On June 4, 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, reported updated clinical data from the ZYNLONTA (loncastuximab tesirine-lpyl) Phase 2 LOTIS-2 trial in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) were presented 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, JUN 4, 2021, View Source [SID1234583547]).

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"The maturing duration of response from the ZYNLONTA Phase 2 trial reported at ASCO (Free ASCO Whitepaper) reflects the strong data set that served as the basis of the accelerated FDA approval in April," said Jay Feingold, MD, PhD, Senior Vice President and Chief Medical Officer of ADC Therapeutics. "We are especially encouraged to see this positive trend continue to strengthen in a heavily pre-treated patient population, including patients with double- / triple-hit, advanced stage or transformed DLBCL, DLBCL refractory to first-line therapy, and patients older than 65."

In LOTIS-2, a single-arm, open-label, 145-patient Phase 2 clinical trial in patients with relapsed or refractory DLBCL who had failed ≥2 established therapies, ZYNLONTA demonstrated continued substantial antitumor activity and an acceptable safety profile. Updated results, including analysis of response in high-risk subgroups, were presented in a poster (abstract number: 7546) by Paolo F. Caimi, MD, University Hospitals Cleveland Medical Center and Case Comprehensive Cancer Center, Case Western Reserve University.

Key data at the March 1, 2021 data cut include:

Overall response rate (ORR) was 48.3% and complete response rate (CRR) was 24.8%
Median duration of response (mDoR) of 13.4 months for the 70 responders
Median duration of response not reached for patients with a complete response
Durable responses in high-risk patient groups, including:
Patients with double- / triple-hit or transformed DLBCL each had a median DoR not reached
Patients with advanced stage disease (Stage III-IV) had a median DoR of 12.6 months
Median DoR for older patients was longer than for younger patients (≥75 years, not reached; ≥65 years to <75 years, 12.6 months; <65 years, 9.3 months)
Patients with DLBCL refractory to first-line systemic therapy had a median DoR of 9.6 months compared with 12.6 months for patients who relapsed after responding to initial therapy
No new safety concerns were identified during the study and no increase in toxicity was observed in patients aged ≥65 years compared with patients <65 years
Two additional posters presented at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting:

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 (abstract number: TPS7574)
A Phase 1b, open-label, dose-escalation study to evaluate camidanlumab tesirine (Cami) as monotherapy in patients (pts) with advanced solid tumors (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 13.4 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.

On June 4, 2021 MorphoSys US Inc., a fully owned subsidiary of MorphoSys AG (FSE: MOR; NASDAQ: MOR), and Incyte (NASDAQ:INCY) reported new three-year follow-up data from the ongoing Phase 2 L-MIND study of tafasitamab (Monjuvi(R)) in combination with lenalidomide in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (Press release, MorphoSys, JUN 4, 2021, View Source [SID1234583546]). A total of 80 out of 81 enrolled study patients receiving tafasitamab plus lenalidomide were included in the efficacy analysis at approximately three years follow-up (>=35 months).[1] The long-term analysis, as assessed by an independent review committee (IRC), showed that patients treated with tafasitamab plus lenalidomide had an overall response rate (ORR) of 57.5% (95% CI = 45.9%, 68.5%; 46 out of 80 patients), including a complete response (CR) rate of 40% (32 out of 80 patients). Additionally, the median duration of response (DoR) was 43.9 months (95% CI = 26.1, NR), with a median overall survival (OS) of 33.5 months (95% CI = 18.3, NR) and median progression free survival (PFS) of 11.6 months (95% CI = 6.3, 45.7).

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These data (abstract #7513) are available on demand as part of the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, held virtually June 4-8, 2021, and will be presented as a poster and poster discussion in the Hematologic Malignancies-Lymphoma and Chronic Lymphocytic Leukemia session.

"The three-year efficacy data, combined with the safety and tolerability profile of tafasitamab, further support a therapeutic option for patients with relapsed or refractory DLBCL who are ineligible for transplant – a traditionally difficult-to-treat population," said Gilles Salles, M.D., Ph.D., Lymphoma Service Chief at Memorial Sloan Kettering Cancer Center, and lead investigator of the L-MIND study*. "I am encouraged to see the confirmed favorable outcome of patients in the L-MIND study, which suggest that this combination treatment regimen could potentially offer a paradigm shift and long-term disease control."

