarcinoma • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

CP-MGC018-02: A Study of MGC018 in Combination With MGD019 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=278 | Active, not recruiting | Sponsor: MacroGenics | Recruiting ➔ Active, not recruiting | Trial completion date: Mar 2026 ➔ Jun 2025

Checkpoint inhibition • Combination therapy • Enrollment closed • Metastases • Trial completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Melanoma • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor

MacroGenics Provides Update on Corporate Progress, Third Quarter 2024 Financial Results (GlobeNewswire) - "Updates on Proprietary Investigational Programs:...The TAMARACK Phase 2 study of vobra duo is being conducted in patients with metastatic castration-resistant prostate cancer (mCRPC). While study participants are no longer being dosed in the study, participants continue to be monitored for adverse events, disease progression and survival. The Company...expects to have mature median radiographic progression-free survival (rPFS) data in hand no later than early 2025....Until MacroGenics completes its assessment of the monotherapy development opportunity for vobra duo in mCRPC, the Company has paused its other development efforts in alternative tumor types as well as the Phase 1/2 dose combination study of vobra duo plus lorigerlimab."

P2 data • Pipeline update • Trial status • Castration-Resistant Prostate Cancer

Tamarack: A Study of Vobramitamab Duocarmazine in Participants With Metastatic Castration Resistant Prostate Cancer and Other Solid Tumors (clinicaltrials.gov) - P2 | N=192 | Active, not recruiting | Sponsor: MacroGenics | Trial primary completion date: Feb 2025 ➔ Jul 2024

Metastases • Trial primary completion date • Anal Carcinoma • Castration-Resistant Prostate Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Laryngeal Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Oral Cancer • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Tamarack: A Study of Vobramitamab Duocarmazine in Participants With Metastatic Castration Resistant Prostate Cancer and Other Solid Tumors (clinicaltrials.gov) - P2 | N=192 | Active, not recruiting | Sponsor: MacroGenics | N=382 ➔ 192 | Trial completion date: May 2027 ➔ Feb 2025 | Trial primary completion date: May 2027 ➔ Feb 2025

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Anal Carcinoma • Castration-Resistant Prostate Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Laryngeal Cancer • Lung Cancer • Melanoma • Metastatic Castration-Resistant Prostate Cancer • Non Small Cell Lung Cancer • Oncology • Oral Cancer • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

TAMARACK: Randomized Phase II trial of the B7-H3 targeting antibody drug conjugate (ADC) vobramitamab duocarmazine (vobra duo) in metastatic castration-resistant prostate cancer (mCRPC) (ESMO 2024) - P1/2, P2 | "Phase 1 testing (NCT03729596) of vobra duo demonstrated anti-tumor activity in mCRPC, with adverse events at 3.0 mg/kg Q3W resulting in frequent early treatment discontinuation. TAMARACK (NCT05551117) is a randomized, open-label, Phase 2 dose selection study assessing efficacy and tolerability of two dose levels of vobra duo (2.0 mg/kg and 2.7 mg/kg IV Q4W) in pts with mCRPC previously treated with abiraterone, enzalutamide, or apalutamide; prior docetaxel was allowed. Vobra duo had acceptable tolerability and anti-tumor activity in mCRPC meriting further evaluation in later phase trials."

Clinical • Metastases • P2 data • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Vobramitamab duocarmazine: "Vobra duo yields antitumor activity in mCRPC as demonstrated by ORR, PSA response rate, and 6-month rPFS rate“; Prostate cancer (Macrogenics) - ESMO 2024: "Treatment with 2.7 mg/kg Q4W yielded a higher ORR than 2.0 mg/kg Q4W; with PSA responses similar between the two arms"

P2 data • Genito-urinary Cancer • Oncology • Prostate Cancer

MacroGenics Announces Updated Efficacy & Safety Data from TAMARACK Phase 2 Study of Vobra Duo in mCRPC Patients at ESMO Congress 2024 (GlobeNewswire) - P2 | N=382 | Tamarack (NCT05551117) | Sponsor: MacroGenics | "Ultimately, our path forward for the molecule will depend on the final safety and efficacy data, including mature median rPFS, which we expect to have in hand no later than early 2025...In the intent-to-treat (ITT) population, 6-month rPFS rate was 69% for the 2.0 mg/kg arm (95% CI, 57-79) and 70% for the 2.7 mg/kg arm (95% CI, 58-79)...Although immature, with only 65 PFS events (35.9%) as of the data cut-off, median rPFS was approximately 8.5 months for the 2.0 mg/kg cohort (95% CI, 7.2-11.2) and 7.5 months for the 2.7 mg/kg cohort (95% CI, 7.2-10.6)...Out of 45 RECIST-response evaluable patients in the 2.0 mg/kg arm, the confirmed objective response rate (ORR) was 20.0% (n=9) and the unconfirmed ORR was 26.7% (n=12). Out of 32 RECIST-response evaluable patients in the 2.7 mg/kg arm, the confirmed ORR was 40.6% (n=13) and the unconfirmed ORR was 46.9% (n=15)."

P2 data • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Solid Tumor

MacroGenics Announces TAMARACK Phase 2 Data Presentation at ESMO Congress 2024 (GlobeNewswire) - "MacroGenics...announced a poster presentation relating to Phase 2 data of vobramitamab duocarmazine in metastatic castration-resistant prostate cancer (mCRPC) at the European Society for Medical Oncology (ESMO) Congress....The abstract submitted to ESMO in May 2024, now available on the ESMO website, was based on a data cut-off from April 12, 2024, and the poster will report data from a July 9, 2024, data cut-off. Data to be presented at ESMO will include updated safety and efficacy data, including the study’s primary endpoint of landmark 6-month radiographic progression-free survival (rPFS), as well as immature median rPFS that may change as additional PFS events accrue."

