On September 20, 2021 GT Biopharma, Inc. (the "Company") (NASDAQ: GTBP), a clinical stage immuno-oncology company focused on developing innovative therapeutics based on the Company’s proprietary natural killer (NK) cell engager, TriKE platform, reported Dr. Jeffrey Miller’s mini-oral presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2021 (Press release, GT Biopharma, SEP 20, 2021, View Source [SID1234588066]). Jeffrey Miller, MD is a Professor of Medicine, University of Minnesota Medical School, Division of Hematology, Oncology and Transplantation and GT Biopharma’s consulting Chief Scientific Officer.

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!

The presentation at ESM0 highlighted the activity of camelid TriKEs in preclinical B7H3 positive and HER2+ solid tumor cancer models. GT Biopharma plans to advance these TriKEs into the clinic in 2022. The abstract is currently available on the ESMO (Free ESMO Whitepaper) website at www.esmo.org.

In addition to the ESMO (Free ESMO Whitepaper) presentation, GT Biopharma provided an update on its ongoing Phase 1 safety and feasibility clinical trial with GTB-3550. A total of 12 relapsed/refractory acute myelogenous leukemia (AML) and high grade myelodysplastic syndromes (MDS) patients have now been administered one cycle of GTB-3550, the company’s first-generation TriKE which targets CD33 on the surface of the leukemic cells in patients with AML and MDS.

The three most recent patients (numbers 10-12) have all tolerated the treatment well. One patient at the 150 mcg/kg/day dose experienced a mild Grade 1 cytokine release syndrome (CRS) event (fever), which was not dose limiting. Immune monitoring on these three most recent patients was consistent with the data previously reported on the first nine patients, and demonstrated activation, proliferation, and persistence of CD16 positive NK cells. Patient 11 had a bi-phenotypic leukemia which co-expressed both CD19 (a lymphoid marker) and CD33 (the myeloid marker which is targeted by GTB-3550); this patient showed a 50% reduction in CD33-positive leukemic cells (blasts), evidence of anti-leukemic activity of GTB-3550. Patients 10 and 12 did not experience blast cell reduction. The Company has previously reported that three of the first nine patients experienced a reduction in blast cells.

Gregory Berk, MD, President of R&D and Chief Medical Officer of GT Biopharma commented "We are very pleased with what we have learned from the Phase 1 GTB-3550 clinical trial. The TriKE is safe and well tolerated. The TriKE results in NK cell activation, proliferation, and persistence. There are also early signs of anti-leukemic activity. We are excited to advance GT Biopharma’s next generation camelid program for this difficult-to-treat patient population."

About Camelid Antibodies

Camelid antibodies are single domain antibodies (sdAbs) from the Camelidae family of mammals that include llamas, camels, and alpacas. These animals produce 2 main types of antibodies. One type of antibody camelids produce is the conventional antibody that is made up of 2 heavy chains and 2 light chains. They also produce another type of antibody that is made up of only 2 heavy chains and no light chain. This is known as heavy chain IgG (hcIgG). While these antibodies do not contain the CH1 region, they retain an antigen binding domain called the VHH region. VHH antibodies, also known as single domain antibodies, contain only the VHH region from the camelid antibody. Camelid antibodies have key characteristics, which include high affinity and specificity (equivalent to conventional antibodies), high thermostability, good solubility and strictly monomeric behavior, small size, relatively low production cost, ease of genetic engineering, format flexibility or modularity, low immunogenicity, and a higher penetration rate into tissues.

On September 20, 2021 Pyxis Oncology reported that it is aiming to close out a transformative 2021 with an IPO (Press release, Pyxis Oncology, SEP 20, 2021, View Source [SID1234590055]). Having licensed a pair of antibody-drug conjugates (ADCs) from Pfizer and raised a megaround to develop them, Pyxis is now seeking to tap public investors for cash in an IPO filing that sets the initial fundraising target at $100 million.

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!

Boston-based Pyxis will use the money to take three candidates into the clinic. PYX-201 and PYX-202 are leading the charge, with Pyxis expecting to file INDs for both prospects around the middle of next year. PYX-201, one of the assets picked up from Pfizer, is designed to hit EDB, which regulates blood vessels and is overexpressed in cancers of the lung, breast and other organs. Pyxis is initially targeting non-small cell lung cancer and breast cancer and sees scope to pair the drug with a checkpoint inhibitor.

PYX-202, which Pyxis licensed from LegoChem, hits DLK1, a transmembrane protein that is expressed in embryonic tissues—and re-expressed in some solid tumors—but highly restricted in healthy adult tissues. Pyxis has preclinical data in small cell lung cancer.

The third prospect, PYX-203, is following closely behind, with an IND penciled in for 2023. PYX-203, another of the Pfizer candidates, targets the CD123 antigen expressed in acute myeloid leukemia. Pyxis recently hired Jay Feingold, M.D., Ph.D., formerly of ADC Therapeutics, to lead the push into the clinic.

RELATED: Pyxis debuts next-gen cancer ADCs from under Pfizer’s wing

All of the targets are being pursued by other companies including ImmunoGen, MacroGenics and Philogen. Still more companies are working on ADCs and other modalities targeting the same cancers as those pursued by Pyxis.

Pyxis’ belief it can stand out from the competition is underpinned by potential differentiators such as the FACT platform that is behind two of its leading drug candidates. Pfizer identified the potential for site-specific conjugation techniques to boost the consistency of drug loading. Armed with the fruits of Pfizer’s work, Pyxis expects to improve efficacy and reduce systemic toxicity.

Pfizer let Pyxis have two preclinical candidates based on the platform for $5 million upfront and $20 million in stock, putting the Big Pharma just above Bayer at the top of the list of the biotech’s principal stockholders. Pyxis is on the hook for up to $660 million in milestones covering the first four licensed ADCs, and Pfizer will pocket more upfront fees if targets are added to the deal. Pyxis paid LegoChem an upfront fee of $500,000 in 2020 and $9 million in 2021 in relation to PYX-202.

On September 20, 2021 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM: HCM; HKEX: 13) reported that it has initiated SURTORI-01, a Phase III study to evaluate the efficacy and safety of surufatinib (SULANDA in China) in combination with toripalimab compared with FOLFIRI to treat patients with advanced neuroendocrine carcinoma ("NEC") who have progression of disease or intolerable toxicity after previous first-line chemotherapy (Press release, Hutchison China MediTech, SEP 20, 2021, View Source [SID1234590201]). The first patient was dosed on September 18, 2021 in China. Toripalimab is marketed as TUOYI in China by Shanghai Junshi Biosciences Co., Ltd. ("Junshi Biosciences").

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!

Professor Shen Lin, the lead principal investigator of the study and Vice President of Peking University Hospital and Cancer Institute, said: "There is a large unmet clinical need for patients with NEC, many of whom have a bleak prognosis. Following the encouraging preliminary data from the Phase II trial, we are excited to move into the next stage of development in combining the novel, oral angio-immuno kinase inhibitor surufatinib with the anti-PD-1 antibody toripalimab. We look forward to further testing the synergistic anti-tumor effects of this combination that could benefit NEC patients who have limited treatment options."

At the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Annual Meeting, encouraging preliminary data from the Phase II trial were disclosed for the surufatinib and toripalimab combination1. For the 20 patients in the NEC cohort as of December 31, 2020, who received an average of 5 cycles of treatments and are efficacy evaluable, objective response rate ("ORR") was 20% and disease control rate ("DCR") was 70%. Median progression-free survival ("PFS") was 3.9 months (95% CI: 1.3 – not reached). Grade 3 or higher treatment-related adverse events occurred in 33% of patients. Treatment related adverse events ("TRAEs") were manageable, with surufatinib or toripalimab interruption occurred in 6 (28.6%) and 4 (19%) patients respectively. There were neither serious adverse events ("AEs") nor AEs inducing treatment discontinuations or deaths. Updated data will be presented at the Chinese Society of Clinical Oncology (CSCO) 2021 Annual Meeting in late September.

The SURTORI-01 Phase III study is a randomized, controlled, open-label, multi-center study where approximately 200 patients are expected to be enrolled. For the study group, all patients will receive study treatment in 21-day cycle and the treatment will continue until there is a progression of disease, death, intolerable toxicity, or the end of study treatment (as other criteria specified in the protocol are met), whichever occurs first. The primary outcome measure is OS. The secondary outcome measures include PFS, ORR, duration of response (DoR), and DCR. Additional details may be found at clinicaltrials.gov, using identifier NCT05015621.

HUTCHMED is the sponsor of SURTORI-01 and responsible for all clinical and regulatory execution of the Phase III study. HUTCHMED and Junshi Biosciences are jointly funding the study.

Surufatinib is marketed in China under the brand name SULANDA for treating advanced neuroendocrine tumors ("NETs").

About NEC

Neuroendocrine neoplasms ("NEN") occur almost everywhere in the body but are most common in the gastrointestinal tract, pancreas, and lungs. NEC is one of the two common phenotypes of NEN. NECs are poorly differentiated, highly proliferating NENs, while NETs are well-differentiated, low-proliferating NENs. NECs are aggressive, fast-growing neoplasms that usually fail to express hormones or produce hormonal syndromes, and are not associated with hereditary tumor diseases.2

About Surufatinib

Surufatinib is a novel, oral angio-immuno kinase inhibitor that selectively inhibits the tyrosine kinase activity associated with vascular endothelial growth factor receptors (VEGFR) and fibroblast growth factor receptor (FGFR), which both inhibit angiogenesis, and colony stimulating factor-1 receptor (CSF-1R), which regulates tumor-associated macrophages, promoting the body’s immune response against tumor cells. Its unique dual mechanism of action may be very suitable for possible combinations with other immunotherapies, where there may be synergistic anti-tumor effects.

HUTCHMED currently retains all rights to surufatinib worldwide.

About Surufatinib Development

Extra-pancreatic NETs ("epNETs") in China: On December 29, 2020, surufatinib was granted drug registration approval by the National Medical Products Administration of China ("NMPA") for the treatment of epNET. Surufatinib is marketed in China under the brand name SULANDA. The approval was based on results from the SANET-ep study, a Phase III trial (clinicaltrials.gov identifier: NCT02588170) in patients with advanced epNETs conducted in China. The study met the pre-defined primary endpoint of PFS at a preplanned interim analysis, and was published in The Lancet Oncology3. Median PFS was significantly longer for patients treated with surufatinib at 9.2 months, compared to 3.8 months for patients in the placebo group (HR 0.334; 95% CI: 0.223-0.499; p<0.0001). Surufatinib had an acceptable safety profile, with the most common treatment related adverse events of grade 3 or worse being hypertension (36% of surufatinib patients vs. 13% of placebo patients), proteinuria (19% vs. 0%) and anemia (5% vs. 3%).

Pancreatic NETs ("pNETs") in China: On June 16, 2021, surufatinib was granted drug registration approval by the NMPA for the treatment of pNET. The approval was based on results from the SANET-p study, a Phase III trial (clinicaltrials.gov identifier: NCT02589821) in patients with advanced pNET in China. The pre-defined primary endpoint of PFS was met at a preplanned interim analysis and was published in The Lancet Oncology4, demonstrating that surufatinib reduces the risk of disease progression or death by 51% in patients, with a median PFS of 10.9 months compared to 3.7 months on placebo (HR 0.491; 95% CI: 0.391-0.755; p=0.0011). The safety profile of surufatinib was manageable and consistent with observations in prior studies.

