Investigational Acasunlimab (DuoBody® -PD-L1x4-1BB) in Combination with Pembrolizumab Demonstrates Meaningful Clinical Activity in Phase 2 Trial in Patients with Previously Treated Metastatic Non-small Cell Lung Cancer (mNSCLC)

• Initial data from the ongoing Phase 2 trial showed a 12-month overall survival rate of 69% and a median overall survival of 17.5 months in patients with previously treated PD-L1-positive metastatic non-small cell lung cancer treated with a combination of acasunlimab and pembrolizumab every six weeks
• Data from this ongoing Phase 2 study to inform the planned pivotal Phase 3 trial, which is expected to start before the end of 2024

COPENHAGEN, Denmark, and MAINZ, Germany, June 1, 2024 — Genmab A/S (Nasdaq: GMAB, “Genmab”) and BioNTech SE (Nasdaq: BNTX, “BioNTech”) today announced initial data from the ongoing Phase 2 trial (NCT05117242) evaluating acasunlimab (DuoBody-PD-L1x4-1BB), an investigational bispecific antibody also known as GEN1046/BNT311, as monotherapy and in combination with pembrolizumab in patients with PD-L(1)-positive metastatic non-small cell lung cancer (“mNSCLC”) who had disease progression following one or more prior lines of anti-PD(L)1-containing treatment. The results showed a 12-month overall survival (“OS”) rate of 69%, a median overall survival (“mOS”) of 17.5 months, and a 30% overall response rate (“ORR”) (confirmed ORR 17%) at the time of data cut-off in patients treated with the combination of acasunlimab and pembrolizumab every six weeks. The findings were presented at the 2024 American Society of Clinical Oncology (“ASCO”) Annual Meeting held in Chicago, IL from May 31-June 4, 2024.

The Phase 2 study randomized a total of 113 patients in three arms, evaluating acasunlimab alone (Arm A) and in combination with pembrolizumab (Arms B and C). The objective response analysis was conducted for 62 centrally confirmed PD-L1-positive efficacy-evaluable patients. The OS was evaluated in all centrally confirmed PD-L1-positive patients (n=80). Arm A showed a mOS rate of 5.5 months, a 50% disease control rate (DCR) and a 31% ORR (confirmed ORR 13%) in patients treated with acasunlimab alone. An 8.6 months mOS, a 59% DCR and a 21% ORR (confirmed ORR 18%) for treatment of acasunlimab in combination with pembrolizumab every three weeks (Arm B) and a 17.5 months mOS, a 75% DCR and a 30% ORR (confirmed ORR 17%) when the combination was administered every six weeks (Arm C). Anti-tumor activity was observed in patients with a tumor proportion score (“TPS”) of 1–49% and ≥50%, in patients with <6 months and ≥6 months of previous immune checkpoint inhibitor (“CPI”) treatment, and in patients with squamous and non-squamous histology.

Adverse events were consistent with the safety profiles of the individual drugs and treatment related adverse events (“TRAEs”) were primarily grade 1 and 2. The most common TRAEs (all grades) in Arm A were asthenia (22.7%), diarrhea (18.2%), nausea (18.2%), anemia (13.6%), and liver-related events (13.6%). In the combination arms (Arms B and C), the most common TRAEs were liver-related events (28.6%, 18.4%), fatigue (21.4%, 8.2%), asthenia (12%, 12.2%), and diarrhea (12%, 10.2%). Overall, a lower incidence of grade ≥3 TRAEs, treatment-related liver-related events and lower discontinuation rates were observed with the combination regimen therapy administered every six weeks. Transaminase elevations were generally asymptomatic and manageable with the administration of steroids and/or treatment delay and resolved more rapidly in patients treated with the combination therapy administered every six weeks.

“We are encouraged by the findings of this ongoing Phase 2 study. The initial results of acasunlimab in combination with pembrolizumab administered every 6 weeks suggest a potential meaningful impact on patients with metastatic non-small cell lung cancer,” said Judith Klimovsky, Executive Vice President & Chief Development Officer at Genmab. “We will continue to evaluate these data to inform further development of acasunlimab including a planned Phase 3 trial as we remain committed to investigate acasunlimab as a potential treatment option.”

“Most patients with mNSCLC have limited treatment options following progression on first-line checkpoint inhibitor therapy. For these patients, chemotherapy remains the main treatment despite limited efficacy and considerable toxicity,” said Prof. Özlem Türeci, M.D., Chief Medical Officer and Co-Founder at BioNTech. “The data of our Phase 2 trial show that the combination of acasunlimab with PDL1-blockade may be a suitable approach in this heavily pretreated patient population.”

