lorigerlimab (MGD019) / MacroGenics - LARVOL DELTA

Triage of advanced cervical cancer through immunotherapy induction (TRACTION). (ASCO 2024) - P2 | "CheckMate-358 utilized two dosing regimens of ipilimumab and nivolumab in advanced/recurrent cervical cancer...Given the potential benefit of CTLA-4/PD-1 blockade in the upfront setting, we propose a phase II trial examining the strategy of induction immunotherapy with lorigerlimab (bispecific antibody targeting CTLA-4 and PD-1) in chemo-naïve cervical cancer patients not amenable to curative treatment...At any time point, all patients at first disease progression will subsequently receive physician's choice standard of care systemic therapy with carboplatin/paclitaxel +/- pembrolizumab +/- bevacizumab and will be followed for survival...Key eligibility criteria include 1) recurrent, metastatic, or persistent cervical cancer 2) squamous cell carcinoma, adenosquamous, or adenocarcinoma histologic subtype 3) not amenable to curative surgery or radiation. The trial is open with 14 of planned 40 patients enrolled at the time of submission."

Metastases • Cervical Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • PD-L1

Checkmate: A Case of Severe Refractory Immune Checkpoint Inhibitor Hepatitis (ACG 2026) - "Case Description/ A 54-year-old female with stage IC1 clear cell ovarian cancer with liver metastases was treated with lorigerlimab, a bispecific CTLA-4/PD-1 inhibitor, two months prior to presenting with elevated liver enzymes...She received methylprednisolone 100 mg daily for 3 days followed by outpatient prednisone taper for presumed ICI hepatitis...She was then started on IV methylprednisolone 60 mg twice daily and mycophenolate mofetil (MMF) 500 mg twice daily. Ursodiol was added for ductopenia...Figure: Figure 1. Liver Biopsy, hematoxylin and eosin stain, 400x magnification (A) Endothelialitis is shown with neutrophils and lymphocytes undermining and displacing the endothelial cells; (B) Zone 3 is present with lymphohistiocytic inflammation and mild sinusoidal dilation with congestion; (C) this portal tract lacks a primary bile duct concerning for bile duct loss, (D) Bile duct injury is shown characterized by vacuolization of the biliary epithelium with a few..."

Checkpoint inhibition • Clinical • Gastrointestinal Disorder • Hepatology • Inflammation • Liver Failure • Oncology • Ovarian Cancer • Ovarian Clear Cell Cancer • Solid Tumor

Lorigerlimab, a bispecific PD-1×CTLA-4 DART molecule in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): A phase 1 expansion (exp) cohort. (ASCO-GU 2023) - P1 | "Lorigerlimab demonstrates a manageable safety profile with evidence of encouraging and durable antitumor activity in a chemotherapy refractory mCRPC population. Randomized evaluation of lorigerlimab in mCRPC is warranted. Clinical trial information: NCT03761017."

Clinical • IO biomarker • Metastases • P1 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CTLA4 • ICOS • PD-1

LINNET: A phase 2 study to evaluate lorigerlimab in participants (pts) with advanced gynecologic cancers (ESMO 2026) - No abstract available

Clinical • Metastases • P2 data • Gynecologic Cancers • Oncology

Triage of Advanced Cervical Cancer Through Immunotherapy Induction (TRACTION) (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Suspended ➔ Recruiting

Enrollment open • Cervical Cancer • Oncology • Solid Tumor

Regorafenib (Reg) and Lorigerlimab (Lor), RELO Regimen, in Treatment of High-risk Patients With Colorectal Cancer With Radiographic Occult Molecular Residual Disease After End of Established Definitive Therapy [ReLOAD Trial] (clinicaltrials.gov) - P2 | N=16 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Suspended ➔ Recruiting

Enrollment open • Colorectal Cancer • Oncology • Solid Tumor

Lorigerlimab: Enrollment completion of CCGC cohort of P2 trial (NCT06730347) for solid tumors by year-end 2026 (Macrogenics) - Corporate Presentation: Updated data from P2 trial (NCT06730347) for solid tumors in H1 2027

Enrollment status • P2 data • Gynecologic Cancers • Oncology • Solid Tumor

The Company also plans to present the…poster on lorigerlimab, an investigational, bispecific DART molecule that targets PD-1 and CTLA-4…at the European Society for Medical Oncology (ESMO) 2026 Congress (GlobeNewswire) - "Title: LINNET: A phase 2 study to evaluate lorigerlimab in participants (pts) with advanced gynecologic cancers; Presentation Number: 1278P; Lead Author: Amir Jazaeri, M.D.; Date: Monday, October 26, 2026."

