Cancer remains one of the leading causes of death globally, with an estimated 10 million cancer deaths in 2020 alone. Major European pharmaceutical companies are continuously conducting clinical trials to develop innovative new cancer treatments and improve patient outcomes. This article summarizes recent advances from Phase 1-3 clinical trials conducted by 7 major European pharma companies across various cancer types and therapeutic areas.
AstraZeneca has an extensive pipeline of investigational cancer medicines, several of which have recently demonstrated positive results in clinical trials.
Enhertu (trastuzumab deruxtecan), a HER2-directed antibody drug conjugate, showed clinically meaningful and durable responses in patients with HER2-expressing breast, gastric, lung and colorectal cancers in the phase 2 DESTINY-PanTumor02 trial (Advanced Solid Tumors). Another phase 2 trial, DESTINY-Lung02, found Enhertu induced strong and durable tumor responses in patients with previously treated HER2-mutant lung cancer (NSCLC).
Imfinzi (durvalumab) plus chemotherapy significantly improved pathologic complete response rates compared to chemotherapy alone for gastric and gastroesophageal junction cancers in the phase 3 MATTERHORN trial (Gastric Cancer). The combination also reduced the risk of disease recurrence, progression or death by 32% versus placebo in the phase 3 AEGEAN trial for resectable non-small cell lung cancer (NSCLC) (NSCLC).
Tagrisso (osimertinib) plus chemotherapy showed strong improvement in progression-free survival versus chemotherapy alone for EGFR-mutated advanced NSCLC in the phase 3 FLAURA2 trial (NSCLC). In the phase 3 ADAURA trial, adjuvant Tagrisso demonstrated impressive 5-year overall survival of 88% in early-stage EGFR-mutated NSCLC (NSCLC).
Bayer has active research programs focused on targeted therapies, immunotherapies and radiation therapies across cancers like prostate, liver and bladder.
Darolutamide, an oral androgen receptor inhibitor, in combination with androgen deprivation therapy and docetaxel showed significant survival benefit over androgen deprivation therapy and docetaxel alone for metastatic hormone-sensitive prostate cancer in the phase 3 ARASENS trial (Prostate Cancer). The phase 3 ARAMIS trial found darolutamide plus androgen deprivation therapy successfully delayed metastasis in men with non-metastatic castration-resistant prostate cancer (Prostate Cancer).
The vitamin A derivative alitretinoin showed potential as a chemotherapy-free treatment option for patients with relapsed/refractory peripheral T-cell lymphoma in a phase 2 trial (Peripheral T-Cell Lymphoma).
Radium-223 dichloride, an alpha emitter, demonstrated favorable overall survival and safety in real-world data from the phase 4 REASSURE trial as a treatment for metastatic castration-resistant prostate cancer (Prostate Cancer).
GlaxoSmithKline has a broad oncology pipeline spanning multiple modalities such as cell therapies, antibody drug conjugates and targeted small molecules.
The anti-CD19 antibody drug conjugate belantamab mafodotin induced deep and durable responses as a monotherapy for relapsed/refractory multiple myeloma in the phase 3 DREAMM-2 study (Multiple Myeloma). Further, the BCMA-targeting CAR-T therapy gsk3368715 showed promising efficacy and safety alone or combined with pembrolizumab for relapsed/refractory multiple myeloma (Multiple Myeloma).
Dostarlimab, an anti-PD-1 antibody, led to significant improvement in progression-free survival over chemotherapy for recurrent/advanced endometrial cancer in the phase 3 GARNET trial (Endometrial Cancer). The phase 3 RUBY trial also found dostarlimab plus chemotherapy extended progression-free survival and overall survival versus chemotherapy alone for this patient population (Endometrial Cancer).
The PARP inhibitor niraparib improved progression-free survival to 3.5 years with an acceptable long-term safety profile as maintenance therapy for newly diagnosed ovarian cancer after platinum-based chemotherapy in the phase 3 PRIMA/ENGOT-OV26/GOG-3012 trial (Ovarian Cancer).
Janssen produces leading therapies for blood cancers and prostate cancer. Several of its developmental assets have exhibited promise in recent clinical evaluation.
Teclistamab, a bispecific T-cell engager targeting BCMA, achieved deep and durable responses with an overall response rate of 61% in heavily pretreated multiple myeloma in the phase 1 MajesTEC-1 study (Multiple Myeloma). In the phase 1 CARTITUDE-1 study, the BCMA-targeting CAR-T therapy ciltacabtagene autoleucel induced high response rates and durable remissions in multiple myeloma (Multiple Myeloma).
