lorigerlimab (MGD019) / MacroGenics - LARVOL DELTA

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

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

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

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

Phase Ib/II Trial of Regorafenib Plus Lorigerlimab as Neoadjuvant Therapy for Patients With pMMR/MSS, Resectable, Lung-limited Metastatic Colorectal Cancer (clinicaltrials.gov) - P1/2 | N=30 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center

New P1/2 trial • pMMR • Colorectal Cancer • Oncology • Solid Tumor

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

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 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center

New P2 trial • Colorectal Cancer • Oncology • Solid Tumor

A Study of Lorigerlimab in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: MacroGenics | Not yet recruiting ➔ Recruiting

Enrollment open • Platinum resistant • Cervical Adenocarcinoma • Cervical Cancer • Endometrial Cancer • Fallopian Tube Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • Uterine Cancer • Vaginal Cancer • Vulvar Cancer

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

MacroGenics Provides Update on Corporate Progress and First Quarter 2025 Financial Results (Macrogenics Press Release) - "First patient dosed in LINNET Phase 2 study of lorigerlimab in ovarian and other gynecologic cancers; Clinical update on LORIKEET, a randomized 150-patient Phase 2 study of lorigerlimab in combination with docetaxel in patients with mCRPC, expected in second half of 2025...MGC026 is currently being evaluated in a Phase 1 dose escalation study in patients with advanced solid tumors, with dose expansion in selected indications expected to initiate in 2025; An Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for MGC030 is planned for 2026."

IND • P2 data • Trial status • Castration-Resistant Prostate Cancer • Ovarian Cancer

MacroGenics Provides Update on Corporate Progress and 2024 Financial Results (GlobeNewswire) - "Updates on Proprietary Investigational Programs: Lorigerlimab:...Enrollment is now complete in the ongoing LORIKEET Phase 2 trial...The Company expects to provide a clinical update in the second half of 2025. Based on MacroGenics’ cumulative experience to date from its Phase 1 and Phase 2 studies of lorigerlimab...the Company plans to conduct the LINNET Phase 2 study. This clinical trial will evaluate lorigerlimab as monotherapy in patients with either platinum-resistant ovarian cancer (PROC) or clear cell gynecologic cancer (CCGC)....The Company anticipates enrolling up to 40 patients with PROC and up to 20 patients with CCGC in LINNET, which is expected to commence by mid-2025."

P2 data • Trial status • Cervical Cancer • Endometrial Cancer • Fallopian Tube Cancer • Metastatic Castration-Resistant Prostate Cancer • Ovarian Cancer • Peritoneal Cancer • Uterine Cancer • Vaginal Cancer • Vulvar Cancer

MGD019 DART® Protein in Unresectable/Metastatic Cancer (clinicaltrials.gov) - P1 | N=162 | Completed | Sponsor: MacroGenics | Active, not recruiting ➔ Completed

Trial completion • Castration-Resistant Prostate Cancer • Colorectal Cancer • Cutaneous Melanoma • Genito-urinary Cancer • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • ALK • BRAF • MSI • ROS1

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 | Recruiting ➔ Active, not recruiting

Enrollment closed • Breast Cancer • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor • BRCA

A Study of Lorigerlimab in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: MacroGenics

Metastases • New P2 trial • Cervical Cancer • Endometrial Cancer • Fallopian Tube Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • Uterine Cancer • Vaginal Cancer • Vulvar Cancer

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) - "Emerging ADC Pipeline: MGC028:...The Company submitted an IND application for MGC028 to the U.S. Food and Drug Administration (FDA) in October; Lorigerlimab: This bispecific checkpoint molecule is being evaluated in the ongoing LORIKEET trial, a randomized Phase 2 study of lorigerlimab in combination with docetaxel vs. docetaxel alone in second-line, chemotherapy-naïve mCRPC patients....The Company anticipates completing enrollment of the study in late 2024 or early 2025 and providing a clinical update on the study in the first half of 2025."

Enrollment status • IND • P2 data • Castration-Resistant Prostate Cancer • Solid Tumor

MacroGenics Provides Update on Corporate Progress, Second Quarter 2024 Financial Results (GlobeNewswire) - "The Company anticipates completing enrollment of the study in 2024 or early 2025 and providing a clinical update in the first half of 2025....The Company continues to anticipate submitting an investigational new drug (IND) application for MGC028 by the end of 2024 and initiating a Phase 1 clinical study in 2025....MacroGenics continues to enroll patients in a Phase 1 dose-escalation study of MGD024 in patients with CD123-positive neoplasms, including acute myeloid leukemia and myelodysplastic syndromes."

Enrollment status • IND • New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Metastatic Castration-Resistant Prostate Cancer • Myelodysplastic Syndrome • Oncology • Prostate Cancer • Solid Tumor

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 Update on Corporate Progress, First Quarter 2024 Financial Results and Interim TAMARACK Phase 2 Study Data (GlobeNewswire) - "Lorigerlimab is a bispecific, tetravalent PD-1 × CTLA-4 DART molecule. In addition to the ongoing study of lorigerlimab in combination with vobra duo mentioned above, MacroGenics is enrolling LORIKEET, a randomized Phase 2 study of lorigerlimab in combination with docetaxel vs. docetaxel alone in second-line, chemotherapy-naïve mCRPC patients. A total of 150 patients are planned to be treated in the 2:1 randomized study. The current trial design includes a primary study endpoint of radiographic progression-free survival (rPFS). The Company anticipates completing enrollment of the study in 2024 and providing a clinical update in the first half of 2025."

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

A Study of MGC018 in Combination With MGD019 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=278 | Recruiting | Sponsor: MacroGenics | Trial completion date: Mar 2025 ➔ Mar 2026 | Trial primary completion date: Mar 2024 ➔ Mar 2025

Checkpoint inhibition • Combination therapy • Metastases • Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Gastrointestinal 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 and 2023 Financial Results (GlobeNewswire) - "MacroGenics intends 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."

Clinical protocol • Trial status • Anal Carcinoma • Melanoma • Metastatic Castration-Resistant Prostate Cancer • Non Small Cell Lung Cancer • Small Cell Lung Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

MacroGenics Provides Update on Corporate Progress and 2023 Financial Results (GlobeNewswire) - "MacroGenics is enrolling LORIKEET, a randomized Phase 2 study of lorigerlimab in combination with docetaxel vs. docetaxel alone in second-line, chemotherapy-naïve mCRPC patients. A total of 150 patients are planned to be treated in the 2:1 randomized study. The current trial design includes a primary study endpoint of radiographic progression-free survival (rPFS). The Company anticipates providing a study update in the second half of 2024."

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

MGD019 DART® Protein in Unresectable/Metastatic Cancer (clinicaltrials.gov) - P1 | N=162 | Active, not recruiting | Sponsor: MacroGenics | Trial completion date: Sep 2024 ➔ Dec 2024 | Trial primary completion date: Mar 2024 ➔ Jul 2024

Metastases • Trial completion date • Trial primary completion date • Colorectal Cancer • Cutaneous Melanoma • Gastrointestinal Cancer • Genito-urinary Cancer • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • ALK • BRAF • MSI • ROS1