P2 data • Metastatic Castration-Resistant Prostate Cancer

MacroGenics Provides Update on Corporate Progress, Second Quarter 2024 Financial Results (GlobeNewswire) - "Updated TAMARACK safety and efficacy data, including the study’s primary endpoint, will be presented in a poster session at the ESMO Congress in September 2024. This data will be based on a data cut-off date of July 9, 2024. The abstract submitted to ESMO in May was based on an April 12 data cut off. MacroGenics expects to have the mature efficacy findings, including median rPFS, in the second half of 2024 and plans to present the data at a subsequent medical conference....MacroGenics continues to enroll a Phase 1/2 dose escalation study of vobra duo in combination with lorigerlimab in patients with various advanced solid tumors. The Company anticipates commencing a dose expansion study of this combination later this year."

Enrollment status • New trial • P2 data • Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

MacroGenics Provides Vobramitamab Duocarmazine Update (GlobeNewswire) - "MacroGenics...announced a poster (display) presentation of clinical data from the TAMARACK Phase 2 study of vobramitamab duocarmazine (vobra duo) at the upcoming...ESMO Congress 2024....The abstract submitted to ESMO was based on an April 12 data cut off, and the poster will report additional data from a July 9 data cut-off, including safety, efficacy and landmark 6-month radiographic progression-free survival (rPFS) data....In late July 2024, after a review of accumulated study data, MacroGenics agreed with the study’s...IDMC recommendation that study treatment should be discontinued for the remaining mCRPC study participants who potentially could have received additional doses. Most of these remaining study participants had already received 8-12 cycles of vobra duo....The Company expects to have the mature efficacy findings, including median rPFS, later in the second half of 2024 and plans to present the data at a subsequent medical conference."

DSMB • P2 data • Trial status • Metastatic Castration-Resistant Prostate Cancer

A Phase II Study of Vobramitamab Duocarmazine in Patients with Relapsed or Refractory Extensive-Stage Small Cell Lung Cancer (IASLC-WCLC 2024) - No abstract available

Clinical • P2 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Vobramitamab duocarmazine: "Confirmed Objective Response Rate (ORR) (CR+PR), n (%) (95% CI): Vobra Duo 2.0 mg/kg q4W: 8 (17.8%); Vobra Duo 2.7 mg/kg q4W: 8 (25.0%)"; Prostate cancer (Macrogenics) - TAMARACK Phase 2 Interim Data

P2 data • Genito-urinary Cancer • Oncology • Prostate Cancer

MacroGenics Provides Update on Corporate Progress, First Quarter 2024 Financial Results and Interim TAMARACK Phase 2 Study Data (GlobeNewswire) - "MacroGenics plans to expand the TAMARACK study of vobra duo by enrolling patients with non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), melanoma, squamous cell carcinoma of the head and neck (SCCHN) and anal cancer. The Company expects to initiate dosing in these additional cohorts in mid-2024. MacroGenics continues to enroll a Phase 1/2 dose escalation study of vobra duo in combination with lorigerlimab in patients with various advanced solid tumors. The Company anticipates commencing a dose expansion study of this combination in mCRPC and at least one additional indication in 2024."

Trial status • Hepatocellular Cancer • Melanoma • Metastatic Castration-Resistant Prostate Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Ductal Adenocarcinoma • Renal Cell Carcinoma • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

MacroGenics Provides Update on Corporate Progress, First Quarter 2024 Financial Results and Interim TAMARACK Phase 2 Study Data (GlobeNewswire) - P2 | N=382 | Tamarack (NCT05551117) | Sponsor: MacroGenics | "The median number of cycles of vobra duo administered was five (range of 1-10). A total of five events with fatal outcome occurred as follows: one Grade 5 event in the 2.0 mg/kg dosing cohort: acute myocardial infarction (considered unrelated to study drug by the investigator); three Grade 5 events in the 2.7 mg/kg dosing cohort: one cardiac arrest (considered unrelated to study drug by the investigator) and two events of pneumonitis....Based on a current evaluation of this interim data, the Company is undertaking the initial steps necessary to prepare for the potential initiation of a Phase 3 study in mCRPC in 2025....The Company intends to share final safety, efficacy, and durability data, including the primary endpoint of radiographic progression-free survival, from the TAMARACK trial in the second half of 2024."

New P3 trial • P2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Preclinical development of MGC026, a glycan-linked, exatecan-based antibody-drug conjugate (ADC) targeting B7-H3 for solid cancer (AACR 2024) - "A duocarmycin-based B7-H3-targeted DNA-alkylating ADC, vobramitamab duocarmazine (vobra duo), has shown encouraging clinical activity in the treatment of metastatic castration-resistant prostate cancer. MGC026 exhibited a favorable preclinical profile, with potent in vivo activity toward B7-H3-expressing tumor xenografts representing a range of cancer indications. MGC026 was tolerated in cynomolgus monkeys, a relevant toxicology model, at exposure levels exceeding those required for antitumor activity. These data support clinical development of MGC026 for the treatment of B7-H3-expressing solid cancers."

Preclinical • Genito-urinary Cancer • Head and Neck Cancer • Melanoma • Metastatic Castration-Resistant Prostate Cancer • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

MGC018-SCLC: MGC018 in Patients With Relapsed or Refractory Extensive-Stage Small-Cell Lung Cancer (clinicaltrials.gov) - P2 | N=17 | Recruiting | Sponsor: Georgetown University | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor