On April 16, 2023 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, autoimmune, metabolic, ophthalmology and other major diseases, reported that the final analysis results of ORIENT-15, the Phase 3 study evaluating sintilimab in combination with chemotherapy for the first-line treatment of esophageal squamous cell carcinoma (ESCC) were released in a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 (Abstract CT075) (Press release, Innovent Biologics, APR 16, 2023, View Source [SID1234630131]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

As of data cutoff date (August 28, 2022), a total of 690 patients were randomly assigned and received treatment, and the median follow-up was 32.2 months.

Sintilimab plus chemotherapy significantly improved the median overall survival (mOS) over placebo plus chemotherapy with a 33.9% reduction in risk of death (HR 0.661; P<0.0001) and a 4.6-month improvement in mOS (17.4 vs 12.8 months) in all randomized patients (the ITT population); and 36.5% reduction in risk of death (HR 0.635; P=0.0001) and a 3.9-month improvement in mOS (18.4 vs 14.5 months) in PD-L1 positive patients (defined as combined positive score [CPS] ≥10).

Estimated OS rates at 12 and 24 months for sintilimab plus chemotherapy versus chemotherapy alone in all randomized patients were 64.0% vs 53.5% and 41.4% vs 22.9%, respectively.

The safety profile of sintilimab in this study was consistent with that observed in previously reported studies of sintilimab, and no additional safety signals were identified for the combination of sintilimab and chemotherapy with approximate 16 months of extended follow-up.

The principal investigator of the ORIENT-15 study, Prof. Shen Lin from Peking University Cancer Hospital and Institute, stated, "More than half of new and fatal cases of esophageal cancer in the world occur in China every year. Esophageal cancer is the fifth most commonly diagnosed cancer and the fourth leading cause of death from cancer in China, and squamous cell carcinoma is the predominant histologic type[i]. The interim analysis of ORIENT-15 met all endpoints, and sintilimab in combination with chemotherapy has been approved by the NMPA to be a first-line treatment option for patients with advanced ESCC. In addition, this new indication of sintilimab has been included in the updated China National Reimbursement Drug List (NRDL), benefiting broader patient groups. In this final analysis, sintilimab in combination with chemotherapy demonstrated continued significant OS benefits, further supporting the use of sintilimab plus chemotherapy as a standard of care for first-line treatment in these patients."

Dr. Hui Zhou, Senior Vice President of Innovent, stated, "The approval of immunotherapy has significantly improved the clinical benefits of standard treatments in patients with advanced esophageal squamous cell carcinoma. According to the results of interim analysis, sintilimab plus chemotherapy has been approved by NMPA. We are also pleased that this indication of sintilimab has been included in the NRDL, making sintilimab the only PD-1 inhibitor for the first-line treatment of five high-incidence cancer types included in the NRDL. In this final analysis, the continued significant OS benefits have been verified in advanced ESCC patients with an acceptable safety profile over time, and further demonstrated that sintilimab as a first-line treatment option will benefit ESCC patients in China."

About the ORIENT-15 Study

ORIENT-15 is a global randomized, double-blind, multicenter Phase 3 clinical study evaluating sintilimab in combination with chemotherapy, compared to placebo in combination with chemotherapy, for the first-line treatment of unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma (ClinicalTrials.gov, NCT03748134). At the time of interim analysis, a total of 659 eligible patients (of the planned 676 estimated participants) were enrolled and randomly assigned into the experimental group or control group in a 1:1 ratio. The primary endpoints were overall survival (OS) in all randomized patients and OS in PD-L1 positive (defined as CPS ≥10) patients[ii].

About Esophageal Squamous Cell Carcinoma (ESCC)

Esophageal cancer (EC) is one of the most common malignant tumors worldwide that begins in the inner layer (mucosa) of the esophagus, which connects the throat to the stomach. Based on GLOBOCAN 2020 estimates, approximately 600,000 new cases of esophageal cancer are diagnosed and approximately 540,000 deaths result from the disease worldwide each year[iii]. Esophageal cancer is the seventh most commonly diagnosed cancer and the sixth leading cause of death from cancer worldwideiii. More than half of new and fatal cases of esophageal cancer in the world occur in Chinai. In China, it is estimated there were approximately 320,000 new cases of esophageal cancer diagnosed and approximately 300,000 deaths resulting from the disease in 2020i. Esophageal cancer is the fifth most commonly diagnosed cancer and the fourth leading cause of death from cancer in China, where it has a five-year survival rate of only 30%i.

The two main types of esophageal cancer are squamous cell carcinoma (SCC) and adenocarcinoma. In China, SCC is the predominant histologic type, accounting for more than 90% of all esophageal cancer[iv]. In the past, first-line standard systemic therapy was chemotherapy based on platinum drugs for unresectable locally advanced, recurrent or metastatic ESCC, which calls for more effective first-line treatment options. Several PD-1 inhibitors have been approved as first-line treatment in combination with chemotherapy[v]，[vi].

About Sintilimab

Sintilimab, marketed as TYVYT (sintilimab injection) in China, is a PD-1 immunoglobulin G4 monoclonal antibody co-developed by Innovent and Eli Lilly and Company. Sintilimab is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells[vii]. Innovent is currently conducting more than 20 clinical studies of sintilimab to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.