Immunotherapy combinations: HUTCHMED entered into collaboration agreements to evaluate the safety, tolerability and efficacy of surufatinib in combination with anti-PD-1 monoclonal antibodies, including with tislelizumab (BGB-A317), TUOYI (toripalimab) and TYVYT (sintilimab), which are approved as monotherapies in China.

NETs in the U.S. and Europe: A U.S. Food and Drug Administration ("FDA") New Drug Application ("NDA") submission was accepted in June 2021, followed by a Marketing Authorisation Application ("MAA") submission to the European Medicines Agency ("EMA") validated in July 2021. The basis to support these filings includes the completed SANET-ep and SANET-p studies, along with existing data from surufatinib in U.S. epNET and pNET patients (clinicaltrials.gov identifier: NCT02549937). In the U.S., surufatinib was granted Fast Track Designations for development in pNET and epNET in April 2020, and Orphan Drug Designation for pNET in November 2019.

HUTCHMED has initiated an Expanded Access Protocol (EAP) in the U.S. to ensure patients with NET with limited therapeutic options have access to this treatment. Regulatory clearance of this protocol has been granted by the FDA and this program is open for site activation (clinicaltrials.gov identifier: NCT04814732).

About Toripalimab

Toripalimab is the first domestic anti-PD-1 monoclonal antibody to obtain marketing approval in China. So far, more than thirty company-sponsored clinical studies covering more than fifteen indications have been conducted globally including in China and the United States. On December 17, 2018, toripalimab was granted conditional approval from the NMPA for the second-line treatment of patients with unresectable or metastatic melanoma. In December 2020, toripalimab was successfully included in the updated National Reimbursement Drug List. In February 2021, toripalimab received NMPA’s conditional approval for the treatment of patients with recurrent or metastatic nasopharyngeal carcinoma ("NPC") after failure of at least two lines of prior systemic therapy. In April 2021, toripalimab received NMPA’s conditional approval for the treatment of patients with locally advanced or metastatic urothelial carcinoma who failed platinum-containing chemotherapy or progressed within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy. In addition, toripalimab has been included in the Guidelines of the Chinese Society of Clinical Oncology (CSCO) for the Diagnosis and Treatment of Melanoma, Head and Neck Tumors, Urothelial Carcinoma and other indications.

In February 2021, the supplemental new drug application (the "sNDA") of toripalimab in combination with cisplatin and gemcitabine as the first-line treatment for patients with locally recurrent or metastatic NPC was accepted for review by the NMPA. In March 2021, toripalimab received Breakthrough Therapy Designation for the first-line treatment of advanced mucosal melanoma by the NMPA. In July 2021, the sNDA for toripalimab in combination with platinum-containing chemotherapy as the first-line treatment for patients with locally advanced or metastatic esophageal squamous cell carcinoma was accepted for review by the NMPA.

In terms of international development, the first toripalimab Biological License Application (BLA) has been submitted to the FDA for the treatment of recurrent or metastatic NPC. The FDA has granted two Breakthrough Therapy designations for toripalimab in combination with chemotherapy for the first line treatment of recurrent or metastatic NPC and also for toripalimab monotherapy in second or third line treatment of recurrent or metastatic NPC. Additionally, FDA has granted Fast Track designation for toripalimab for the treatment of mucosal melanoma and orphan drug designations for NPC, mucosal melanoma and soft tissue sarcoma.

On September 20, 2021 The Case Comprehensive Cancer Center, Northeast Ohio’s coordinated effort to combat cancer, reported that it has earned an additional $12 million from the National Cancer Institute (NCI) as a two-year merit-based extension (Press release, Case Western Reserve University, SEP 20, 2021, View Source [SID1234587958]). The center is the first of two NCI-designated cancer centers to be awarded this prestigious distinction, only available to top-tier centers in the country.

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!

