camidanlumab tesirine (ADCT-301) / Genmab, ADC Therapeutics - LARVOL DELTA

MODULE 6: Current and Future Management of R/R HL (ASH 2023) - "Supported by educational grants from AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb, Genentech, a member of the Roche Group, Genmab US Inc, Merck and Seagen Inc. Potential role of BV alone or in combination with chemotherapy or immune checkpoint inhibition as a bridge to transplant Key efficacy and safety findings from the Phase III KEYNOTE-204 trial evaluating pembrolizumab versus BV for R/R HL; implications for clinical practice Published data with and ongoing evaluation of anti-PD-1/PD-L1 antibodies in combination with other systemic approaches for R/R HL, such as BV or chemotherapy Mechanism of action and structural components of the novel antibody-drug conjugate camidanlumab tesirine Principal efficacy and safety findings from the pivotal Phase II study of camidanlumab tesirine for patients with heavily pretreated HL; potential role in practice Other promising agents/strategies for patients with HL (eg, investigational immune checkpoint inhibitors, CAR T-cell..."

Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Mantle Cell Lymphoma • Oncology

OX40-ADC, a potential new class of cancer immunotherapy by depleting Treg within TME (SITC 2025) - "One attempt by CD25-ADC (ADCT-301) failed for severe toxicities. A new CD25-ADC (PF-08046032) with attenuated affinity to CD25 and a less toxic VC-MMAE demonstrated preferential killings of TIL-Treg over peripheral Treg or CD8+ T cells, expecting widened therapeutic window...We plan to present the preliminary data of these studies during the meeting.Conclusions OX40-ADC can potentially deplete TIL-Treg to enhance tumor immunity/anti-tumor activities in animal models. HX111 could be such a candidate drug for tumor treatment, with enhanced efficacy when combined with PD-1 blockades."

Oncology • CCR8 • CD4 • CD8 • IL2RA

Camidanlumab Tesirine for Relapsed or Refractory Classic Hodgkin Lymphoma: A Phase 2 Study. (PubMed, Blood Adv) - P2 | "Here, we report the efficacy and safety of camidanlumab tesirine (Cami), an anti-CD25 antibody-drug conjugate, in patients with relapsed/refractory cHL following brentuximab vedotin/programmed cell death protein 1 inhibitor therapies from the phase 2 ADCT-301-201 study. Cami was efficacious in this heavily pretreated population; however, the efficacy was overshadowed by substantial issues with the safety profile. NCT04052997."

Journal • P2 data • Bone Marrow Transplantation • Classical Hodgkin Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Infectious Disease • Lymphoma • Oncology • Transplantation

Targeting CD25+ lymphoma cells with the antibody-drug conjugate camidanlumab tesirine as a single agent or in combination with targeted agents. (PubMed, Br J Haematol) - "When camidanlumab tesirine-containing combinations were evaluated in four T-cell lymphoma models, the most active partners were everolimus, copanlisib, venetoclax, vorinostat, and pralatrexate, followed by bortezomib, romidepsin, bendamustine, and 5-azacytidine. The strong camidanlumab tesirine single-agent anti-lymphoma activity and the in vitro synergisms with targeted agents identify potential combination partners for future clinical studies."

Combination therapy • Journal • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • IL2RA

Study of ADCT-301 in Patients With Selected Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=78 | Terminated | Sponsor: ADC Therapeutics S.A. | Phase classification: P1b ➔ P1

Metastases • Monotherapy • Phase classification • Bladder Cancer • Breast Cancer • Colorectal Cancer • Esophageal Cancer • Fallopian Tube Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatology • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Triple Negative Breast Cancer • MSI

Camidanlumab Tesirine Plus Pembrolizumab Produces Responses But Increases Immune Toxicities in Select Solid Tumors (OncLive) - P1 | N=78 | NCT03621982 | Sponsor: ADC Therapeutics S.A. | "Treatment with the anti-CD25 antibody-drug conjugate (ADC) camidanlumab tesirine (ADCT-301) was deemed well tolerated as a monotherapy and produced encouraging responses when administered with pembrolizumab (Keytruda) in select pretreated patients with advanced solid tumors. However, the combination was associated with an increase in immune-related adverse effects (AEs), according to findings from a phase 1 trial (NCT03621982) presented at the 2023 SITC Annual Meeting....In the monotherapy cohort (n = 44), 25.0% of patients achieved stable disease (SD). No patients achieved an objective response, and the disease control rate (DCR) was 25.0%. Conversely, 30.3% of patients in the combination cohort (n = 34) achieved SD, 3.0% of patients achieved a complete response (CR), and 12.1% of patients achieved a partial response (PR). The DCR in this cohort was 45.5%. Notably, all 5 responders had ovarian or fallopian cancer."