In China, sintilimab has been approved and included in the National Reimbursement Drug List (NRDL) for all six indications. The updated NRDL reimbursement scope of TYVYT (sintilimab injection) include:

For the treatment of unresectable locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma;
For the treatment of unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma;
For the treatment of unresectable locally advanced or metastatic non-squamous non-small cell lung cancer lacking EGFR or ALK driver gene mutations;
For the treatment of unresectable locally advanced or metastatic squamous non-small cell lung cancer;
For the treatment of unresectable or metastatic hepatocellular carcinoma with no prior systematic treatment;
For the treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy.
Innovent currently has the regulatory submission for sintilimab in combination with bevacizumab biosimilar and chemotherapy for EGFR-TKI failed EGFR-mutated non-squamous NSCLC under review in the China’s NMPA.

Additionally, two clinical studies of sintilimab have met their primary endpoints:

Phase 2 study of sintilimab monotherapy as second-line treatment of esophageal squamous cell carcinoma;
Phase 3 study of sintilimab monotherapy as second-line treatment for squamous NSCLC with disease progression following platinum-based chemotherapy.

On April 16, 2023 Abbisko (Stock Code: 2256.HK) reported the results of five latest preclinical studies at the 2023 American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting (Press release, Abbisko Therapeutics, APR 16, 2023, View Source [SID1234630130]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

These include its self-developed CSF-1R inhibitor Pimicotinib (ABSK021), which has been recognized as a breakthrough therapy in China and the United States, and ABSK112, a next-generation of EGFR Exon20 inhibitor that may become the best-in-class to overcome resistance mutations, and a next-generation of the latest preclinical and translational research progress of the FGFR4 inhibitor ABSK012 and FGFR inhibitor ABSK121 that overcome drug-resistant mutations, and the next-generation KRAS inhibitor ABSK071.

Abbisko presented the following posters at the AACR (Free AACR Whitepaper) Annual Meeting:

Medicine

Title

Abstract Number

ABSK021

A potent and selective small molecule inhibitor of CSF-1R ABSK021 demonstrates strong efficacy in preclinical models of osteosarcoma

LB329

ABSK112

Discovery and characterization of ABSK112, a next-generation and potential best-in-class EGFR Exon20 mutant inhibitor with superior selectivity and brain penetration ability

LB327

ABSK012

Discovery & characterization of a next-generation FGFR4 inhibitor overcoming resistant mutations

LB328

ABSK121

Discovery and characterization of a next-generation FGFR inhibitor overcoming FGFR resistant mutations

LB317

ABSK071

A next-generation KRASG12C inhibitor ABSK071 demonstrated broad synergy with other therapeutic agents in KRASG12C mutated cancer models

LB316

Title: A potent and selective small molecule inhibitor of CSF-1R ABSK021 demonstrates strong efficacy in preclinical models of osteosarcoma
Abstract Number: LB329
Research Background：
Osteosarcoma is the most common primary malignant bone tumor in children and young adults. Surgery combined with multimodal chemotherapy remains as the standard treatment for osteosarcoma patients. However, patients with osteosarcoma metastasis have a five-year survival rate of less than 30%, and their long-term outcomes have not improved over the last 30 years, representing a high unmet medical need. CSF-1/CSF-1R signaling is crucial for the survival, function, proliferation and differentiation of myeloid lineage cells, including osteoclasts and monocytes/macrophages. Targeting CSF-1R either on tumor cells or tumor-associated macrophages has been reported to limit osteosarcoma progression in preclinical models. ABSK021, an oral, highly potent and selective small molecule inhibitor of CSF-1R, showed significant anti-tumor activity and favorable safety profile in patients with advanced tenosynovial giant cell tumor in phase 1b trial. We demonstrated the treatment potential of ABSK021 for osteosarcoma patients through a series of preclinical in vitro and in vivo experiments, as well as human osteosarcoma profiling.
Result：
ABSK021 has strong inhibition of CSF-1R activity and corresponding anti-tumor activity in preclinical osteosarcoma models. High prevalence of CSF-1R expression was also found in osteosarcoma patients, suggesting great potential of utilizing ABSK021 as a novel therapy to treat osteosarcoma patients in clinic.

Title: ABSK112, a potential best-in-class EGFR exon 20 mutant Inhibitor with excellent selectivity and brain penetration
Abstract Number: LB327
Research Background：
EGFR Exon20 mutations are clinically validated oncogenic alterations including a wide spectrum of mutations occurring in lung cancer and various other cancer types. Although several EGFR Exon20 inhibitors have reached clinical stage or received approval, there still leave large room for improvement in safety and efficacy, likely due to their limited selectivity against wild-type EGFR or other kinases, suboptimal mutation coverage, and lack brain penetrating ability. Herein, we have discovered a novel and next-generation EGFR Exon20 mutation inhibitor, ABSK112. It showed high selectivity over wild-type EGFR and other kinases, as well as a more comprehensive coverage over majority of EGFR Exon20 mutations in comparison with other EGFR Exon20 inhibitors.
Result：
ABSK112 is a leading next-generation EGFR Exon20ins inhibitor with improved selectivity over wild-type EGFR and strong brain penetrating ability. It shows superior in vivo efficacy in various EGFR Exon20ins xenograft models, and broader spectrum of mutation coverage than clinical stage competitors.