Apalutamide, a next-generation oral androgen receptor inhibitor, demonstrated clinically meaningful improvement in overall survival for patients with metastatic hormone-sensitive prostate cancer in the phase 3 TITAN study when added to androgen deprivation therapy (Prostate Cancer). Another phase 3 trial, SPARKLE, found apalutamide safely extended event-free survival in pediatric and young adult patients with high-risk, metastatic soft tissue sarcoma (Soft Tissue Sarcoma).
Merck is developing immunotherapies targeting PD-1/PD-L1 as well as novel combinations for hard-to-treat cancers.
The phase 3 JAVELIN Bladder 100 study showed maintenance therapy with the PD-L1 inhibitor avelumab led to significant survival benefit in advanced urothelial carcinoma progressing after platinum-based chemotherapy (Bladder Cancer). Based on this trial, avelumab became the first immunotherapy approved by the FDA for first-line maintenance in advanced bladder cancer.
Adding the investigational bifunctional immunotherapy bintrafusp alfa targeting TGF-β and PD-L1 to chemotherapy resulted in superior progression-free survival and overall survival compared to chemotherapy plus placebo as initial treatment for metastatic biliary tract cancer in the phase 2 TROPiCS-02 study (Biliary Tract Cancer).
Combining the bispecific PD-L1 and TGFβ trap bintrafusp alfa with chemotherapy also significantly improved objective response rate versus chemotherapy alone for metastatic non-squamous NSCLC in the phase 3 CENTAURUS trial (NSCLC).
While best known for diabetes care, Novo Nordisk has expanded into oncology with a robust hematological malignancies pipeline.
The oral SMAC mimetic birinapant demonstrated clinical activity and acceptable tolerability in combination with several chemotherapy regimens across relapsed/refractory blood cancers like acute myeloid leukemia in a phase 1 trial (Blood Cancers).
Another phase 1 study found the IDO1 enzyme inhibitor epacadostat combined with the PD-1 inhibitor pembrolizumab showed antitumor activity across multiple solid tumor types, warranting further clinical investigation (Solid Tumors).
The oral CEP-701, a tropomyosin receptor kinase (Trk) inhibitor, exhibited a favorable safety profile and encouraging efficacy signals in heavily pretreated neuroblastomas expressing Trk in a phase 1 pediatric trial (Neuroblastoma).
Roche leads in breast cancer care with multiple approved targeted therapies and promising candidates in the pipeline.
In the phase 3 HARMONIA trial, combining Kadcyla (T-DM1), Herceptin and Perjeta led to the longest progression-free survival reported to date (nearly 28 months) for patients with high-risk HER2-positive early breast cancer (Breast Cancer).
The oral SERD giredestrant elicited clinical benefit over aromatase inhibitor therapy in ER-positive, HER2-negative metastatic breast cancer in the phase 3 AMEERA-5 trial (Breast Cancer). Based on these results, Roche plans to submit giredestrant for regulatory approval.
Polatuzumab vedotin, an anti-CD79b antibody drug conjugate, plus MabThera/Rituxan demonstrated clinically meaningful improvement in progression-free survival and overall survival compared to MabThera/Rituxan alone for relapsed/refractory diffuse large B-cell lymphoma in the phase 3 POLARIX trial (B-cell lymphoma).
Sanofi is strengthening its presence in oncology with strategic collaborations and acquisitions focusing on antibody therapies.
The PD-1 inhibitor Libtayo (cemiplimab) combined with chemotherapy extended overall survival versus chemotherapy alone for first-line advanced non-small cell lung cancer in the phase 3 EMPOWER-Lung 3 trial (NSCLC). Based on these positive results, Libtayo was approved by the FDA in this setting.
Isatuximab plus standard of care triplet regimens induced high response rates and improved progression-free survival in patients with newly diagnosed multiple myeloma in the phase 3 GMMG-CONCEPT and IMROZ trials (Multiple Myeloma). The IKEMA phase 3 study also showed addition of isatuximab to carfilzomib and dexamethasone led to deeper responses and prolonged progression-free survival in relapsed multiple myeloma (Multiple Myeloma).
Conclusion
These recent clinical trial findings demonstrate the ongoing commitment of leading European pharma companies to develop transformative new therapeutic options for cancer patients worldwide. Collaborations between industry and academia will be critical to build on this progress and continue advancing the standard of care across various malignancies.
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