On May 19, 2021 I-Mab (the "Company") (Nasdaq: IMAB), a clinical stage biopharmaceutical company committed to the discovery, development and commercialization of novel biologics, reported that an abstract detailing clinical data from its U.S. phase 1 study of uliledlimab in combination with atezolizumab (TECENTRIQ) in patients with advanced cancer will be presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place June 4-8, 2021 (Press release, I-Mab Biopharma, MAY 19, 2021, View Source [SID1234580324]). The abstract has been selected as one of the Top 12 abstracts for poster discussion during the Developmental Therapeutics – Immunotherapy session.

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Uliledlimab is a humanized CD73 antibody and is designed to counter the adenosine-mediated immunosuppressive tumor microenvironment, rendering anti-tumor immune cells to act more effectively in response to checkpoint immunotherapies. Preclinical studies have shown that when combined with a PD-(L)1 antibody, uliledlimab exhibited a superior and synergistic inhibitory effect on tumor growth versus PD-(L)1 mono-therapy. Uliledlimab is a highly differentiated CD73 antibody that binds to a unique epitope of CD73 to confer pharmacological advantages by avoiding the "hook effect" commonly seen with other CD73 antibodies.

The U.S. phase 1 dose escalation study of uliledlimab in combination with atezolizumab showed that the treatment is safe and well tolerated with no dose-limiting toxicity. All treatment related adverse events were either grade 1 or grade 2. Uliledlimab demonstrated a linear pharmacokinetic (PK) profile and reached full receptor occupancy on B cells at the middle and high dose levels with no "hook effect." Patients who participated in the study had advanced cancers and exhausted other cancer therapies. Among the 13 efficacy-evaluable patients dosed at ≥ 10 mg/kg, three patients had complete or partial responses (objective response rate = 23%) and three had stable disease (disease control rate = 46%). The clinical activity was observed in both PD-(L)1 treatment naïve and refractory cancer patients, including one partial response patient who previously failed nivolumab. Tumor types of patients who had complete or partial responses or stable disease included ovarian clear cell carcinoma, non-small cell lung cancer and a few other cancers. The three responders were identified as the only patients who exhibited higher co-expression of tumor CD73 and PD-L1 as compared to non-responders, indicating a correlation between higher CD73 expression and clinical activity of uliledlimab and a potential role of CD73 as a predictive biomarker to warrant further investigation.

Details of the poster discussion session are as follows:

Abstract No.

2511

Poster Title

Preliminary safety, pharmacokinetics (PK), pharmacodynamics (PD) and clinical efficacy of uliledlimab (TJ004309), a differentiated CD73 antibody, in combination with atezolizumab in patients with advanced cancer

Poster Discussion Session

Developmental Therapeutics – Immunotherapy

Presentation Date and Time

June 4, 2021, 9:00 AM (ET)

Presenting Author

Dr. Francisco Robert, Professor of Medicine, University of Alabama-Birmingham

"Despite recent breakthroughs with PD-1/PD-L1 therapies, clinical non-response rates to such treatments remain high in cancer patients. Uliledlimab, through its unique mechanism of action, has shown its promise to address this unmet medical need by breaking tumor resistance to immunotherapies through combination therapy," said Dr. Joan Shen, CEO of I-Mab. "The results from this phase 1 study are very encouraging in terms of potential therapeutic role of uliledlimab to treat multiple cancers, especially in patients who do not respond to PD-1/PD-L1 therapies. The differentiated properties of uliledlimab may provide additional pharmacological and treatment advantages, and we look forward to advancing the development of uliledlimab both globally and in China."

In parallel development, I-Mab has made significant progress in clinical trials in China to evaluate uliledlimab in combination with toripalimab (TUOYI) in patients with advanced or metastatic cancers, including non-small cell lung cancer, who are refractory to or intolerant of available therapies.