About the GCT1046-04 Clinical Trial

The GCT1046-04 trial (NCT05117242) is a randomized, open-label trial evaluating the safety and efficacy of acasunlimab in patients with relapsed/refractory metastatic non-small cell lung cancer (“mNSCLC”) after treatment with standard of care therapy containing immune checkpoint inhibitor therapy. Patients with stage IV NSCLC with at least one prior line of systemic therapy containing an anti-PD-1/PD-L1 and a tumor PD-L1 expression in ≥1% of the tumor cells are included in the study. The primary endpoint of the trial is the overall response rate (“ORR”). Key secondary endpoints include overall survival (“OS”), progression free survival (“PFS”), time to response (“TTR”), duration of response (“DOR”), and safety. More information on this trial can be found at clinicaltrials.gov.

About Non-small Cell Lung Cancer (NSCLC)

Non-small cell lung cancer (“NSCLC”) is the most common type of lung cancer, accounting for about 85% of all reported cases. NSCLC starts in cells that line the airways and can grow into nearby tissues or spread to other parts of the body. NSCLC is often diagnosed at an advanced stage, when it is hard to treat and has a poor prognosis. The survival rate of patients with NSCLC varies depending on the stage at diagnosis.^i,ii,iii,The treatment of NSCLC depends on the stage, subtype, and biomarker status of the disease, and may include surgery, radiation therapy, chemotherapy, targeted therapy, immunotherapy, or a combination of these modalities.

About Acasunlimab (GEN1046/BNT311)
Acasunlimab (GEN1046/BNT311) is an investigational PD-L1x4-1BB bispecific antibody fusing Genmab's proprietary DuoBody^® technology platform and BioNTech’s proprietary immunomodulatory antibodies. Acasunlimab is designed to elicit an antitumor response via conditional activation of 4-1BB on T cells and natural killer cells, which is strictly dependent on simultaneous binding of the PD-L1 arm. Acasunlimab is being developed in collaboration by BioNTech and Genmab under a license and collaboration agreement. The candidate is currently being investigated in three clinical trials: (1) a Phase 1/2 safety trial in patients with multiple solid tumors, (2) a Phase 1 dose escalation trial in patients with advanced solid tumors in Japan, and (3) a randomized Phase 2 safety and efficacy trial with acasunlimab as a monotherapy and in combination with pembrolizumab in patients with NSCLC who have failed previous standard of care treatments with immune checkpoint inhibitors. Please visit www.clinicaltrials.gov for more information.

About Genmab
Genmab is an international biotechnology company with a core purpose of guiding its unstoppable team to strive toward improving the lives of patients with innovative and differentiated antibody therapeutics. For 25 years, its passionate, innovative and collaborative team has invented next-generation antibody technology platforms and leveraged translational, quantitative and data sciences, resulting in a proprietary pipeline including bispecific T-cell engagers, antibody-drug conjugates, next-generation immune checkpoint modulators and effector function-enhanced antibodies. By 2030, Genmab’s vision is to transform the lives of people with cancer and other serious diseases with knock-your-socks-off (KYSO^®) antibody medicines.  
  
Established in 1999, Genmab is headquartered in Copenhagen, Denmark, with international presence across North America, Europe and Asia Pacific. For more information, please visit Genmab.com and follow us on LinkedIn and X. 

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About BioNTech

Biopharmaceutical New Technologies (BioNTech) is a global next generation immunotherapy company pioneering novel therapies for cancer and other serious diseases. BioNTech exploits a wide array of computational discovery and therapeutic drug platforms for the rapid development of novel biopharmaceuticals. Its broad portfolio of oncology product candidates includes individualized and off-the-shelf mRNA-based therapies, innovative chimeric antigen receptor (CAR) T cells, several protein-based therapeutics, including bispecific immune checkpoint modulators, targeted cancer antibodies and antibody-drug conjugate (ADC) therapeutics, as well as small molecules. Based on its deep expertise in mRNA vaccine development and in-house manufacturing capabilities, BioNTech and its collaborators are developing multiple mRNA vaccine candidates for a range of infectious diseases alongside its diverse oncology pipeline. BioNTech has established a broad set of relationships with multiple global and specialized pharmaceutical collaborators, including Biotheus, DualityBio, Fosun Pharma, Genentech, a member of the Roche Group, Genevant, Genmab, MediLink, OncoC4, Pfizer and Regeneron.

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ⁱ American Cancer Society. What is Non-Small Cell Lung Cancer? https://www.cancer.org/cancer/types/lung-cancer.html. Accessed May 14, 2024.

ⁱⁱ Mayo Clinic. Non-Small Cell Lung Cancer. https://www.mayoclinic.org/diseases-conditions/lung-cancer/symptoms-causes/syc-20374620. Accessed May 14, 2024.

ⁱⁱⁱ CancerNet. Lung Cancer – Non-Small Cell: Introduction. https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/introduction. Accessed May 14, 2024.