P2 data • Platinum resistant • Cervical Cancer • Endometrial Cancer • Fallopian Tube Cancer • Ovarian Cancer • Peritoneal Cancer • Uterine Cancer • Vaginal Cancer

Triage of Advanced Cervical Cancer Through Immunotherapy Induction (TRACTION) (clinicaltrials.gov) - P2 | N=47 | Suspended | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Jun 2026 ➔ Jun 2028 | Trial primary completion date: Jun 2026 ➔ Jun 2028

Trial completion date • Trial primary completion date • Cervical Cancer • Oncology • Solid Tumor

A Study of Lorigerlimab in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P2 | N=80 | Recruiting | Sponsor: MacroGenics | N=60 ➔ 80 | Trial completion date: Aug 2027 ➔ Dec 2027 | Trial primary completion date: Feb 2027 ➔ Jul 2027

Enrollment change • Platinum resistant • Trial completion date • Trial primary completion date • Breast Cancer • Cervical Adenocarcinoma • Cervical Cancer • Endometrial Cancer • Fallopian Tube Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • Uterine Cancer • Vaginal Cancer • Vulvar Cancer • BRCA

Triage of Advanced Cervical Cancer Through Immunotherapy Induction (TRACTION) (clinicaltrials.gov) - P2 | N=47 | Suspended | Sponsor: M.D. Anderson Cancer Center | Recruiting ➔ Suspended

Trial suspension • Cervical Cancer • Oncology • Solid Tumor

Lorigerlimab (MGD019) in Patients With Pancreatic Adenocarcinoma and Homologous Recombination Deficiency (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: Peter Hosein, MD

New P2 trial • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • BRCA1 • BRCA2 • RAD51C • RAD51D

A phase 2 multicohort study to evaluate lorigerlimab (PD-1 x CTLA-4) in participants with advanced solid tumors (AACR 2026) - P2 | "Participants with PROC must have received at least one and up to three prior lines of systemic therapy, which may include prior bevacizumab. Tumor assessments occur every 9 weeks for the first 54 weeks, then every 12 weeks until treatment discontinuation. Enrollment commenced in May 2025 and is ongoing."

IO biomarker • Metastases • P2 data • Cervical Cancer • Gynecologic Cancers • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA • CTLA4 • PD-1

LORIKEET: A Study of Lorigerlimab With Docetaxel or Docetaxel Alone in Participants With Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P2 | N=154 | Completed | Sponsor: MacroGenics | Active, not recruiting ➔ Completed

Trial completion • Breast Cancer • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor • BRCA

FDA Removes Partial Clinical Hold on MacroGenics’ LINNET Study (Macrogenics Press Release) - "Plan to resume enrollment in clinical study of lorigerlimab in gynecologic cancers; On track to provide mid-2026 program update...During the partial clinical hold, previously enrolled study participants were allowed to continue to receive study drug. Going forward, new participants will be enrolled under a revised protocol that includes additional risk-mitigation measures for potential hematologic and cardiac toxicities....To date, 41 study participants have been dosed in the LINNET study..."

Enrollment status • FDA event • P2 data • Platinum resistant • Cervical Cancer • Endometrial Cancer • Fallopian Tube Cancer • Ovarian Cancer • Peritoneal Cancer • Uterine Cancer • Vaginal Cancer • Vulvar Cancer

LORIKEET: A Study of Lorigerlimab With Docetaxel or Docetaxel Alone in Participants With Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P2 | N=154 | Active, not recruiting | Sponsor: MacroGenics | Trial completion date: Sep 2027 ➔ Mar 2026 | Trial primary completion date: Sep 2026 ➔ Feb 2026

Trial completion date • Trial primary completion date • Breast Cancer • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor • BRCA

Anticipated Milestones:…Lorigerlimab (GlobeNewswire) - "The LINNET study is a Phase 2 monotherapy trial evaluating lorigerlimab, a PD-1 × CTLA-4 bispecific DART molecule, in patients with either platinum-resistant ovarian cancer (PROC) or clear cell gynecologic cancer (CCGC)....MacroGenics continues to plan for a clinical update in mid-2026."