I-Mab will host an investor call on June 7, 2021 to discuss the clinical data presented at the conference. Details of conference call and webcast information will be provided subsequently.

About Uliledlimab (TJD5)

Uliledlimab (TJD5) is a differentiated, humanized antibody against CD73, an ecto-enzyme expressed on stromal cells and tumors that converts extracellular adenosine monophosphate (AMP) to adenosine. Adenosine in turn binds to adenosine receptors on relevant immune cells and inhibits anti-tumor immune responses in tumor microenvironment. Uliledlimab is expected to offer clinical benefit by suppressing tumor growth in concert with checkpoint therapies such as PD-(L)1 antibodies. Uliledlimab is effective in anti-tumor activities through a unique intra-dimer binding, leading to differentiated and favorable functional properties as evident in preclinical studies.

On May 19, 2021 Oncopeptides AB (publ) (Nasdaq Stockholm: ONCO), a global biotech company focused on the development of therapies for difficult-to-treat hematological diseases, reported that three abstracts with data on melflufen (INN melphalan flufenamide) in relapsed refractory multiple myeloma, RRMM, have been accepted by the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), ASCO (Free ASCO Whitepaper), and have now been published online (Press release, Oncopeptides, MAY 19, 2021, View Source [SID1234580323]). The clinical data presentations include updates on Oncopeptides’ ANCHOR and LIGHTHOUSE studies as well as a pooled analysis of the O-12-M1 and HORIZON studies in patients who have been exposed to or become refractory to prior alkylators.

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"The phase 1/2 ANCHOR study of melflufen plus dexamethasone in combination with either daratumumab or bortezomib shows encouraging clinical activity in heavily pre-treated patients with relapsed refractory multiple myeloma, and the optimal dose of melflufen has now been established for both regimens," says Klaas Bakker, MD, PhD, Executive Vice President and Chief Medical Officer, Oncopeptides AB. "We will now complete patient enrolment in the bortezomib arm, while the daratumumab arm is already fully accrued, as presented at the American Hematology Association meeting in December 2020, where updated safety and efficacy data from ANCHOR were presented. The data presented here at ASCO (Free ASCO Whitepaper) data clearly support further development of melflufen in triplet regimens and reinforce the rational for the ongoing phase 3 LIGHTHOUSE study, comparing melflufen plus dexamethasone in combination with subcutaneous daratumumab with daratumumab alone."

Below is a brief description of the abstracts that have been accepted by the ASCO (Free ASCO Whitepaper). They will be available online at View Source, on May 19th at 23:00 (CET).

1. ANCHOR (OP-104): MELFLUFEN PLUS DEXAMETHASONE AND BORTEZOMIB IN RELAPSED/REFRACTORY MULTIPLE MYELOMA PATIENTS
The ANCHOR study determined that the optimal dose of melflufen is 30 mg plus dexamethasone and bortezomib and the results showed clinical activity in heavily pretreated RRMM patients. Recruitment for this study is ongoing and updated data including efficacy and safety will be presented at ASCO (Free ASCO Whitepaper).

2. LIGHTHOUSE (OP-108): A PHASE 3 STUDY OF MELFLUFEN IN COMBINATION WITH DEXAMETHASONE AND DARATUMUMAB IN RELAPSED/REFRACTORY MULTIPLE MYELOMA PATIENTS
The phase 3 LIGHTHOUSE study is a randomized, controlled, open-label study of melflufen plus dexamethasone in combination with daratumumab vs daratumumab alone in patients with RRMM previously treated with an immunomodulatory agent and a proteasome inhibitor, similar to the indication for daratumumab monotherapy. The primary objective is superiority of PFS. Key secondary endpoints include ORR (≥ PR), DOR, and safety. Patient recruitment is ongoing with a planned enrolment of 240 patients.

