PF-08046045 / Pfizer - LARVOL DELTA

Open-Label Phase 1 Study to Evaluate the Safety of SGN-35T in Patients with Relapsed/Refractory CD30-Expressing Lymphoid Malignancies (SGN35T-001; trial in progress) (ASH 2024) - P1 | "Brentuximab vedotin (BV), a CD30-directed antibody-drug conjugate (ADC), has demonstrated clinical benefit in classic Hodgkin lymphoma and peripheral T-cell lymphomas.SGN-35T is an investigational ADC comprised of an anti-CD30 monoclonal antibody, conjugated to monomethyl auristatin E (MMAE) via a novel protease-cleavable tripeptide linker with a drug-to-antibody ratio of approximately four. Secondary endpoints include PK parameters, objective response rate, duration of response, and complete response rate. Enrollment is ongoing in the US and Spain but planned globally."

Clinical • P1 data • Acute Graft versus Host Disease • B Cell Lymphoma • Chronic Graft versus Host Disease • Classical Hodgkin Lymphoma • Cytomegalovirus Infection • Graft versus Host Disease • Hematological Malignancies • Hodgkin Lymphoma • Immunology • Infectious Disease • Interstitial Lung Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • Pulmonary Disease • Respiratory Diseases • T Cell Non-Hodgkin Lymphoma • TNFRSF8

A Safety Study of PF-08046045/SGN-35T in Adults With Advanced Cancers (clinicaltrials.gov) - P1 | N=22 | Active, not recruiting | Sponsor: Seagen, a wholly owned subsidiary of Pfizer | Recruiting ➔ Active, not recruiting | N=150 ➔ 22 | Trial completion date: Jun 2029 ➔ Jan 2026 | Trial primary completion date: Jun 2028 ➔ Jan 2026

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • B Cell Lymphoma • Classical Hodgkin Lymphoma • Cutaneous T-cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • ALK • TNFRSF8

A Safety Study of PF-08046045/SGN-35T in Adults With Advanced Cancers (clinicaltrials.gov) - P1 | N=150 | Recruiting | Sponsor: Seagen, a wholly owned subsidiary of Pfizer | Trial completion date: Apr 2030 ➔ Jun 2029 | Trial primary completion date: Jun 2027 ➔ Jun 2028

Trial completion date • Trial primary completion date • B Cell Lymphoma • Classical Hodgkin Lymphoma • Cutaneous T-cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • ALK • TNFRSF8

A Safety Study of PF-08046045/SGN-35T in Adults With Advanced Cancers (clinicaltrials.gov) - P1 | N=150 | Recruiting | Sponsor: Seagen, a wholly owned subsidiary of Pfizer | N=110 ➔ 150

Enrollment change • B Cell Lymphoma • Classical Hodgkin Lymphoma • Cutaneous T-cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • ALK • TNFRSF8

A Safety Study of SGN-35T in Adults With Advanced Cancers (clinicaltrials.gov) - P1 | N=110 | Recruiting | Sponsor: Seagen, a wholly owned subsidiary of Pfizer | Active, not recruiting ➔ Recruiting | N=18 ➔ 110

Enrollment change • Enrollment open • B Cell Lymphoma • Classical Hodgkin Lymphoma • Cutaneous T-cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • ALK • TNFRSF8

A Safety Study of SGN-35T in Adults With Advanced Cancers (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: Seagen Inc. | Recruiting ➔ Active, not recruiting | N=110 ➔ 18

Enrollment change • Enrollment closed • Metastases • B Cell Lymphoma • Cutaneous T-cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • ALK • TNFRSF8

OPEN-LABEL PHASE 1 STUDY TO EVALUATE THE SAFETY OF SGN-35T IN PATIENTS WITH RELAPSED/REFRACTORY CD30-EXPRESSING LYMPHOID MALIGNANCIES (SGN35T-001; TRIAL IN PROGRESS) (ISHL 2024) - P1 | "Brentuximab vedotin (BV), a CD30-directed antibody-drug conjugate (ADC), has demonstrated clinical benefit in cHL and PTCL.SGN-35T is an investigational ADC comprised of an anti-CD30 monoclonal antibody, conjugated to monomethyl auristatin E (MMAE) via a novel protease-cleavable tripeptide linker with a drug-to-antibody ratio of approximately 4. Secondary endpoints include PK parameters, objective response rate, duration of response, and complete response rate. Enrollment is ongoing in the US and planned globally."