The new results – based on an October 30, 2020 data cut-off – build on previous findings showing durable responses and a consistent safety profile of tafasitamab in combination with lenalidomide followed by tafasitamab monotherapy in autologous stem cell transplantation (ASCT)-ineligible patients with relapsed or refractory DLBCL.

"The three-year follow-up data not only show a durable response and consistent safety profile in patients with relapsed or refractory DLBCL treated with tafasitamab plus lenalidomide, it also suggests the combination could potentially lead to durable remission," said Nuwan Kurukulasuriya, Ph.D., Senior Vice President, Global Head of Medical Affairs, MorphoSys. "We are looking forward to sharing these long-term follow-up findings with the scientific community."

"We are pleased that long-term data from the L-MIND study underscore the clinically-significant durable responses that are possible with tafasitamab plus lenalidomide as a treatment for relapsed or refractory DLBCL," said Peter Langmuir, M.D., Group Vice President, Oncology Targeted Therapies, Incyte. "We look forward to continuing to build the body of clinical evidence supporting tafasitamab as a treatment option for patients with DLBCL, as well as exploring other potential indications for tafasitamab through our ongoing research and development program."

In July 2020, the U.S. Food and Drug Administration (FDA) approved Monjuvi(R) (tafasitamab-cxix) in combination with lenalidomide for the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for ASCT. This indication is approved under accelerated approval based on ORR. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). The U.S. approval is based on an efficacy subgroup of 71 patients confirmed by central lab.

The FDA decision represented the first approval of a second-line treatment for adult patients with DLBCL who progressed during or after first-line therapy.

About Diffuse Large B-cell Lymphoma (DLBCL)
DLBCL is the most common type of non-Hodgkin lymphoma in adults worldwide[2], characterized by rapidly growing masses of malignant B-cells in the lymph nodes, spleen, liver, bone marrow or other organs. It is an aggressive disease with about 40% of patients not responding to initial therapy or relapsing thereafter[3], leading to a high medical need for new, effective therapies[4], especially for patients who are not eligible for an autologous stem cell transplant in this setting.

About L-MIND
The L-MIND trial is a single arm, open-label Phase 2 study (NCT02399085) investigating the combination of tafasitamab and lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have had at least one, but no more than three prior lines of therapy, including an anti-CD20 targeting therapy (e.g., rituximab), who are not eligible for high-dose chemotherapy or refuse subsequent autologous stem cell transplant. The study’s primary endpoint is overall response rate (ORR). Secondary outcome measures include duration of response (DoR), progression-free survival (PFS) and overall survival (OS). In May 2019, the study reached its primary completion.

For more information about L-MIND, visit View Source

About Tafasitamab
Tafasitamab is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody. In 2010, MorphoSys licensed exclusive worldwide rights to develop and commercialize tafasitamab from Xencor, Inc. Tafasitamab incorporates an XmAb(R) engineered Fc domain, which mediates B-cell lysis through apoptosis and immune effector mechanism including antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).

Monjuvi(R) (tafasitamab-cxix) is approved by the U.S. Food and Drug Administration in combination with lenalidomide for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

In January 2020, MorphoSys and Incyte entered into a collaboration and licensing agreement to further develop and commercialize tafasitamab globally. Monjuvi(R) is being co-commercialized by Incyte and MorphoSys in the United States. Incyte has exclusive commercialization rights outside the United States.

A marketing authorization application (MAA) seeking the approval of tafasitamab in combination with lenalidomide in the European Union has been validated by the European Medicines Agency (EMA) and is currently under review for the treatment of adult patients with relapsed or refractory DLBCL, including DLBCL arising from low grade lymphoma, who are not candidates for ASCT.

Tafasitamab is being clinically investigated as a therapeutic option in B-cell malignancies in a number of ongoing combination trials.

Monjuvi(R) is a registered trademark of MorphoSys AG.

XmAb(R) is a registered trademark of Xencor, Inc.

Important Safety Information

What are the possible side effects of MONJUVI?

MONJUVI may cause serious side effects, including:

– Infusion reactions. Your healthcare provider will monitor you for infusion reactions during your infusion of MONJUVI. Tell your healthcare provider right away if you get fever, chills, rash, flushing, headache, or shortness of breath during an infusion of MONJUVI.

– Low blood cell counts (platelets, red blood cells, and white blood cells). Low blood cell counts are common with MONJUVI, but can also be serious or severe. Your healthcare provider will monitor your blood counts during treatment with MONJUVI. Tell your healthcare provider right away if you get a fever of 100.4 F (38 C) or above, or any bruising or bleeding.