P2 data • Platinum resistant • Ovarian Cancer

MacroGenics…announced that the U. S. Food and Drug Administration (FDA) has placed a partial clinical hold on its Phase 2 LINNET study of lorigerlimab, an investigational, bispecific DART molecule that targets PD-1 and CTLA-4, in patients with gynecologic cancers (GlobeNewswire) - "Under the partial clinical hold, no new patients will be enrolled in the LINNET study until the partial hold is lifted by the FDA. Current study participants may continue to receive study drug. The FDA’s partial clinical hold was initiated following the Company’s recent notification to the FDA of a temporary pause in enrollment of new participants in the LINNET trial due to the occurrence of recent safety events."

Enrollment status • FDA event • Platinum resistant • Cervical Cancer • Endometrial Cancer • Fallopian Tube Cancer • Ovarian Cancer • Peritoneal Cancer • Uterine Cancer • Vaginal Cancer • Vulvar Cancer

Regorafenib (Reg) and Lorigerlimab (Lor), RELO Regimen, in Treatment of High-risk Patients With Colorectal Cancer With Radiographic Occult Molecular Residual Disease After End of Established Definitive Therapy [ReLOAD Trial] (clinicaltrials.gov) - P2 | N=16 | Suspended | Sponsor: M.D. Anderson Cancer Center | Not yet recruiting ➔ Suspended

Trial suspension • Colorectal Cancer • Oncology • Solid Tumor

A Trial of Regorafenib Plus Lorigerlimab as Neoadjuvant Therapy for Patients With pMMR/MSS, Resectable, Lung-limited Metastatic Colorectal Cancer (clinicaltrials.gov) - P1/2 | N=0 | Withdrawn | Sponsor: M.D. Anderson Cancer Center | N=30 ➔ 0 | Trial completion date: Dec 2032 ➔ Jan 2026 | Initiation date: Feb 2026 ➔ Sep 2025 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Dec 2030 ➔ Jan 2026

Enrollment change • pMMR • Trial completion date • Trial initiation date • Trial primary completion date • Trial withdrawal • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Lung Cancer • Oncology • Rectal Adenocarcinoma • Solid Tumor • MLH1 • MSH2 • MSH6 • MSI

A Trial of Regorafenib Plus Lorigerlimab in Patients With Locally Recurrent or Regrowing pMMR/MSS Localized Rectal Cancer (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: M.D. Anderson Cancer Center | N=20 ➔ 0 | Trial completion date: Sep 2032 ➔ Jan 2026 | Initiation date: Apr 2026 ➔ Oct 2025 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Sep 2030 ➔ Jan 2026

Enrollment change • pMMR • Trial completion date • Trial initiation date • Trial primary completion date • Trial withdrawal • Colorectal Cancer • Oncology • Rectal Adenocarcinoma • Rectal Cancer • Solid Tumor • MLH1 • MSH2 • MSH6 • MSI

Bispecific Dual-Immune Checkpoint Inhibitor Associated Cutaneous Toxicity: A Report of Lorigerlimab Adverse Skin Reaction in Two Cancer Patients. (PubMed, J Cutan Pathol) - "The eruption was refractory to treatment, despite the patient withholding lorigerlimab, leading to complete discontinuation of lorigerlimab. This report highlights the importance of histopathologic evaluation in guiding treatment decisions for lorigerlimab-associated irAEs and underscores the need for further research into its dermatologic irAEs."

Adverse events • Checkpoint inhibition • Journal • Atopic Dermatitis • Castration-Resistant Prostate Cancer • Dermatitis • Dermatology • Genito-urinary Cancer • Immunology • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Pruritus • Solid Tumor • CTLA4 • PD-1

Phase II Trial of Regorafenib Plus Lorigerlimab in Patients With Locally Recurrent or Regrowing pMMR/MSS Localized Rectal Cancer (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center

New P2 trial • pMMR • Colorectal Cancer • Oncology • Rectal Cancer • Solid Tumor

CP-MGC018-02: A Study of MGC018 in Combination With MGD019 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=31 | Completed | Sponsor: MacroGenics | Active, not recruiting ➔ Completed

Checkpoint inhibition • Trial completion • 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

Key Strategic Priorities for 2025 and 2026 (Macrogenics Press Release) - "Determine development path for lorigerlimab based on data from the ongoing LORIKEET and LINNET studies. Advance MGC026 and MGC028 programs to assess clinical proof-of-concept. Submit Investigational New Drug (IND) application for MGC030. Initiate IND-enabling studies for two new product candidates. Forge partnerships and collaborations to accelerate development of the Company’s proprietary product candidates and technology platforms."

IND • M&A • Preclinical • Oncology