Title: Discovery & characterization of a next-generation FGFR4 inhibitor overcoming resistant mutations
Abstract Number: LB328
Research Background：
Aberrant activation of FGF19-FGFR4 signaling pathway plays an essential role in the tumorigenesis of Hepatocellular carcinoma (HCC) and FGFR4 inhibitors have shown preliminary efficacy in recent clinical trials for patients with FGF19 overexpression. However, the observed responses only lasted a few months before tumors relapse. Acquired FGFR4 resistant mutations were found in ~30% of FGFR4 inhibitor responsive patients. Similar FGFR4 mutations haven also been found de novo in about 7-10% of Rhabdomyosarcoma (RMS) and ER-treated invasive lobular carcinoma patients. First generation FGFR4 inhibitors have minimal activity against these de novo or acquired resistant mutations. Therefore, next-generation of FGFR4 inhibitors are needed to overcome these resistant FGFR4 mutations to provide better treatment options for patients. Using advanced computation-aided structural analysis and medicinal chemistry design, we have discovered a next-generation small molecule FGFR4 inhibitor, ABSK012, and demonstrated its strong activities against de novo and acquired resistant FGFR4 mutations while retaining inhibition for wild-type FGFR4.
Result：
ABSK012, presented here by Abbisko Therapeutics, is a highly potent, selective, and next-generation small molecule FGFR4 inhibitor overcoming FGFR4 mutations resistant to first-generation inhibitors. Its superior preclinical profile supports its fast-track development into clinic.

Title: Discovery and characterization of a next-generation FGFR inhibitor overcoming FGFR resistant mutations
Abstract Number: LB317
Research Background：
FGFRs play important roles in cancer development and inhibition of FGFR could disrupt tumor cell proliferation and growth. Four selective FGFR inhibitors have been approved (erdafitinib, pemigatinib, infigratinib, and futibatinib) and several others are in clinical development. Unfortunately upon treatment with these first-generation FGFR inhibitors, acquired resistance often develops and is frequently associated with the emergence of secondary FGFR2/3 kinase domain mutations. Therefore, selectively targeting FGFR2/3 as well as their resistant mutations may render a second-generation treatment approach for the refractory/relapsed patients. Using advanced computation-aided structural analysis and medicinal chemistry design, we have discovered a novel, next-generation, and highly selective FGFR inhibitor, ABSK121. This novel inhibitor demonstrated robust anti-tumor activity in FGFR-dependent tumor models with strong activities against not only de novo but also acquired resistant mutations.
Result：
ABSK121, presented here by Abbisko Therapeutics, is a highly potent, selective, and next-generation small molecule FGFR inhibitor with great potency against resistant FGFR mutations. Its superior profile supports fast-track preclinical and clinical development.

Title: A next-generation KRASG12C inhibitor ABSK071 demonstrated broad synergy with other therapeutic agents in KRASG12C mutated cancer models
Abstract Number: LB316
Research Background：
KRAS is frequently mutated in human cancers, including pancreatic (~90%), colorectal (~35%), and lung cancer (~25%). The KRASG12C mutation (single amino acid substitution of cysteine for glycine at position 12) accounts for ~14% of lung cancer, ~4% of colorectal cancer, and ~2% of pancreatic cancer. Currently, two covalent KRASG12C inhibitors, namely sotorasib (AMG-510) and adagrasib (MRTX-849), have been approved as monotherapy to treat locally advanced or metastatic NSCLC with KRASG12C mutation through accelerated approval process.
Despite the beneficial effects of KRASG12C inhibitors in clinic for certain patients, the limited antitumor efficacy in most patients and potential drug resistance are major concerns. A next-generation inhibitor with better inhibitory activity may improve anti-tumor efficacy. Combination with other therapeutic agents may also improve the single-agent activity of KRASG12C inhibitors. These approaches could both overcome the limitations of sotorasib and adagrasib and provide additional benefits to patients.
Result：
ABSK071 is a next-generation KRASG12C inhibitor with greater activity and anti-tumor efficacy in vitro and in vivo. It also demonstrated broad synergistic effects with a large set of targeted agents and immuno-oncology agents, indicating its strong potential in combinatory therapy in treating a wider range of KRASG12C-dependent cancers.

On April 16, 2023 MorphoSys U.S. Inc., a fully owned subsidiary of MorphoSys AG (FSE: MOR; NASDAQ: MOR), and Incyte (Nasdaq: INCY) reported final five-year follow-up data from the Phase 2 L-MIND study showing that Monjuvi (tafasitamab-cxix) plus lenalidomide followed by Monjuvi monotherapy provided prolonged, durable responses in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (Press release, MorphoSys, APR 16, 2023, View Source [SID1234630127]). These data were featured as a late-breaking oral presentation (Abstract # CT022) at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 in Orlando, Florida.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Five-year data demonstrating durability of response is meaningful for oncologists as they consider the most appropriate treatment option for a patient," said Johannes Duell, M.D., University Hospital Würzburg Medical Clinic and Polyclinic. "The prolonged and durable responses seen at five years among relapsed or refractory DLBCL patients in the L-MIND study show that the Monjuvi treatment regimen may have curative potential, which I look forward to seeing explored in future studies."