P1 data • Solid Tumor

The optimal management of relapsed and refractory Hodgkin lymphoma: post-brentuximab and checkpoint inhibitor failure. (PubMed, Hematology Am Soc Hematol Educ Program) - "Targeted therapies, including the antibody drug conjugate, camidanlumab tesirine, and transcriptional agents such mammalian target of rapamycin and histone deacetylase inhibitors have shown some potential in patients with refractory disease. Clinical trials with cellular therapies, including chimeric antigen receptor T cells targeting CD30 and allogeneic natural killer cells combined with AFM13, a CD30/CD16a-bispecific antibody, have shown promising results. The availability of more therapeutic options for this patient population is eagerly awaited."

Checkpoint inhibition • Journal • Bone Marrow Transplantation • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology • Transplantation • FCGR3A • mTOR • TNFRSF8

Results of a phase 1 study investigating camidanlumab tesirine as monotherapy and in combination with pembrolizumab in patients with selected advanced solid tumors (SITC 2023) - P1b | "The combination of Cami with pembrolizumab is associated with an increase rate of skin and immune-related AEs. The combination shows encouraging results in heavily pre-treated ovarian cancer pts."

Clinical • Combination therapy • Metastases • Monotherapy • P1 data • Oncology • Ovarian Cancer • Solid Tumor • CD8

What's new in the use of antibody-drug conjugates (ADCs) delivering pyrrolobenzodiazepine (PBD) DNA cross-linkers for cancer therapy? (PubMed, Expert Opin Biol Ther) - No abstract available

Journal • Oncology

ADC Therapeutics Reports Second Quarter 2023 Financial Results and Provides Business Updates (GlobeNewswire) - "ADCT-901 (targeting KAAG1): Initial data from Phase 1 study in 1H 2024. ADCT-601 (targeting AXL): Initial data from Phase 1 study in 1H 2024. ADCT-602 (targeting CD22): Additional data from Phase 1 study in 1H 2024....R&D expenses were $31.9 million for the quarter ended June 30, 2023, compared to $48.5 million for the same quarter in 2022. R&D expenses decreased due to less investment in Cami (camidanlumab tesirine) due to the completion of the Phase 2 study in 2022 and the Company’s decision to seek a partner to progress the program, as well as less investment in other development programs."

Commercial • P1 data • Oncology • Solid Tumor

"the preprint of our work on targeting CD25+ #lymphoma cells with the ADC camidanlumab tesirine is now available in ⁦@biorxivpreprint⁩ ⁦@IOR_Bellinzona⁩ ⁦@USI_en⁩ ⁦@EnteOspedaliero⁩ ⁦@AnastasiosStat2⁩ ⁦@CascioneLuciano⁩ https://t.co/MxYXwmKWUe" (@frbertoni)

Preprint • Hematological Malignancies • Lymphoma • Oncology • IL2RA

ADCT-301 in Patients With R/R AML, MDS, or MDS/MPN (clinicaltrials.gov) - P2 | N=3 | Terminated | Sponsor: Gwynn Long, M.D. | N=10 ➔ 3 | Trial completion date: Dec 2024 ➔ Nov 2022 | Recruiting ➔ Terminated | Trial primary completion date: Dec 2024 ➔ Nov 2022; ADCT is reallocating all resources to the phase III program.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology

CAMIDANLUMAB TESIRINE: UPDATED EFFICACY AND SAFETY IN AN OPEN-LABEL, MULTICENTER, PHASE 2 STUDY OF PATIENTS WITH RELAPSED OR REFRACTORY CLASSICAL HODGKIN LYMPHOMA (R/R CHL) (EHA 2022) - P2 | "Methods Pts with R/R cHL and ≥3 prior systemic therapies, including brentuximab vedotin (BV) and anti-PD-1 (≥2 therapies if hematopoietic cell transplantation [HCT] ineligible), were enrolled. Conclusion With median follow-up of 10.7 mos, Cami demonstrated an ORR of 70.1% (CR: 33.3%) in heavily pretreated R/R cHL after BV and PD-1 blockade failure, with an encouraging median DOR of 13.7 mos and median PFS of 9.1 mos. Safety is consistent with prior findings, including similar incidence rates of GBS/polyradiculopathy."