– Infections. Serious infections, including infections that can cause death, have happened in people during treatments with MONJUVI and after the last dose. Tell your healthcare provider right away if you get a fever of 100.4 F (38 C) or above, or develop any signs and symptoms of an infection.

The most common side effects of MONJUVI include:

– Feeling tired or weak

– Diarrhea

– Cough

– Fever

– Swelling of lower legs or hands

– Respiratory tract infection

– Decreased appetite

These are not all the possible side effects of MONJUVI.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Before you receive MONJUVI, tell your healthcare provider about all your medical conditions, including if you:

– Have an active infection or have had one recently.

– Are pregnant or plan to become pregnant. MONJUVI may harm your unborn baby. You should not become pregnant during treatment with MONJUVI. Do not receive treatment with MONJUVI in combination with lenalidomide if you are pregnant because lenalidomide can cause birth defects and death of your unborn baby.

– You should use an effective method of birth control (contraception) during treatment and for at least 3 months after your final dose of MONJUVI.

– Tell your healthcare provider right away if you become pregnant or think that you may be pregnant during treatment with MONJUVI.

– Are breastfeeding or plan to breastfeed. It is not known if MONJUVI passes into your breastmilk. Do not breastfeed during treatment for at least 3 months after your last dose of MONJUVI.

You should also read the lenalidomide Medication Guide for important information about pregnancy, contraception, and blood and sperm donation.

Tell your healthcare provider about all the medications you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

On June 4, 2021 Cyteir Therapeutics, a leader in the discovery and development of next-generation synthetically lethal therapies for cancer, reported the presentation of an interim analysis of the Phase 1 portion of a first-in-human Phase 1/2 study of CYT-0851 (Press release, Cyteir Therapeutics, JUN 4, 2021, View Source [SID1234583544]). CYT-0851 is an oral, small molecule inhibitor of RAD51-mediated homologous recombination. The presentation was given at an oral session of the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) meeting.

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The Phase 1 portion of the trial began enrolling patients with advanced hematologic cancers and solid tumors in September 2019. Patients were treated with continuous 28-day cycles of increasing oral doses of CYT-0851. The primary objective of the ongoing Phase 1 study is to identify the maximum tolerated dose (MTD). The key secondary objectives are evaluation of the safety, pharmacokinetics, and preliminary anti-tumor activity.

As of the April 6, 2021 data cutoff, 35 patients were treated with CYT-0851 across eight dose-escalation cohorts. Thirty-five patients were evaluable for safety and 21 patients were evaluable for efficacy. Patients had a median of four prior lines of therapy. Twenty-three patients discontinued treatment due to progressive disease (19), patient decision (2), physician decision (1) or adverse event (1). The adverse event that led to discontinuation was an increase in the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) that was secondary to the patient’s cancer.

To date, CYT-0851 has been well-tolerated with 63% of patients reporting no treatment related adverse events. Thirteen patients (37.1%) experienced treatment-related adverse events with most events being low-grade. There have been no reported treatment-related Grade 4 or 5 events. The most common treatment-related adverse events were an increase in blood alkaline phosphatase levels (8.6%), fatigue (8.6%) and nausea (8.6%). There have been no reported dose-limiting toxicities, clinically significant myelosuppression, treatment discontinuations due to treatment-related adverse events, or treatment-related serious adverse events.

At the time of the data cutoff, there were 21 patients who were response evaluable. Three partial responses were observed in patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and soft tissue sarcoma. The patients with DLBCL and FL had confirmed responses according to Lugano criteria and the patient with sarcoma had a response that was unconfirmed according to RECIST. Ten patients had a best response of stable disease and four patients have been on therapy for more than six months, including the three patients that responded to treatment.

The study continues to dose-escalate to identify the MTD and enrollment is ongoing in the 400mg once daily dose cohort. Upon identification of the MTD, a Phase 2 dose will be selected, and the Phase 2 expansion cohorts are expected to begin enrollment in the second half of 2021.

On June 4, 2021 Sorrento Therapeutics, Inc. (Nasdaq: SRNE, "Sorrento") reported that the Company has entered into an additional collaborative agreement with NextGenNK Competence Center-associated research groups at the Department of Medicine, Huddinge, Karolinska Institutet ("KI") in Stockholm, Sweden, aimed at producing novel cell-based therapeutics using natural killer ("NK") cells derived from induced pluripotent stem cells ("iPSCs") (Press release, Sorrento Therapeutics, JUN 4, 2021, View Source [SID1234583543]). Sorrento and KI are collaborative partners in the Competence Center for the development of next-generation NK cell-based cancer immunotherapies ("NextGenNK") coordinated by KI.