Clinical • P1 data • Hematological Malignancies • Lymphoma • Oncology • TNFRSF8

Discovery of A Novel Auristatin Antibody Drug Conjugate Drug Linker With Equal Efficacy & Reduced Bone Marrow Toxicity Compared to Vedotin (ADC London 2024) - "Celebrating enhanced safety: bone marrow-friendly dLAE drug linker allows higher doses with reduced toxicity • Spotlighting improved efficacy: Comparable efficacy to vedotin ADCs in mouse models, promising results in NHP studies. • Laying out clinical progress: initiating Phase 1 trial for SGN-35T in lymphoid malignancies starting Q4 2023"

Clinical • Hematological Malignancies • Oncology

A Safety Study of SGN-35T in Adults With Advanced Cancers (clinicaltrials.gov) - P1 | N=110 | Recruiting | Sponsor: Seagen Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Cutaneous T-cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • ALK • TNFRSF8

Activated regulatory T cells in solid tumors express CD30, which are selectively targeted by the novel anti-CD30 antibody drug conjugate SGN-35T (SITC 2023) - P2 | "The anti-CD30 antibody-drug conjugate (ADC) brentuximab vedotin is approved for the treatment of advanced classical Hodgkin lymphoma and other CD30-expressing lymphomas. It is currently being tested in combination with pembrolizumab for the ability to deplete Tregs and increase immune checkpoint activity in anti-PD-1-refractory metastatic melanoma and NSCLC (NCT04609566)...Conclusions Thus, the cytotoxic activity of SGN-35T on CD30-expressing Tregs is likely a combination of the enrichment of CD30 expression on activated Tregs coupled with reduced drug efflux capacity. Together, these data support future clinical investigation of SGN-35T in combination with anti-PD-1/PD-L1 checkpoint inhibitors in solid tumors."

IO biomarker • Hematological Malignancies • Hodgkin Lymphoma • Lung Cancer • Lymphoma • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD8

Seagen Third Quarter 2023 Financial Results Reflect Strong Product Sales Growth, and Significant Portfolio and Pipeline Progress (Seagen Press Release) - "The Company expects to initiate a phase 3 trial for SGN-B6A, a novel, vedotin ADC targeting integrin beta-6, as a monotherapy in previously treated patients with NSCLC before the end of 2023....The Company initiated a phase 1 trial for SGN-EGFRd2, a gamma delta bispecific T-cell engager for EGFR-expressing solid tumors. Year to date, the Company has submitted INDs for three novel targeted cancer therapies, including SGN-EGFRd2, SGN-35T and SGN-CEACAM5C, with the goal of submitting one additional IND before year end."

IND • Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Seagen Highlights First Solid Tumor Data for an ADCETRIS (brentuximab vedotin) Immunotherapy Combination and Preclinical Data for Novel CD30-Directed Antibody-Drug Conjugate at Society for Immunotherapy of Cancer (SITC) Annual Meeting (Seagen Press Release) - "Preclinical data suggest that SGN-35T may be highly effective, like ADCETRIS, with the potential for improved tolerability. SGN-35T is an investigational agent, and its safety and efficacy have not been established...In this in vitro study, SGN-35T was cytotoxic to CD30-expressing tumor cells and CD30-expressing regulatory T cells, whereas CD8-expressing T cells were unaffected by SGN-35T. The observations support future clinical investigation of SGN-35T in solid tumors."

Preclinical • Oncology • Solid Tumor

A Safety Study of SGN-35T in Adults With Advanced Cancers (clinicaltrials.gov) - P1 | N=110 | Not yet recruiting | Sponsor: Seagen Inc.

Metastases • New P1 trial • Cutaneous T-cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • ALK • TNFRSF8