Reading our newsletter will keep you up to date with last month’s news items on oncology drug development!

NEWS AND PUBLICATIONS

MyPathway: a multi-center, open-label, phase 2a, multiple basket study

MyPathway evaluates the activity of FDA-approved therapies in non-indicated tumors with potentially actionable molecular alterations. In this study, the data presents an analysis of patients with metastatic biliary tract cancers with HER2 amplification, overexpression, or both treated with a dual anti-HER2 regimen, pertuzumab plus trastuzumab.

MyPathway is a non-randomized, multicentre, open-label, phase 2a, multiple basket study. Patients aged 18 years and older with previously treated metastatic biliary tract cancers with HER2 amplification, HER2 overexpression, or both and an Eastern Cooperative Oncology Group performance status of 0–2 were enrolled. The primary endpoint was investigator-assessed objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The primary outcome and adverse events were analyzed in all patients who received at least one dose of pertuzumab and trastuzumab. This trial is registered with ClinicalTrials.govNCT02091141, and is ongoing.

In summary so far, 39 patients enrolled and were evaluable for anti-tumour activity by the March 10, 2020, data cutoff date. Nine of 39 patients achieved a partial response (objective response rate 23% [95% CI 11–39]). Grade 3–4 treatment-emergent adverse events were reported in 18 (46%) of 39 patients, most commonly increased alanine aminotransferase and increased aspartate aminotransferase (each five [13%] of 39). Treatment-related grade 3 adverse events were reported in three (8%) of 39 patients, including increased alanine aminotransferase, aspartate aminotransferase, blood alkaline phosphatase, and blood bilirubin. Serious treatment-emergent adverse events were observed in ten (26%) of 39 patients, of which only abdominal pain occurred in more than one patient (two [5%] of 39). There were no treatment-related serious adverse events, treatment-related grade 4 events, or deaths. Based on the current data, treatment was well tolerated in patients with previously treated HER2-positive metastatic biliary tract cancer. The response rate is promising for the initiation of randomized, controlled trials of pertuzumab plus trastuzumab in this patient population.

Neoadjuvant cabozantinib and nivolumab convert locally advanced hepatocellular carcinoma into resectable disease with enhanced anti-tumor immunity

A potentially curative hepatic resection is the optimal treatment for hepatocellular carcinoma (HCC) but most patients are not candidates for resection and most resected HCCs eventually recur. Neoadjuvant systemic therapy for HCC has been limited due to a lack of effective systemic agents. Here, in a single-arm phase 1b study, the feasibility of neoadjuvant cabozantinib and nivolumab in patients with HCC, including patients outside of traditional resection criteria was evaluated (NCT03299946). Of 15 patients enrolled, 12 (80%) underwent successful margin-negative resection and 5 out of 12 (42%) had major pathological responses. In-depth biospecimen profiling demonstrated an enrichment in effector T cells, as well as tertiary lymphoid structures, CD138+ plasma cells, and a distinct spatial arrangement of B-cells in responders compared to non-responders, indicating an orchestrated B cell contribution to anti-tumor immunity in HCC.

INDUSTRY

Amgen is set to acquire Tenebio, an antibody drug developer

Amgen is committing up to $1.6 billion in milestones to acquire Teneobio, an antibody drug developer with expertise in developing bi-specifics and multi-specifics. Amgen cited Teneobio’s “T-cell engager platform, which expands on Amgen’s existing position in bi-specific T-cell engagers by providing a differentiated, but complementary, approach to Amgen’s current BiTE platform.” The acquisition gives Amgen a phase 1 program for a drug dubbed TNB-585, a PSMA/CD3 bispecific T-cell engager in development for castration-resistant prostate cancer. Amgen plans to line that one up alongside acapatamab (formerly AMG 160) and AMG 509 as a complementary therapy.