3. A POOLED ANALYSIS OF THE O-12-M1 AND HORIZON STUDIES: MELFLUFEN PLUS DEXAMETHASONE IN RELAPSED/REFRACTORY MULTIPLE MYELOMA PATIENTS (RRMM) WHO ARE EXPOSED OR REFRACTORY TO PRIOR ALKYLATORS
This pooled analysis of the O-12-M1 and HORIZON studies showed that melflufen in combination with dexamethasone showed meaningful efficacy and demonstrated a clinically manageable safety profile in patients with RRMM who had been exposed or become refractory to prior alkylators.

PEPAXTO (melphalan flufenamide, also known as melflufen), in combination with dexamethasone, was granted accelerated approval by the FDA on February 26, 2021, for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one CD38-directed monoclonal antibody.

For more information, please contact:

Rolf Gulliksen, Global Head of Corporate Communications, Oncopeptides AB (publ)
E-mail: [email protected]
Cell phone: + 46 70 262 96 28

Linda Holmström, Director of Investor Relations, Oncopeptides AB (publ)
E-mail: [email protected]
Cell phone: +46 70 873 40 95

About melphalan flufenamide

Melphalan flufenamide, also known as melflufen, is a first-in-class peptide-drug conjugate that targets aminopeptidases and rapidly releases alkylating agents inside cancer cells. Aminopeptidases are overexpressed in multiple myeloma cells and are associated with advanced disease and tumor mutational burden. Targeting aminopeptidases causes selective activity in cancer cells, sparing healthy cells.

In the US, PEPAXTO (melphalan flufenamide) is indicated in combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma, who have received at least four prior lines of therapy and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one CD38-directed monoclonal antibody.

On May 19, 2021 Transcenta Holding Limited ("Transcenta"), a global biotherapeutics company with fully-integrated capabilities in discovery, development and manufacturing of antibody-based therapeutics, reported that the updated Phase I clinical study (NCT04272944) data on the safety and efficacy of MSB2311, a pH-dependent PD-L1 antibody, in Chinese patients with advanced solid tumors and hematological malignancies have been presented as an abstract online publication at the 2021 Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (Abstract #e14547, 5:00 PM, U.S. East Time, Wednesday, May 19, 2021) (Press release, Transcenta, MAY 19, 2021, View Source [SID1234580322]).

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The study, presented at the 2021 ASCO (Free ASCO Whitepaper) annual meeting by abstract, was led by Professor Lin Shen from Beijing Cancer Hospital, and was a Phase I study of MSB2311 with a unique pH-dependent antigen binding property in Chinese patients with advanced solid tumors and lymphoma. Its primary objectives were to evaluate the safety and tolerability and to identify the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D). The secondary objectives included the assessment of pharmacokinetic parameter, immunogenicity, and preliminary anti-cancer activity per RECIST version 1.1.

The study included a dose escalation Phase and a dose expansion Phase. In the dose escalation Phase, MSB2311 was given at dose levels of 3, 10, and 20mg/kg intravenously every 3 weeks. At the dose expansion Phase, patients with biomarker expression, including EBV+, PD-L1+ (TPS≥50%), MSI-High or TMB-High (≥10muts/Mb), were dosed at 20mg/kg Q3W or 10mg/kg Q2W.

As of data cutoff by Aug 31, 2020, 33 Chinese patients had been treated, including 27 heavily pre-treated solid tumor patients and 6 lymphoma patients. No dose limiting toxicity was reported and MTD has not been reached. The most common AEs (>20%) included: anemia, hypothyroidism, aspartate aminotransferase elevated, proteinuria and weight loss. 13 patients (39.4%) experienced grade 3 AEs, and 6 patients (18.2%) experienced serious adverse events (SAEs). No treatment related grade 4 or 5 AEs was reported.

Of the 17 efficacy evaluable solid tumor patients with biomarker expression, 6 achieved confirmed partial response with an ORR of 35%: 2/8 (25%) at 10mg/kg Q2W and 4/9 (44%) at 20mg/kg Q3W. Additionally, one patient achieved sustained iPR per iRECIST. 4 out of 7 responding patients (including one iPR) achieved tumor shrinkage of more than 50%, 3 of them got durable response (≥24 weeks). 1 out of 6 lymphoma patients achieved PR.