Clinical • P2 data • Anemia • Aplastic Anemia • Diabetes • Fatigue • Hematological Disorders • Hematological Malignancies • Hepatology • Hodgkin Lymphoma • Immunology • Inflammation • Liver Failure • Lymphoma • Metabolic Disorders • Nephrology • Neutropenia • Oncology • Renal Disease • Thrombocytopenia • Transplantation • Type 1 Diabetes Mellitus

Camidanlumab Tesirine: Updated Efficacy and Safety in an Open-Label, Multicenter, Phase 2 Study of Patients With Relapsed or Refractory Classical Hodgkin Lymphoma (R/R cHL) (SOHO 2022) - P1, P2 | " Patients with R/R cHL and 3 prior systemic therapies including brentuximab vedotin and anti–PD-1 were enrolled. Cami demonstrated an ORR of 70.1% (CR: 33.3%) with an encouraging median DOR of 13.7 months and median PFS of 9.1 months. Safety is consistent with prior fi ndings, including similar incidence rates of GBS/polyradiculopathy. Abstract accepted/presented at the EHA 2022 Congress; Funding: ADC Therapeutics SA; medical writing: CiTRUS Health Group."

Clinical • P2 data • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology

HL-339 Camidanlumab Tesirine: Updated Efficacy and Safety in an Open-Label, Multicenter, Phase 2 Study of Patients With Relapsed or Refractory Classical Hodgkin Lymphoma (R/R cHL). (PubMed, Clin Lymphoma Myeloma Leuk) - P1, P2 | "Cami demonstrated an ORR of 70.1% (CR: 33.3%) with an encouraging median DOR of 13.7 months and median PFS of 9.1 months. Safety is consistent with prior findings, including similar incidence rates of GBS/polyradiculopathy. Abstract accepted/presented at the EHA 2022 Congress; Funding: ADC Therapeutics SA; medical writing: CiTRUS Health Group."

Journal • P2 data • P2 data • Fatigue • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Neutropenia • Oncology • Renal Disease • Thrombocytopenia • Transplantation

ADC Therapeutics Reports First Quarter 2023 Financial Results and Provides Business and Strategy Update (Businesswire) - "ADCT-602 (targeting CD22): Additional data from Phase 1 study in 1H 2024....R&D expenses were $39.5 million for the quarter ended March 31, 2023, compared to $49.0 million for the same quarter in 2022. R&D expenses decreased due to less investment in Cami and other programs."

Commercial • P1 data • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

Study to Evaluate the Efficacy and Safety of Camidanlumab Tesirine (ADCT-301) in Patients With Relapsed or Refractory Hodgkin Lymphoma (clinicaltrials.gov) - P2 | N=117 | Completed | Sponsor: ADC Therapeutics S.A. | Terminated ➔ Completed

Trial completion • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology

Study to Evaluate the Efficacy and Safety of Camidanlumab Tesirine (ADCT-301) in Patients With Relapsed or Refractory Hodgkin Lymphoma (clinicaltrials.gov) - P2 | N=117 | Terminated | Sponsor: ADC Therapeutics S.A. | Trial completion date: May 2024 ➔ Jan 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jul 2022 ➔ Jan 2023; Administrative decision.

Trial completion date • Trial primary completion date • Trial termination • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology

Exploratory Analysis of Factors Influencing Efficacy and Safety of Camidanlumab Tesirine: Data from the Open-Label, Multicenter, Phase 2 Study of Patients with Relapsed or Refractory Classical Hodgkin Lymphoma (R/R cHL) (ASH 2022) - P2 | "Introduction: Despite most patients with cHL being cured with standard therapies, a proportion of patients are refractory or relapse after first- and second-line treatments (1L/2L), including stem cell transplantation, and there are limited treatment options available after failure of brentuximab vedotin (BV) and PD-1 blockade. Evidence from preliminary subgroup analyses suggests that response to Cami was independent of age, sex, and response to and timing of last PD-1 inhibitor. Differences in Cami's safety and efficacy were noted by prior transplant and region. Although a difference in CRR was observed between NA and EU, this did not result in a difference in mDOR or ORR between the two regions."