The center’s current Cancer Center Support Grant was last renewed in 2017 when it received an "exceptional" rating—the highest possible—along with $27.9 million to continue lifesaving work from 2018-2023. The Cancer Center’s recent application to extend this funding was approved based on its sustained exceptional progress, stability and longevity.

"This is a fantastic achievement for the Case Comprehensive Cancer Center," said Alan Diehl, deputy director and chief operating officer for the Case Comprehensive Cancer Center and the Leonard and Jean Skeggs Professor and chair of the Department of Biochemistry at the Case Western Reserve School of Medicine. "The merit extension reflects the leadership by Director Stan Gerson and an exceptional team, all of whom focus on providing the best cancer interventions available to our community. It is an honor to be part of such a dynamic partnership."

Photo of Stan Gerson
Stan Gerson
Stan Gerson, interim dean and the Asa and Patricia Shiverick-Jane Shiverick (Tripp) Professor of Hematological Oncology at the Case Western Reserve School of Medicine, has led the center since 2004. He has been continuously recognized for his leadership and for developing such initiatives as implementing a strategic planning effort and enhanced transdisciplinary collaborations, dedicating efforts to address health disparities and community health, and recruiting talented senior leaders and researchers.

"We are humbled to be one of the first centers to receive this new extension and hope a number of other exceptional centers will soon follow," Gerson said. "Our consortium is quite robust and committed to the highest quality of cancer research and impact. This extension will allow us to seamlessly continue driving research focused on the diagnosis, treatment and prevention of cancer, directly impacting the patients and communities we serve."

Among the center’s recent achievements over the past year:

A retreat of program leaders with its Community Advisory Board coordinated by its Office of Community Outreach and Engagement.
Implementation of a strong support program for diversity and equity.
Development of a new "disease ribbons" concept that helps link the breadth of disease-focused research across programs and into translational and clinical applications.
The center is one of just 51 NCI-designated comprehensive cancer centers nationally and one of a small handful to earn the exceptional rating. More than 400 physicians and scientists across the three partner institutions are brought together through six scientific research programs: Cancer Genomics & Epigenomics, Molecular Oncology, Immune Oncology, Developmental Therapeutics, Cancer Imaging, and Population & Cancer Prevention.

The center is known for being a research leader in basic, clinical and population sciences and for providing exemplary service to Northeast Ohio. In addition, the center has built a national reputation for research in colorectal cancers, leukemia and myelodysplastic syndrome (MDS), brain, lung, kidney and prostate cancers.

Combined, Cleveland Clinic and University Hospitals treat nearly 19,000 new cancer patients each year. Because these hospitals are part of an NCI-designated comprehensive cancer center, these patients have more opportunities to participate in a broad range of cutting-edge clinical trials; they also benefit from the concentration of expertise among the three organizations.

"We are grateful for this merit extension, which is a testament to the outstanding research and patient care delivered by Cleveland Clinic Taussig Cancer Institute and Case Comprehensive Cancer Center," said Jame Abraham, deputy director for Cleveland Clinic, Case Comprehensive Cancer Center, acting chair of the Cleveland Clinic Taussig Cancer Institute and a professor at Case Western Reserve School of Medicine. "This support by the National Cancer Institute will allow us to continue focusing on exploring the intricacies of cancer and discovering new treatment options for our patients."

"University Hospitals celebrates the well-deserved merit extension granted by the National Cancer Institute to the Case Comprehensive Cancer Center," said Theodoros N. Teknos, deputy director for University Hospitals for the Case Comprehensive Cancer Center, president and scientific director of University Hospitals Seidman Cancer Center, and a professor of otolaryngology at Case Western Reserve’s School of Medicine. "This recognition serves as validation that Cleveland’s major research institutions are at the forefront of discoveries in cancer prevention, early detection and cure."