Artios Pharma announced the completion of a US$153 million (£110 million) Series C financing to fund further development of its promising clinical-stage pipeline

Artios Pharma Limited (Artios), a leading DNA Damage Response (DDR) company exploiting a broad DDR-based platform and small molecule drug discovery, announced the completion of a US$153 million (£110 million) Series C financing to fund further development of its promising clinical-stage pipeline. The funding supports Artios to advance beyond synthetic lethality and to continue the exploitation of the full spectrum of oncology vulnerabilities presented by the DNA Damage Response through deployment of Artios’ DDR-based platform and small molecule drug discovery capabilities. The financing supports an expansion of potentially best-in-class ATR inhibitor and first-in-class highly selective Polθ inhibitor programs by enabling clinical development in multiple tumor settings and biological backgrounds of single agent and combination therapies.

In a recently started trial, a small-molecule ATR (Ataxia telangiectasia and Rad3-related kinase) inhibitor, ART0380, is being investigated in patients with advanced or metastatic solid tumors. The trial is an open-label, multi-center, phase 1/2a study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ART0380 as a monotherapy and in combination with gemcitabine in patients with advanced or metastatic solid cancers. The study will enroll up to 180 patients and will be conducted at multiple oncology centers across the USA, UK, and Europe. Full details can be found at www.clinicaltrials.gov under the identifier NCT04657068.

EMA

In the July 2021 meeting, the Committee for Medical Products for Human Use (CHMP) adopted a positive opinion for:

New Hybrid Medicines:

  • Imatinib Koanaa (imatinib; KOANAA Healthcare GmbH) is intended for the treatment of leukaemia and gastrointestinal stromal tumors.The active substance of Imatinib Koanaa is imatinib, a protein kinase inhibitor that potently inhibits the activity of the Bcr-Abl tyrosine kinase (TK), as well as several receptor TKs. Imatinib Koanaa is a hybrid medicine of Glivec, which has been authorised in the EU since 7 November 2001 in the form of film-coated tablets. Imatinib Koanaa contains the same active substance as Glivec, but it is an oral solution.

Withdrawal of post-authorization marekting application:

  • Tecentriq (atezolizumab, Roche Registration GmbH), intended to treat early or locally advanced triple-negative breast cancer, is a monoclonal antibody, a to PD-L1 (programmed death-ligand 1), which is present on many cancer cells. PD-L1 acts to switch off immune cells that would otherwise attack the cancer cells. By reducing its effects, Tecentriq increases the ability of the immune system to attack the cancer cells and thereby slow down progression of the disease. The company presented data from the Impassion031 study of 333 patients who received either Tecentriq or placebo in combination with nab-paclitaxel and anthracycline-based chemotherapy, before going on to have surgery. The main measure of effectiveness was how many patients no longer had tumors in their breasts or lymph nodes after surgery. Patients were followed-up afterwards to assess longer-term benefits and to see if their cancer came back. The study data provided do not allow the committee to conclude on a positive benefit : risk balance.

Updated Recommendations on eligibility for PRIME (up to June2021) for oncology products show 27 applications accepted and 82 applications denied.

FDA

In July, the FDA granted approval for:

  • Asparaginase erwinia chrysanthemi (recombinant)-rywn) (Rylaze, Jazz Pharmaceuticals, Inc.) as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adult and pediatric patients 1 month or older who have developed hypersensitivity to E. coli-derived asparaginase.
  • Enfortumab vedotin-ejfv (Padcev, Astellas Pharma US, Inc.), a Nectin-4-directed antibody and microtubule inhibitor conjugate, for adult patients with locally advanced or metastatic urothelial cancer who:
    • have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand (PD-L1) inhibitor and platinum-containing chemotherapy, or
    • are ineligible for cisplatin-containing chemotherapy and have previously received one or more prior lines of therapy.
  • Daratumumab and hyaluronidase-fihj (Darzalex Faspro, Janssen Biotech, Inc.) in combination with pomalidomide and dexamethasone for adult patients with multiple myeloma who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor.
  • Pembrolizumab (Keytruda, Merck) in combination with lenvatinib (Lenvima, Eisai) for patients with advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
  • Pembrolizumab (Keytruda, Merck) for high-risk, early-stage, triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery. 

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