Clinical • IO biomarker • P2 data • Bone Marrow Transplantation • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology • Transplantation

Pre-clinical characterization of the mechanism of action of a CD25-targeted pyrrolobenzodiazepine dimer-based antibody-drug conjugate targeting regulatory T cells in solid cancers (SITC 2019) - P1b; "In conclusion, these new data show that sur301 is able to mediate potent Tregs depletion without affecting Teffs. Together with our previous data [4], these results suggest that sur301's mode of action is at least in part mediated by Tregs depletion while Teffs are not affected. Translation of these pre-clinical data in the clinic is currently being investigated in a phase I trial evaluating the efficacy of camidanlumab tesirine (ADCT-301), a PBD-based ADC targeting human CD25, in patients with selected advanced solid tumors (NCT03621982)."

Oncology • Solid Tumor • IL2RA

Phase 1b dose-escalation and dose-expansion study to evaluate safety, tolerability, pharmacokinetics, and antitumor activity of ADCT-301 (Camidanlumab Tesirine) in patients with advanced solid tumors (SITC 2018) - P1; "The study plans to enroll up to 50 patients with an expected start in Q3 2018. Conclusions A new Phase 1 study is planned to assess the safety and preliminary efficacy of Cami-T for the management of advanced solid tumors."

Clinical • IO biomarker • P1 data • PK/PD data • Colorectal Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Hodgkin Lymphoma • Leukemia • Lung Cancer • Lymphoma • Melanoma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Ovarian Cancer • Thoracic Cancer • Triple Negative Breast Cancer

[VIRTUAL] Combination of Camidanlumab Tesirine, a CD25-Targeted ADC, with Gemcitabine Elicits Synergistic Anti-Tumor Activity in Preclinical Tumor Models (ASH 2020) - P1b, P2 | "Synergistic anti-tumor activity was also demonstrated in a colorectal cancer model using CD25-ADC, a mouse-cross-reactive version of camidanlumab tesirine, in combination with gemcitabine. Altogether, these novel pre-clinical data warrant translation of the combination between camidanlumab tesirine and gemcitabine into the clinic."

Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • IL2RA

[VIRTUAL] Classical Hodgkin Lymphoma: Answers to the Important Management Questions in 2021 (SOHO 2021) - "The addition of brentuximab vedotin in the management of early-stage HL is investigational, but the phase Iidata are encouraging, and a randomized study comparing ABVD ×3 ± RT versus BV-AVD ×3 ± RT is beginning...ABVD for 2 cycles is initiated, and if there is an excellent response, then it is continued for 4 more cycles, many times dropping bleomycin...Although a subsequent study comparing BV-AVD to PET-adapted therapy is not planned, there is an ongoing study comparing BV-AVD to nivolumab-AVD that is nearly 50% accrued...Prior to the introduction of BV and CPI, patients requiring salvage therapy typically received combination treatment that included cisplatin or carboplatin, such as ICE or DHAP...Camidanlumab Tesirine, a human IgG1 anti-CD25 antibody- drug conjugate, has a different warhead than BV...AFM13 was first studied in HL patients as monotherapy in a dose-escalating phase 1 clinical study for patients with heavily pre-treated HL with minimal..."

Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19 • FCGR3A • FDG PET • TNFRSF8

INTERIM DATA FROM THE FIRST CLINICAL STUDY OF ADCT-301, A NOVEL PYRROLOBENZODIAZAPINE-BASED ANTIBODY DRUG CONJUGATE, IN RELAPSED/REFRACTORY HODGKIN/NON-HODGKIN LYMPHOMA (ICML 2017) - P1; "This dose escalation and expansion study will identify the MTD of ADCT-301 and provide a preliminary assessment of its single-agent anti-tumor activity and toxicity profile in R/R HL and NHL. Dose escalation (part 1) is continuing. Further initial safety, tolerability, and efficacy results are expected later this year."

Biosimilar • Diffuse Large B Cell Lymphoma • Immunology • Leukemia

CD25, Soluble CD25, and CCL17 As Potential Predictors of Clinical Response to Camidanlumab Tesirine in Patients with Relapsed/Refractory Classical Hodgkin Lymphoma (ASH 2022) - P2 | "Higher median tumor cell CD25 H-score was seen in responders vs nonresponders in all and recent biopsies but the differences did not reach significance. These data warrant further investigations as phase 1 data showed significantly higher tumor CD25 expression in responders (Hamadani, et al. 2021)."

Clinical • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology • IL2RA