The center is also lauded for its training, education and career-development programs for cancer trainees, from high school through junior faculty. In addition, it is home to the NCI-supported Paul Calabresi Clinical Oncology Scholar Training to support clinical investigators across the institutions, one of the longest-running awards of this type in the country. Since its founding in 1987 by Case Western Reserve and University Hospitals, the center has held an NCI designation and attained "comprehensive" status in 1998. Cleveland Clinic formally joined the consortium in 2003.

On September 20, 2021 Seagen Inc. (Nasdaq: SGEN) and Genmab A/S (Nasdaq: GMAB) reported that the U.S. Food and Drug Administration (FDA) has granted accelerated approval to TIVDAK (tisotumab vedotin-tftv), the first and only approved antibody-drug conjugate (ADC) for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy (Press release, Seagen, SEP 20, 2021, View Source [SID1234587993]). TIVDAK is approved under the FDA’s Accelerated Approval Program based on tumor response and the durability of the response. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.1

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!

"Once recurrent or metastatic cervical cancer progresses, there is a need for more options for these patients," said Robert L. Coleman, M.D., Chief Scientific Officer, US Oncology Research and lead investigator of the innovaTV 204 clinical trial. "This is an important development for patients with recurrent or metastatic cervical cancer."

In the innovaTV 204 clinical trial, TIVDAK was evaluated in 101 patients with recurrent or metastatic cervical cancer who had received no more than two prior systemic regimens in the recurrent or metastatic setting, including at least one prior platinum-based chemotherapy regimen. Results from the trial showed a 24 percent confirmed objective response rate (ORR) (95% CI; 15.9-33.3), as assessed by an independent review committee (IRC) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. The median duration of response (DOR) was 8.3 months (95% CI; 4.2 to not reached).

The prescribing information for TIVDAK includes a BOXED WARNING for ocular toxicity, and Warnings for peripheral neuropathy, hemorrhage, pneumonitis, and embryo-fetal toxicity. The most common (≥25%) adverse reactions, including laboratory abnormalities, were hemoglobin decreased (52%), fatigue (50%), lymphocytes decreased (42%), nausea (41%), peripheral neuropathy (39%), alopecia (39%), epistaxis (39%), conjunctival adverse reactions (37%), hemorrhage (32%), leukocytes decreased (30%), creatinine increased (29%), dry eye (29%), prothrombin international normalized ratio increased (26%), activated partial thromboplastin time prolonged (26%), diarrhea (25%), and rash (25%). Please see Important Safety Information below.1

"We are thrilled to see this new treatment approved by the FDA. We are grateful to have another option for this devastating disease," said Tamika Felder, Founder, Cervivor.

"We are pleased with the accelerated approval of TIVDAK, Seagen’s third FDA-approved antibody-drug conjugate, and fourth approved medicine. Our mission at Seagen is to develop medicines that make a difference for people impacted by cancer," said Roger Dansey, M.D., Chief Medical Officer, Seagen.

"TIVDAK’s approval as a monotherapy in the U.S. is an important milestone for women with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, as they are in need of a new treatment option and we look forward to making it available to them," said Jan van de Winkel, Ph.D., Chief Executive Officer, Genmab. "The journey towards the approval of TIVDAK started nearly two decades ago with innovative research by scientists at Genmab and Seagen and reflects on our purpose of making an impact in the lives of cancer patients and their families. Today’s announcement marks Genmab’s evolution into a fully integrated biotechnology company and we would like to thank patients, caregivers, investigators and our collaborators for their participation in our clinical studies."

The Biologics License Application (BLA) for TIVDAK was submitted in February 2021 and accepted with Priority Review in April 2021. The submission was based on the results of the innovaTV 204 trial.

The FDA’s Accelerated Approval Program allows for approval of a medicine based on a surrogate endpoint that is reasonably likely to predict clinical benefit, if the medicine fills an unmet medical need for a serious condition. A global, randomized phase 3 clinical trial (innovaTV 301) is underway and is also intended to support global registrations.