At the data cut-off (Nov. 14, 2022) for the full analysis set (80 patients), the overall response rate (ORR) was 57.5% (95% CI = 45.9, 68.5), and a complete response (CR) was observed in 41.2% of patients (95% CI = 30.4, 51.6; n = 33). A partial response (PR) was observed in 16.2% of patients (95% CI = 8.9, 26.2; n =13). Additional results include:

Median duration of response was not reached after a median follow up of 44.0 months (95% CI = 29.9, 57.0).
The median overall survival was 33.5 months (95% CI = 18.3, NR) and median progression-free survival was 11.6 months (95% CI = 5.7, 45.7).
Of the 21 patients with >60 months of follow-up, 14 had received one prior line of therapy (pLoT), and seven patients had received ≥2 pLoT.
Patients with one pLoT (n = 40) had a higher ORR of 67.5% (CR = 52.5% and PR = 15%) compared to 47.5% of patients with two or more pLoT (n = 40; CR = 30% and PR = 17.5%)
No new safety signals were identified. The majority of adverse events (AEs) were grade 1 or grade 2 during both combination and monotherapy treatment. Patients experienced a lower frequency of all-grade and grade 3 or higher adverse events during monotherapy. The most common adverse events with combination therapy were neutropenia (incidence per person per year, all-grade/grade ≥3: 3.79/2.09) and thrombocytopenia (1.52/0.52), which declined after patients switched to monotherapy (all-grade/grade ≥3: 1.09/0.70 and 0.17/0.06, respectively, in the first two years of monotherapy). Neutropenia and diarrhea were the most common adverse events in the first two years of monotherapy.

"The totality of the long-term L-MIND data presented at AACR (Free AACR Whitepaper) further reinforce our confidence that the Monjuvi plus lenalidomide combination remains the in-practice, outpatient, targeted immunotherapy option that can provide sustained remissions for patients with relapsed or refractory DLBCL who are not eligible for autologous stem cell transplant," said Tim Demuth, M.D., Ph.D., Chief Research and Development Officer, MorphoSys. "The durable responses and consistent safety profile observed in the five-year analysis are encouraging and further support the use of the Monjuvi regimen as a potentially curative option for appropriate patients."

"The new five-year L-MIND data build on prior analyses that detail the potential for Monjuvi plus lenalidomide to provide long-term, meaningful responses for certain patients with relapsed or refractory DLBCL, a historically difficult-to-treat form of the disease," said Steven Stein, M.D., Chief Medical Officer, Incyte. "We look forward to continuing to explore the potential of Monjuvi to help patients with newly diagnosed DLBCL, as well as other CD19-expressing lymphomas."

In July 2020, the U.S. Food and Drug Administration (FDA) approved Monjuvi 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. Monjuvi, in combination with lenalidomide, was granted accelerated approval based on the one-year primary analysis of the L-MIND study. The data for the five-year analysis of the L-MIND study have not yet been submitted to, or reviewed by, the FDA.

About Diffuse Large B-cell Lymphoma (DLBCL)

DLBCL is the most common type of non-Hodgkin lymphoma in adults worldwide1, 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 thereafter2, leading to a high medical need for new, effective therapies2, especially for patients who are not eligible for an autologous stem cell transplant in this setting.

About L-MIND

The L-MIND trial was 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 who had at least one, but no more than three, prior lines of therapy, including an anti-CD20 targeting therapy (e.g., rituximab), who were not eligible for high-dose chemotherapy or refused subsequent autologous stem cell transplant. The study’s primary endpoint was overall response rate. Secondary outcome measures included duration of response, progression-free survival and overall survival. In May 2019, the study reached its primary completion. For more information about L-MIND, visit View Source

About Monjuvi (tafasitamab-cxix)

Tafasitamab is a humanized Fc-modified CD19 targeting immunotherapy. In 2010, MorphoSys licensed exclusive worldwide rights to develop and commercialize tafasitamab from Xencor, Inc. Tafasitamab incorporates an XmAb 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).

In the United States, Monjuvi (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 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 Europe, Minjuvi (tafasitamab) received conditional marketing authorization in combination with lenalidomide, followed by Minjuvi monotherapy, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplant (ASCT).

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

Monjuvi and Minjuvi are registered trademarks of MorphoSys AG. Tafasitamab is co-marketed by Incyte and MorphoSys under the brand name Monjuvi in the U.S., and marketed by Incyte under the brand name Minjuvi in Europe and Canada.

XmAb 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-related 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.

Please see the full Prescribing Information for Monjuvi, including Patient Information, for additional Important Safety Information.