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Under the agreement, Sorrento will provide know-how in the core chimeric antigen receptor ("CAR") and dimeric antigen receptor ("DAR") technologies and support the collaborative effort to develop new CAR-NK and DAR-NK candidates, as well as fund the translational validation of the technologies. Multiple product candidates will be developed and tested in the initial phase of the planned work, with the goal that the candidate products will qualify for further human clinical trials.

The foundational Sorrento research assets critical to this program are novel proprietary CAR and DAR constructs identified through Sorrento’s proprietary G-MAB fully human antibody library and previously validated as determinants of cell-based therapy potency against hematologic and solid tumors.

"It is a privilege to continue and extend our collaborative work with the distinguished KI faculty. We are proud to contribute our technologies to produce new optimized off-the-shelf adoptive NK cell immunotherapies," said Dr. Henry Ji, Chairman and CEO of Sorrento. "Our partnership with KI combines our know-how with the expertise of a world-renowned institution in the field of NK cell therapy. These types of partnerships are essential in advancing medicine and bringing new solutions to cancer patients in need."

KI scientists within NextGenNK will establish iPSC-derived NK-based therapeutic candidates utilizing Sorrento’s constructs and DAR technology. Work within KI has contributed to the development of methodologies that consistently generate robust and potent NK cell lineages following iPSC differentiation. Clinical trials of NK cell-based therapies for treatment of multiple myeloma led by researchers at KI have yielded promising preliminary results with long-lasting remissions. In a very cross-knit collaboration between Sorrento and KI, the team will aim to establish novel allogeneic, off-the-shelf, retargeted NK cell-based therapies.

Utilizing iPSCs enables mass production of off-the-shelf NK cell therapies that leverage Sorrento’s existing manufacturing infrastructure and know-how. Sorrento expects these validated re-engineered NK cell-based therapeutic candidates could potentially become a new generation in off-the-shelf treatments for cancer and infectious diseases. The core research will be performed at Karolinska Institutet with active involvement of the Sorrento R&D team in San Diego.

"The present collaboration brings together key competence from Sorrento and KI in an important area of cancer immunotherapy research. Sorrento’s intellectual contribution to the research at the Competence Center is a critical piece in enabling retargeted off-the-shelf NK cell products," said Evren Alici, Principal Investigator at KI.

"This is an important step in further enabling academic and industrial partnerships in the mission of achieving common goals for advancement of novel cancer immunotherapies," said Hans-Gustaf Ljunggren, Director of the NextGenNK Competence Center.

On June 4, 2021 Notable Labs Inc., a leader in technology-powered life science with a proprietary platform for predicting patient outcomes and accelerating precision drug development, reported top-line results from its clinical response prediction technology platform in a pediatric acute myeloid leukemia (AML) study to be presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting to be held June 4th-8th (Press release, Notable Labs, JUN 4, 2021, View Source [SID1234583542]). The data will be presented by Dr. Alexandra Stevens at Texas Children’s Cancer Center and highlights the correlation of functional drug sensitivity screening using Notable’s predictive technology platform with clinical outcomes of pediatric patients.

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In the exploratory study, blood or bone marrow samples from 22 de novo pediatric AML patients prior to receiving pre-induction chemotherapy were processed using Notable’s predictive technology platform. Chemosensitivity profiles across a broad spectrum of ex vivo conditions were analyzed and integrated into a predictive measure for individual patients. This measure of ex vivo drug sensitivity correlated with the patients’ clinical results of minimal residual disease and one year relapse-free survival.

"Our collaboration with one of the leading pediatric medical centers further demonstrates the potential of Notable’s prediction technology in identifying and fast-tracking combination therapies in a real-world situation." said Dr. Thomas Bock, CEO of Notable. Dr. Stevens added, "These results are a critical step forward towards our vision of precision medicine where treatments are focused on those patients who will clinically respond, especially for hard-to-treat patient populations."

Details of the presentation are as follows:

Poster Presentation

Title: Ex Vivo Drug Sensitivity Assay Correlates with Clinical Response in Pediatric AML
Session Name: Poster Session: Pediatric Oncology
Abstract Number: 10032
Presentation Time: Available beginning June 4th, 2021