About Cervical Cancer

It is estimated that in 2021, more than 14,480 new cases of invasive cervical cancer will be diagnosed in the U.S., and 4,290 women will die from the disease.2 Cervical cancer remains one of the leading causes of cancer death in women globally, with over 311,000 women dying of the disease in 2018.3

About the innovaTV 204 Trial

The innovaTV 204 trial (NCT03438396/GOG-3023/ENGOT-cx6) is an open-label, multicenter, single-arm phase 2 trial that evaluated tisotumab vedotin in 101 patients with recurrent or metastatic cervical cancer who had received no more than two prior systemic regimens in the recurrent or metastatic setting, including at least one prior platinum-based chemotherapy regimen. Patients were excluded if they had active ocular surface disease, any prior episode of cicatricial conjunctivitis or Stevens-Johnson syndrome, Grade ≥2 peripheral neuropathy or known coagulation defects leading to an increased risk of bleeding. The main efficacy outcome measures were confirmed ORR per RECIST v1.1 as assessed by an IRC and DOR.1

The study was conducted by Genmab in collaboration with Seagen, European Network of Gynaecological Oncological Trial Groups (ENGOT) and the GOG Foundation, Inc. (GOG). For more information about the phase 2 innovaTV 204 clinical trial and other clinical trials with tisotumab vedotin, please visit www.clinicaltrials.gov.

About TIVDAK (tisotumab vedotin-tftv)

TIVDAK (tisotumab vedotin-tftv) is an ADC composed of Genmab’s human monoclonal antibody directed to tissue factor (TF) and Seagen’s ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody. Nonclinical data suggests that the anticancer activity of TIVDAK is due to the binding of the ADC to TF expressing cancer cells, followed by internalization of the ADC-TF complex, and release of MMAE via proteolytic cleavage. MMAE disrupts the microtubule network of actively dividing cells, leading to cell cycle arrest and apoptotic cell death. In vitro, TIVDAK also mediates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity.1

TIVDAK (tisotumab vedotin-tftv) for injection, for intravenous use, 40 mg Important Safety Information

BOXED WARNING: OCULAR TOXICITY

TIVDAK caused changes in the corneal epithelium and conjunctiva resulting in changes in vision, including severe vision loss, and corneal ulceration. Conduct an ophthalmic exam at baseline, prior to each dose, and as clinically indicated. Adhere to premedication and required eye care before, during and after infusion. Withhold TIVDAK until improvement and resume, reduce the dose, or permanently discontinue, based on severity.

Warnings and Precautions

Ocular Adverse Reactions occurred in 60% of patients with cervical cancer treated with TIVDAK. The most common were conjunctival adverse reactions (40%), dry eye (29%), corneal adverse reactions (21%), and blepharitis (8%). Grade 3 ocular adverse reactions occurred in 3.8% of patients, including severe ulcerative keratitis in 3.2% of patients. One patient experienced ulcerative keratitis with perforation requiring corneal transplantation. Cases of symblepharon were reported in patients with other tumor types treated with TIVDAK at the recommended dose.

In innovaTV 204, 4% of patients experienced visual acuity changes to 20/50 or worse, including 1% of patients who experienced a visual acuity change to 20/200. Of the patients who experienced decreased visual acuity to 20/50 or worse, 75% resolved, including the patient who experienced decreased visual acuity to 20/200.

Refer patients to an eye care provider for an ophthalmic exam including visual acuity and slit lamp exam at baseline, prior to each dose, and as clinically indicated. Adhere to premedication and required eye care to reduce the risk of ocular adverse reactions. Promptly refer patients to an eye care provider for any new or worsening ocular signs and symptoms. Withhold dose, reduce the dose, or permanently discontinue TIVDAK based on the severity of the adverse reaction.

Peripheral neuropathy (PN) occurred in 42% of cervical cancer patients treated with TIVDAK across clinical trials; 8% of patients experienced Grade 3 PN. PN adverse reactions included peripheral neuropathy (20%), peripheral sensory neuropathy (11%), peripheral sensorimotor neuropathy (5%), motor neuropathy (3%), muscular weakness (3%), and demyelinating peripheral polyneuropathy (1%). One patient with another tumor type treated with TIVDAK at the recommended dose developed Guillain- Barré syndrome.