On April 16, 2023 Affimed N.V. (Nasdaq: AFMD) ("Affimed", or the "Company"), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported the final results from its phase 2 REDIRECT study investigating its innate cell engager (ICE) AFM13 monotherapy in patients with heavily pretreated advanced-stage r/r PTCL (Press release, Affimed, APR 16, 2023, View Source [SID1234630126]). The results are being presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting by Dr. Won Seog Kim, Professor of Hematology-Oncology at Samsung Medical Center in Seoul and a principal investigator for the study, and establishes that AFM13 monotherapy showed efficacy in the treatment of relapsed/refractory peripheral T cell lymphoma (r/r PTCL) patients with a differentiated safety profile.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Primary efficacy measures include an ORR of 32.4% and a CR rate of 10.2%. Key secondary and exploratory outcome measures include safety, durability of response, progression free survival and overall survival.

Median DoR was 2.3 months, median PFS was 3.5 months and median OS was 13.8 months. PFS and OS were comparable with currently approved therapies for r/r PTCL. Of all PTCL subsets, patients with AITL exhibited the highest ORR (53.3%) and CR (26.7%) with DoR not meaningfully different across the various subsets.

The safety profile of AFM13 was well managed and consistent with previously reported data of prior and ongoing clinical studies with AFM13. Most common TEAEs were IRR (25%), neutropenia (10.2%) and pyrexia (8.3%). No AFM13-related fatal toxicities were observed.

"I’m very proud of the REDIRECT results demonstrating that innate immune cell engagement through our ICE AFM13 has effective single agent activity with a differentiated safety profile. These data substantiate the next step towards further development of AFM13 in PTCL" said Dr. Adi Hoess, Chief Executive Officer at Affimed. "Our parallel study investigating AFM13 in combination with allogeneic NK cells shows that such a combination can achieve remarkable clinical outcomes for patients with CD30-positive lymphomas. We believe we can build on the already meaningful activity through the combination with Artiva’s NK Cell (AB-101) giving these vastly underserved patients a meaningful treatment option."

"The strong activity of AFM13 in heavily pretreated patients with peripheral T cell Lymphoma is very encouraging and, coupled with the favorable safety profile, provides a rationale for further clinical development of the agent in PTCL. PTCL is a disease that can be challenging to treat with an urgent need for new mechanisms, as there are very few options today. AFM13 holds promise to address the gap in current treatment options," said Dr. Won Seog Kim.

About REDIRECT
REDIRECT is a registration-directed phase 2 open-label, multicenter, global study investigating the efficacy and safety of AFM13 monotherapy in patients with CD30-positive r/r PTCL. The primary outcome measure was the objective response rate (ORR) following treatment with AFM13 as measured by an independent review committee (IRC) by FDG-PET. Secondary and exploratory outcome measures included DoR, PFS, OS, the safety of AFM13 as well as pharmacokinetics and immunogenicity of AFM13. In the trial, 108 patients received treatment with AFM13 as weekly intravenous infusions of 200 mg for the duration of the trial participation. Disease assessment was conducted at screenings every 8 weeks for the first 2 assessments and every 12 weeks thereafter.

About Peripheral T cell Lymphomas
Peripheral T cell lymphomas are highly aggressive and one of the most difficult to treat forms of lymphoma with very poor prognosis for patients, especially in later lines of therapy. Based on the compelling data seen in Hodgkin lymphoma for the combination of AFM13 with cord blood-derived NK cells in the AFM13-104 study, the Company believes that the combination with NK cells has a higher probability to deliver increased anti-tumor activity and a more durable clinical benefit to address the unmet need in this patient population. Accordingly, Affimed will focus investment on clinical development in the combination of AFM13 with Artiva’s AB-101 NK cell product and does not intend to pursue an accelerated approval for AFM13 monotherapy in PTCL.

Details of the oral presentation are as follows:

Title: A phase 2 study of AFM13 in patients with CD30-positive relapsed or refractory (R/R) peripheral T cell lymphoma (PTCL)
Session: Novel Clinical Trials for Hematological Malignancies
Presentation Date & Time: Sunday April 16, 3:00 – 5:00 p.m. EDT
Location: Orange County Convention Center, Orlando, Florida, Valencia A

The presentation/abstract is accessible through the following link: View Source

About AFM13
AFM13 is a first-in-class innate cell engager (ICE) that uniquely activates the innate immune system to destroy CD30-positive hematologic tumors. AFM13 induces specific and selective killing of CD30-positive tumor cells, leveraging the power of the innate immune system by engaging and activating natural killer (NK) cells and macrophages. AFM13 is Affimed’s most advanced ICE clinical program and is currently being evaluated as monotherapy in a registration-directed trial in patients with relapsed/refractory peripheral T cell lymphoma (REDIRECT). Additional details can be found at www.clinicaltrials.gov (NCT04101331). The study achieved an ORR of 32.4% demonstrating anti-tumor activity with a DOR of 2.3 months and a well-managed safety profile. AFM13 is a tetravalent bispecific innate cell engager designed to act as a bridge between the innate immune cells and the tumor creating the necessary proximity for the innate immune cells to specifically destroy the tumor cells.