"In recent years, tumor immunotherapy has gradually become a research hotspot in the field of tumor treatment. It has played a great role in the treatment of tumors, and we have been making efforts in this area," said Professor Lin Shen, the leading investigator from Beijing Cancer Hospital. "Patients with metastatic solid tumors or selected lymphoma progressed on or after standard treatments were enrolled in this Phase I study. This Phase I study showed promising preliminary efficacy and tolerability of MSB2311 in patients with advanced solid tumors and hematological malignancies."

"MSB2311 demonstrated a manageable safety profile and promising antitumor activity in patients with advanced solid tumors and lymphomas." said Dr. Michael Shi, EVP, Head of Global R&D and CMO of Transcenta. "We are excited to see how our in-house developed medicines can help to benefit the patients. We will continue to forge ahead with our commitment to differentiated and affordable biologics for patients around the world."

About MSB2311

MSB2311 is an investigational humanized PD-L1 with pH dependent binding property. PD-L1 is involved in inhibiting the immune system’s response to fight cancer. MSB2311 blocks the interaction between PD-L1 and PD-1, which reactivates the suppressed or exhausted anti-tumor effector T cell function in the tumor microenvironment. MSB2311 employs engineered IgG1 which lacks FcR binding. In addition, the binding of MSB2311 to PD-L1 results in internalization of MSB2311 and MSB2311 can dissociate from bound PD-L1 in endosome with pH level lower than 5.5. This allows MSB2311 to be recycled to plasma membrane and be reused to bind with PD-L1 on another tumor cell or immune cell. Results from preclinical studies demonstrate that MSB2311 can inhibit tumor growth of PD-L1 expressing tumor cells in syngeneic mouse-model. Two Phase 1 studies of MSB2311 have been completed in the US and China. MSB2311 is currently to be tested in Phase 2 trial in patients with solid tumors expressing selected biomarker in China.

On May 19, 2021 Ascentage Pharma (6855.HK), a globally focused, clinical-stage biotechnology company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported that an abstract reporting on the first-in-human study of the Bcl-2 inhibitor, lisaftoclax (APG-2575), in patients with relapsed/refractory chronic lymphocytic lymphoma/small lymphocytic lymphoma (R/R CLL/SLL) and other hematologic malignancies has been published in the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting’s official website (Press release, Ascentage Pharma, MAY 19, 2021, View Source;ascentage-pharma-to-announce-updated-data-of-lisaftoclax-apg-2575-demonstrating-an-orr-of-around-80-and-therapeutic-potential-in-patients-with-rr-cllsll-in-oral-presentation-301295527.html [SID1234580321]). Results from this global Phase I study demonstrated an ORR of 85.7%, and favorable tolerability and safety profiles in patients with R/R CLL /SLL.

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The updated results from this study will be released in an oral presentation at the ASCO (Free ASCO Whitepaper) Annual Meeting convening on June 4 to 8, 2021. This year, abstracts reporting on four clinical studies of the Ascentage Pharma’s three apoptosis-target drug candidates have been selected for presentations at the ASCO (Free ASCO Whitepaper) Annual Meeting, and two have been selected for oral presentations.