Monitor patients for signs and symptoms of neuropathy. For new or worsening PN, withhold, dose reduce, or permanently discontinue TIVDAK based on the severity of PN.

Hemorrhage occurred in 62% of cervical cancer patients treated with TIVDAK across clinical trials. The most common all grade hemorrhage adverse reactions were epistaxis (44%), hematuria (10%), and vaginal hemorrhage (10%). Grade 3 hemorrhage occurred in 5% of patients.

Monitor patients for signs and symptoms of hemorrhage. For patients experiencing pulmonary or CNS hemorrhage, permanently discontinue TIVDAK. For Grade ≥2 hemorrhage in any other location, withhold until bleeding has resolved, blood hemoglobin is stable, there is no bleeding diathesis that could increase the risk of continuing therapy, and there is no anatomical or pathologic condition that can increase the risk of hemorrhage recurrence. After resolution, either resume treatment or permanently discontinue TIVDAK.

Pneumonitis: Severe, life-threatening, or fatal pneumonitis can occur in patients treated with antibody-drug conjugates containing vedotin, including TIVDAK. Among patients with cervical cancer treated with TIVDAK across clinical trials, 2 patients (1.3%) experienced pneumonitis, including 1 patient who had a fatal outcome.

Monitor patients for pulmonary symptoms indicative of pneumonitis. Infectious, neoplastic, and other causes for symptoms should be excluded through appropriate investigations.

Withhold TIVDAK for patients who develop persistent or recurrent Grade 2 pneumonitis and consider dose reduction. Permanently discontinue TIVDAK in all patients with Grade 3 or 4 pneumonitis.

Embryo-fetal toxicity: TIVDAK can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TIVDAK and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TIVDAK and for 4 months after the last dose.

Adverse Reactions

Serious adverse reactions occurred in 43% of patients; the most common (≥3%) were ileus (6%), hemorrhage (5%), pneumonia (4%), PN, sepsis, constipation, and pyrexia (each 3%). Fatal adverse reactions occurred in 4% of patients who received TIVDAK, including septic shock, pneumonitis, sudden death, and multisystem organ failure (each 1%).

Adverse reactions leading to permanent discontinuation occurred in 13% of patients receiving TIVDAK; the most common (≥3%) were PN (5%) and corneal adverse reactions (4%). Adverse reactions leading to dose interruption occurred in 47% of patients; the most common (≥3%) were PN (8%), conjunctival adverse reactions (4%), and hemorrhage (4%). Adverse reactions leading to dose reduction occurred in 23% of patients; the most common (≥3%) were conjunctival adverse reactions (9%) and corneal adverse reactions (8%).

The most common (≥25%) adverse reactions, including laboratory abnormalities, were hemoglobin decreased (52%), fatigue (50%), lymphocytes decreased (42%), nausea (41%), PN (39%), alopecia (39%), epistaxis (39%), conjunctival adverse reactions (37%), hemorrhage (32%), leukocytes decreased (30%), creatinine increased (29%), dry eye (29%), prothrombin international normalized ratio increased (26%), activated partial thromboplastin time prolonged (26%), diarrhea (25%), and rash (25%).

Drug interactions

Strong CYP3A4 Inhibitors: Concomitant use with strong CYP3A4 inhibitors may increase unconjugated monomethyl auristatin E (MMAE) exposure, which may increase the risk of TIVDAK adverse reactions. Closely monitor patients for TIVDAK adverse reactions.

Use in Specific Populations

Moderate or Severe Hepatic Impairment: MMAE exposure and adverse reactions are increased. Avoid use.

Lactation: Advise lactating women not to breastfeed during TIVDAK treatment and for at least 3 weeks after the last dose.