On April 16, 2023 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported new data from the Phase III IMbrave050 study that show Tecentriq (atezolizumab) plus Avastin (bevacizumab) demonstrated a statistically significant improvement in recurrence-free survival (RFS) in people with hepatocellular carcinoma (HCC) at high risk of disease recurrence following liver resection or ablation with curative intent (Press release, Genentech, APR 16, 2023, View Source [SID1234630125]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Four out of five people with HCC who receive surgery with curative intent may still see their cancer return. Thus, an urgent need exists for adjuvant treatments to prevent early recurrence and improve survival rates," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "With Tecentriq plus Avastin already a standard of care in unresectable HCC, we are pleased with the potential of these results and look forward to seeing more mature data."

The Tecentriq investigational combination reduced the risk of cancer returning by 28%, compared with active surveillance, at a median follow-up of 17.4 months (independent review facility [IRF]-RFS hazard ratio [HR]=0.72, 95% CI: 0.56-0.93; P=0.0120). The IRF-RFS findings were generally consistent across clinical subgroups. Overall survival (OS), a key secondary endpoint, was immature (7% event-rate) at the time of data analysis. The safety data for Tecentriq plus Avastin were consistent with the well-established safety profile of each therapeutic treatment and with the underlying disease.

The late-breaking data will be presented at the AACR (Free AACR Whitepaper) Annual Meeting 2023 and have been included as part of the official press program. Discussions with health authorities are ongoing and follow-up will continue for the final RFS data and more mature OS data at the next planned analysis.

The IMbrave050 study is part of Genentech’s overall commitment to drive fundamental treatment change and improve outcomes for people living with liver cancer. Tecentriq plus Avastin was the first treatment in over a decade to significantly improve OS over the existing standard of care, based on data from the IMbrave150 study. The Tecentriq combination quickly became a standard of care in unresectable HCC and is clearly defined as a preferred front-line treatment in multiple international clinical guidelines.

Genentech has an extensive development program for Tecentriq, including multiple ongoing and planned Phase III studies across different lung, genitourinary, skin, breast, gastrointestinal, gynecological, and head and neck cancers. This includes studies evaluating Tecentriq both alone and in combination with other medicines, as well as studies in metastatic, adjuvant and neoadjuvant settings across various tumor types. In addition, Genentech has developed a subcutaneous formulation of Tecentriq, which is currently under review by health authorities globally.

About the IMbrave050 study

IMbrave050 is a Phase III global, multicenter, open-label, randomized study evaluating the efficacy and safety of adjuvant Tecentriq plus Avastin, compared with active surveillance, in people with HCC at high risk of recurrence (determined by the size and number of cancerous lesions and the histopathology results, if available) after surgical resection or ablation with curative intent.

The study randomized 668 people with a ratio of 1:1 to receive either Tecentriq (1,200 mg every three weeks) plus Avastin (15 mg/kg every three weeks) for a period of 12 months or 17 cycles, or no intervention with active surveillance. The primary endpoint is independent review facility-assessed RFS. Key secondary endpoints include OS, RFS as determined by the investigator and RFS in patients with PD-L1-positive disease.

About hepatocellular carcinoma

Liver cancer is the third leading cause of cancer death and one of the few cancers where mortality is rising. It is estimated that nearly 42,000 Americans were diagnosed with liver cancer in 2022. Nine out of ten cases of HCC are caused by chronic liver disease, which includes chronic hepatitis B and C infection, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcohol-related liver disease (ALD) and cirrhosis resulting from these conditions.

If diagnosed in the early stage, surgery may be prescribed to remove the primary tumor, however an estimated 70-80% of people with early-stage HCC experience disease recurrence following surgery. Early recurrence is associated with poorer prognosis and shorter survival. Tumor size, number of tumors, and portal vein invasion are associated with an increased risk of recurrence.

About Tecentriq (atezolizumab)

Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1. Tecentriq is designed to bind to PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the re-activation of T cells. Tecentriq may also affect normal cells.

About Avastin (bevacizumab)

Avastin is a prescription-only medicine that is a solution for intravenous infusion. It is a biologic antibody designed to specifically bind to a protein called VEGF that plays an important role throughout the lifecycle of the tumor to develop and maintain blood vessels, a process known as angiogenesis. Avastin is designed to interfere with the tumor blood supply by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells. The tumor blood supply is thought to be critical to a tumor’s ability to grow and spread in the body (metastasize).

Tecentriq U.S. Indications

Tecentriq is a prescription medicine used to treat:

Adults with a type of lung cancer called non-small cell lung cancer (NSCLC).

Tecentriq may be used alone as a treatment for their lung cancer:
to help prevent their lung cancer from coming back after their tumor(s) has been removed by surgery and they have received platinum-based chemotherapy, and
they have stage 2 to 3A NSCLC (patients should talk to their healthcare provider about what these stages mean), and
their cancer tests positive for "PD-L1."
Tecentriq may be used alone as their first treatment when their lung cancer:
has spread or grown, and
their cancer tests positive for "high PD-L1," and
their tumor does not have an abnormal "EGFR" or "ALK" gene.
Tecentriq may be used with the medicines bevacizumab, paclitaxel, and carboplatin as their first treatment when their lung cancer:
has spread or grown, and
is a type called "non-squamous NSCLC," and
their tumor does not have an abnormal "EGFR" or "ALK" gene.
Tecentriq may be used with the medicines paclitaxel protein-bound and carboplatin as their first treatment when their lung cancer:
has spread or grown, and
is a type called "non-squamous NSCLC," and
their tumor does not have an abnormal "EGFR" or "ALK" gene.
Tecentriq may be used alone when their lung cancer:
has spread or grown, and
if they have tried chemotherapy that contains platinum, and it did not work or is no longer working.
if their tumor has an abnormal "EGFR" or "ALK" gene, they should have also tried an FDA-approved therapy for tumors with these abnormal genes, and it did not work or is no longer working.
Adults with a type of lung cancer called small cell lung cancer (SCLC). Tecentriq may be used with the chemotherapy medicines carboplatin and etoposide as their first treatment when their lung cancer:

is a type called "extensive-stage small cell lung cancer," which means that it has spread or grown.
Adults with a type of liver cancer called hepatocellular carcinoma (HCC). Tecentriq may be used with the medicine bevacizumab when their liver cancer:

has spread or cannot be removed by surgery, and
they have not received other medicines by mouth or injection through their vein (IV) to treat their cancer.
Adults with a type of skin cancer called melanoma. Tecentriq may be used with the medicines cobimetinib and vemurafenib in patients with melanoma when their skin cancer:

has spread to other parts of the body or cannot be removed by surgery, and
has a certain type of abnormal "BRAF" gene. Healthcare providers will perform a test to make sure this Tecentriq combination is right for the patient.
Adults and children 2 years of age and older with a type of soft tissue tumor (cancer) called alveolar soft part sarcoma (ASPS). Tecentriq may be used when their sarcoma:

has spread to other parts of the body or cannot be removed by surgery.
It is not known if Tecentriq is safe and effective when used:

in children younger than 2 years of age for the treatment of ASPS.
in children for the treatment of NSCLC, SCLC, HCC or melanoma.
Important Safety Information

What is the most important information about Tecentriq?

Tecentriq can cause the immune system to attack normal organs and tissues in any area of the body and can affect the way they work. These problems can sometimes become severe or life threatening and can lead to death. Patients can have more than one of these problems at the same time. These problems may happen anytime during their treatment or even after their treatment has ended.

Patients should call or see their healthcare provider right away if they develop any new or worse signs or symptoms, including:

Lung problems

cough
shortness of breath
chest pain
Intestinal problems

diarrhea (loose stools) or more frequent bowel movements than usual
stools that are black, tarry, sticky, or have blood or mucus
severe stomach-area (abdomen) pain or tenderness
Liver problems

yellowing of the skin or the whites of the eyes
severe nausea or vomiting
pain on the right side of their stomach area (abdomen)
dark urine (tea colored)
bleeding or bruising more easily than normal
Hormone gland problems

headaches that will not go away or unusual headaches
eye sensitivity to light
eye problems
rapid heartbeat
increased sweating
extreme tiredness
weight gain or weight loss
feeling more hungry or thirsty than usual
urinating more often than usual
hair loss
feeling cold
constipation
their voice gets deeper
dizziness or fainting
changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness
Kidney problems

decrease in their amount of urine
blood in their urine
swelling of their ankles
loss of appetite
Skin problems

rash
itching
skin blistering or peeling
painful sores or ulcers in mouth or nose, throat, or genital area
fever or flu-like symptoms
swollen lymph nodes
Problems can also happen in other organs.

These are not all of the signs and symptoms of immune system problems that can happen with Tecentriq. Patients should call or see their healthcare provider right away for any new or worse signs or symptoms, including:

Chest pain, irregular heartbeat, shortness of breath, or swelling of ankles
Confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs
Double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight
Persistent or severe muscle pain or weakness, muscle cramps
Low red blood cells, bruising
Infusion reactions that can sometimes be severe or life-threatening. Signs and symptoms of infusion reactions may include:

chills or shaking
itching or rash
flushing
shortness of breath or wheezing
dizziness
feeling like passing out
fever
back or neck pain
Complications, including graft-versus-host disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if patients undergo transplantation either before or after being treated with Tecentriq. A healthcare provider will monitor for these complications.

Getting medical treatment right away may help keep these problems from becoming more serious. A healthcare provider will check patients for these problems during their treatment with Tecentriq. A healthcare provider may treat patients with corticosteroid or hormone replacement medicines. A healthcare provider may also need to delay or completely stop treatment with Tecentriq if patients have severe side effects.

Before receiving Tecentriq, patients should tell their healthcare provider about all of their medical conditions, including if they:

have immune system problems such as Crohn’s disease, ulcerative colitis, or lupus
have received an organ transplant
have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic)
have received radiation treatment to their chest area
have a condition that affects their nervous system, such as myasthenia gravis or Guillain-Barré syndrome
are pregnant or plan to become pregnant. Tecentriq can harm an unborn baby. Patients should tell their healthcare provider right away if they become pregnant or think they may be pregnant during treatment with Tecentriq. Females who are able to become pregnant:
A healthcare provider should do a pregnancy test before they start treatment with Tecentriq
They should use an effective method of birth control during their treatment and for at least 5 months after the last dose of Tecentriq
are breastfeeding or plan to breastfeed. It is not known if Tecentriq passes into the breast milk. Patients should not breastfeed during treatment and for at least 5 months after the last dose of Tecentriq