Drug Candidate

Abstract Title

Abstract #

Format

Lisaftoclax

(APG-2575)

First-in-human study of lisaftoclax (APG-2575), a novel Bcl-2 inhibitor (Bcl-2i), in patients (pts) with relapsed/refractory (R/R) CLL and other hematologic malignancies (HMs)

7502

Oral

Presentation

Alrizomadlin

(APG-115)

Preliminary results of a phase II study of alrizomadlin (APG-115), a novel, small-molecule MDM2 inhibitor, in combination with pembrolizumab in patients (pts) with unresectable or metastatic melanoma or advanced solid tumors that have failed immuno-oncologic (I-O) drugs

2506

Oral

Presentation

Trial in progress: A phase I/II trial of novel MDM2 inhibitor alrizomadlin (APG-115), with or without platinum chemotherapy, in patients with p53 wild-type salivary gland carcinoma

TPS6094

Poster

Presentation

Pelcitoclax

(APG-1252)

Trial in progress: A multicenter phase Ib/II study of pelcitoclax (APG-1252) in combination with paclitaxel in patients with relapsed/refractory small-cell lung cancer (R/R SCLC)

TPS8589

Poster

Presentation

"As a Bcl-2 inhibitor that has demonstrated efficacy, lisaftoclax is the second in the world and the first in China. These data of lisaftoclax suggest the potential for a safe, efficacious, and ‘patient-friendly’ treatment alternative for patients with R/R CLL and other hematologic malignancies," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "Moreover, these results which will be presented at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting are a testament to our progress in advancing the research and development of apoptosis-targeted therapeutics. We will strive to further accelerate global clinical development programs of these novel therapeutics to benefit patients in China and around the world as early as possible."

Those abstracts to be presented at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting are as follows (two abstracts on APG-115 are simultaneously published in a separate press release):

First-in-human study of lisaftoclax (APG-2575), a novel Bcl-2 inhibitor (Bcl-2i), in patients (pts) with relapsed/refractory (R/R) CLL and other hematologic malignancies (HMs)

Format: Oral Presentation
Abstract: #7502
Time: 11:30 – 14:30 EDT, June 7, 2021
Session Track: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia
Highlights:
This first-in-human global Phase I study assessed the safety, pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and maximum tolerated dose (MTD)/recommended Phase II dose (RP2D) of lisaftoclax in patients with R/R CLL and other HMs. Lisaftoclax was orally administered once daily in a 28-day cycle. Patients with CLL or intermediate-high tumor lysis syndrome (TLS) risk were initiated on a daily ramp-up schedule until the dose assigned before the study cycles.
As of January 7, 2021, 35 patients had been enrolled and treated with lisaftoclax at doses ranging from 20 to 1,200 mg, with a median of 2 (range: 1-13) prior lines of treatment. These patients had been diagnosed with R/R CLL/SLL (n=15), multiple myeloma (MM, n=6), follicular lymphoma (FL, n=5), Waldenström macroglobulinemia (WM, n=4); and either acute myeloid leukemia (AML), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), myelodysplastic syndromes (MDS), or hairy cell leukemia (HCL) (n=1 each).
Lisaftoclax was well tolerated, with manageable adverse events (AEs). No dose-limiting toxicity (DLT) was observed even at the maximum dose of 1,200 mg. The MTD has not been reached, and no laboratory or clinical TLS has been reported. Hematologic treatment-related adverse events (TRAEs) of any grade in over 10% patients included neutropenia and anemia, while nonhematologic TRAEs included fatigue, diarrhea, and nausea.
12 of 14 evaluable patients with R/R CLL/SLL achieved partial response (PR), for an ORR of 85.7% and a median time to response of 3 treatment cycles (range: 2-7). Absolute lymphocyte counts (ALCs) were reduced at lisaftoclax doses as low as 20 mg/day.
The preliminary PK profile showed that exposures increased with lisaftoclax doses from 20 to 1,200 mg (average half-life: 4-5 hours). On BH3 profiling, lisaftoclax rapidly triggered changes in Bcl-2 complex in CLL/SLL patient samples, which were consistent with rapid clinical reductions in ALCs.
In conclusion, efficacy and safety data showed that the Bcl-2 inhibitor lisaftoclax offers a potential alternative treatment for patients with R/R CLL/SLL and other HMs, with a daily ramp-up schedule that may be more patient-friendly and a favorable preliminary safety profile.
Trial in progress: A multicenter phase Ib/II study of pelcitoclax (APG-1252) in combination with paclitaxel in patients with relapsed/refractory small-cell lung cancer (R/R SCLC)

Format: Poster Presentation
Abstract: #TPS8589
Time: 09:00 EDT, June 4, 2021
Session Track: Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers
Highlights:
This open-label, multicenter Phase Ib/II study is assessing the safety of preliminary efficacy of pelcitoclax in combination with paclitaxel in patients with R/R SCLC.
Pelcitoclax is being administered by intravenous (IV) infusion on Days 1, 8, and 15, with paclitaxel at the fixed-dose of 80 mg/m2 on Days 1 and 8 of a 21-day cycle.
The primary endpoints of the Phase Ib part of this study include MTD and RP2D. The efficacy of pelcitoclax combined with paclitaxel will be determined in the Phase II part of the study using a Simon two-stage design, with ORR as the primary endpoint. Other endpoints of the Phase II study include PK, progression-free survival, and overall survival.
This study was designed to enroll 58 patients. As of February 8, 2021, 15 patients have been enrolled.
About Lisaftoclax (APG-2575)

Lisaftoclax is a novel, orally administered small-molecule Bcl-2‒selective inhibitor being developed by Ascentage Pharma. Lisaftoclax is designed to treat hematologic malignancies and solid tumors by selectively blocking antiapoptotic protein Bcl-2 to restore the normal apoptosis process in cancer cells. Lisaftoclax is the first China-developed Bcl-2 inhibitor entering clinical development in China. At present, lisaftoclax has been cleared and approved to enter multiple Phase Ib/II studies in the US, China, and Australia, and is being developed globally for the treatment of multiple hematologic malignancies.

About Pelcitoclax (APG-1252)

Pelcitoclax is a novel, highly potent, small-molecule drug designed to restore apoptosis through selective inhibition of Bcl-2 and Bcl-xL proteins. Multiple Phase Ib/II studies of pelcitoclax as a single agent or in combinations for the treatment of a range of advanced tumors, including small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), are being conducted in China, Australia, and the US.

On May 19, 2021 ADC Therapeutics SA (NYSE:ADCT), a commercial-stage biotechnology company leading the development of novel antibody drug conjugates (ADCs) to treat hematological malignancies and solid tumors, announced today three abstracts have been selected for poster presentations at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, which is being held virtually June 4-8, 2021 (Press release, ADC Therapeutics, MAY 19, 2021, View Source [SID1234580320]).

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"We are pleased that research from our lead programs will be shared with the oncology community at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting," said Jay Feingold, MD, PhD, Senior Vice President and Chief Medical Officer of ADC Therapeutics. "On the heels of the accelerated FDA approval of ZYNLONTA (loncastuximab tesirine-lpyl), we continue to advance our deep pipeline to deliver next-generation ADC therapies to patients with hematologic and solid tumor cancers."

Poster Presentation Details

Title: Duration of response to loncastuximab tesirine in relapsed/refractory diffuse large B-cell lymphoma by demographic and clinical characteristics: Subgroup analyses from LOTIS 2
Track: Hematologic Malignancies – Lymphoma and Chronic Lymphocytic Leukemia
Date/Time: On demand beginning June 4 at 9 a.m. EDT
Presenter: Paolo F. Caimi, MD, University Hospitals Cleveland Medical Center and Case Comprehensive Cancer Center, Case Western Reserve University
Abstract Number: 7546

Title: Phase 3 randomized study of loncastuximab tesirine plus rituximab versus immunochemotherapy in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): LOTIS-5
Track: Hematologic Malignancies – Lymphoma and Chronic Lymphocytic Leukemia
Date/Time: On demand beginning June 4 at 9 a.m. EDT
Presenter: Mehdi Hamadani, MD, Professor of Internal Medicine at the Medical College of Wisconsin, Division of Hematology & Oncology
Abstract Number: TPS7574