Patients should tell their healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of Tecentriq when used alone include:

feeling tired or weak
decreased appetite
nausea
cough
shortness of breath
The most common side effects of Tecentriq when used in lung cancer with other anti-cancer medicines include:

feeling tired or weak
nausea
hair loss
constipation
diarrhea
decreased appetite
The most common side effects of Tecentriq when used in hepatocellular carcinoma (HCC) with bevacizumab include:

high blood pressure
feeling tired or weak
too much protein in the urine
The most common side effects of Tecentriq when used in melanoma with cobimetinib and vemurafenib include:

skin rash
joint, muscle, or bone pain
feeling tired or weak
liver injury
fever
nausea
itching
swelling of legs or arms
mouth swelling (sometimes with sores)
low thyroid hormone levels
sunburn or sun sensitivity

Tecentriq may cause fertility problems in females, which may affect the ability to have children. Patients should talk to their healthcare provider if they have concerns about fertility.

These are not all the possible side effects of Tecentriq. Patients should ask their healthcare provider or pharmacist for more information about the benefits and side effects of Tecentriq.

Report side effects to the FDA at 1-800-FDA-1088 or View Source

Report side effects to Genentech at 1-888-835-2555.

Please see View Source for full Prescribing Information and additional Important Safety Information.

Avastin is approved for:

Avastin, in combination with atezolizumab, is indicated for the treatment of patients with unresectable or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy.

Possible serious side effects

Everyone reacts differently to Avastin therapy. So, it’s important to know what the side effects are. Although some people may have a life-threatening side effect, most do not. Their doctor will stop treatment if any serious side effects occur. Patients should contact their health care team if there are any signs of these side effects.

GI perforation. A hole that develops in the stomach or intestine. Symptoms include pain in the abdomen, nausea, vomiting, constipation, or fever
Abnormal passage in the body. This type of passage—known as a fistula—is an irregular connection from one part of the body to another and can sometimes be fatal
Wounds that don’t heal. A cut made during surgery can be slow to heal or may not fully heal. Avastin should not be used for at least 28 days before or after surgery and until surgical wounds are fully healed
Serious bleeding. This includes vomiting or coughing up blood; bleeding in the stomach, brain, or spinal cord; nosebleeds; and vaginal bleeding. If a patient has recently coughed up blood or had serious bleeding, they should be sure to tell their doctor
Severe high blood pressure. Blood pressure that severely spikes or shows signs of affecting the brain. Blood pressure should be monitored every 2 to 3 weeks while on Avastin and after stopping treatment
Kidney problems. These may be caused by too much protein in the urine and can sometimes be fatal
Infusion-related reactions. These were uncommon with the first dose (less than 3% of patients). 0.2% of patients had severe reactions. Infusion reactions include high blood pressure or severe high blood pressure that may lead to stroke, trouble breathing, decreased oxygen in red blood cells, a serious allergic reaction, chest pain, headache, tremors, and excessive sweating. The patient’s doctor or nurse will monitor for signs of infusion reactions
Severe stroke or heart problems. These may include blood clots, mini-stroke, heart attack, chest pain, and the heart may become too weak to pump blood to other parts of the body (congestive heart failure). These can sometimes be fatal
Nervous system and vision problems. Signs include headache, seizure, high blood pressure, sluggishness, confusion, and blindness
Side effects seen most often

In clinical studies across different types of cancer, some patients experienced the following side effects:

High blood pressure
Too much protein in the urine
Nosebleeds
Rectal bleeding
Back pain
Headache
Taste change
Dry skin
Inflammation of the skin
Inflammation of the nose
Watery eyes
Avastin is not for everyone

Patients should talk to their doctor if they are:

Undergoing surgery. Avastin should not be used for 28 days before or after surgery and until surgical wounds are fully healed
Pregnant or think they are pregnant. Data have shown that Avastin may harm a woman’s unborn baby. Birth control should be used while patients are on Avastin. If Avastin is stopped, patients should keep using birth control for 6 months before trying to become pregnant
Planning to become pregnant. Taking Avastin could cause a woman’s ovaries to stop working and may impair her ability to have children
Breastfeeding. Breastfeeding while on Avastin may harm the baby, therefore women should not breastfeed during and for 6 months after taking Avastin

Patients should talk with their doctor if they have any questions about their condition or treatment.

Report side effects to the FDA at 1-800-FDA-1088 or View Source Report side effects to Genentech at 1-888-835-2555.

For full Prescribing Information and Boxed WARNINGS on Avastin please visit View Source

About Genentech in cancer immunotherapy

Genentech has been developing medicines to redefine treatment in oncology for more than 35 years, and today, realizing the full potential of cancer immunotherapy is a major area of focus. With more than 20 immunotherapy molecules in development, Genentech is investigating the potential benefits of immunotherapy alone, and in combination with various chemotherapies, targeted therapies and other immunotherapies with the goal of providing each person with a treatment tailored to harness their own unique immune system.

In addition to Genentech’s approved PD-L1 checkpoint inhibitor, the company’s broad cancer immunotherapy pipeline includes other checkpoint inhibitors, individualized neoantigen therapies and T cell bispecific antibodies. For more information visit View Source