Title: A Phase 1b, open-label, dose-escalation study to evaluate camidanlumab tesirine (Cami) as monotherapy in patients (pts) with advanced solid tumors
Track: Developmental Therapeutics—Immunotherapy
Date/Time: On demand beginning June 4 at 9 a.m. EDT
Presenter: Igor Puzanov, MD, Clinical Professor of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo
Abstract Number: 2556

About ZYNLONTA (loncastuximab tesirine-lpyl)

ZYNLONTA is a CD19-directed antibody drug conjugate (ADC). Once bound to a CD19-expressing cell, ZYNLONTA is internalized by the cell, where enzymes release a pyrrolobenzodiazepine (PBD) payload. The potent payload binds to DNA minor groove with little distortion, remaining less visible to DNA repair mechanisms. This ultimately results in cell cycle arrest and tumor cell death. The U.S. Food and Drug Administration (FDA) has approved ZYNLONTA (loncastuximab tesirine-lpyl) for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from low-grade lymphoma and also high-grade B-cell lymphoma. This indication is approved by the FDA under accelerated approval based on overall response rate and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

The FDA approval was based on data from LOTIS-2, a large (n=145) Phase 2 multinational, single-arm clinical trial of ZYNLONTA for the treatment of adult patients with r/r DLBCL following two or more prior lines of systemic therapy. The trial included a broad spectrum of heavily pre-treated patients (median three prior lines of therapy) with very difficult to treat disease, including patients with high-grade B-cell lymphoma. The trial also enrolled patients who did not respond to first-line therapy, patients refractory to all prior lines of therapy, and patients who had stem cell transplants and CAR-T therapy prior to their treatment with ZYNLONTA. Results from the trial demonstrated an overall response rate (ORR) of 48.3% (70/145 patients), which included a complete response (CR) rate of 24.1% (35/145 patients) and a partial response (PR) rate of 24.1% (35/145 patients). Patients had a median time to response of 1.3 months. At the most recent data cut-off for patients enrolled in the trial, the median duration of response (mDoR) was 12.58 months. In a pooled safety population the most common adverse reactions (≥20%) were thrombocytopenia, gamma-glutamyltransferase increased, neutropenia, anemia, hyperglycemia, transaminase elevation, fatigue, hypoalbuminemia, rash, edema, nausea and musculoskeletal pain. In LOTIS-2, the most common (≥10%) grade ≥3 treatment-emergent adverse events were neutropenia (26.2%), thrombocytopenia (17.9%), gamma-glutamyltransferase increased (17.2%) and anemia (10.3%).

ZYNLONTA is being evaluated in combination for earlier lines of therapy and as a monotherapy in other B-cell malignancies.

About Camidanlumab Tesirine (Cami)

Camidanlumab tesirine (Cami, formerly ADCT-301) is an antibody drug conjugate (ADC) comprised of a monoclonal antibody that binds to CD25 (HuMax-TAC, licensed from Genmab A/S), conjugated to the pyrrolobenzodiazepine (PBD) dimer payload, tesirine. Once bound to a CD25-expressing cell, Cami is internalized into the cell where enzymes release the PBD-based payload killing the cell. This applies to CD25-expressing tumor cells, and also to CD25-expressing Tregs. The intra-tumoral release of its PBD payload may also cause bystander killing of neighboring tumor cells and PBDs have also been shown to induce immunogenic cell death. All of these properties of Cami may enhance immune-mediated anti-tumor activity.

Cami is being evaluated in a pivotal Phase 2 clinical trial in patients with relapsed or refractory Hodgkin lymphoma (HL), as well as in a Phase 1a/1b clinical trial in patients with relapsed or refractory HL and non-Hodgkin lymphoma and a Phase 1b clinical trial as monotherapy and in combination with pembrolizumab in solid tumors.