[Corrected 6/17/20, 1:48 pm PT. See below.] GlaxoSmithKline’s years-long oncology resurgence is on track to have two new drugs approved in the US in mid-2020, after the company won a key first-line ovarian cancer indication for Zejula (niraparib) in April. The belantamab mafodotin and dostarlimab approvals also anticipated this year will give GSK its first commercial footholds in the immuno-oncology market – one of four cancer drug categories where the company is developing new therapies.
“We have been a little bit in the shadows and are just getting into the spotlight with some of the more recent work that we’ve made public,” GSK (NYSE: [[ticker:GSK]]) senior vice president and oncology research and development head Axel Hoos told Scrip.
The company reported data for several clinical-stage cancer drug candidates during the American Society of Clinical Oncology (ASCO) meeting held online 29-31 May, including updated results for belantamab mafodotin that showed durable responses and relatively lengthy overall survival for heavily pretreated multiple myeloma patients.
Approval of the B-cell maturation antigen (BCMA)-targeting antibody-drug conjugate (ADC) belantamab mafodotin in fourth-line or later treatment of multiple myeloma would give GSK a first-in-class therapy. (Also see “GSK Files Its BCMA Drug In Multiple Myeloma”—Scrip, 17 Dec, 2019.) It also would be the company’s first approval for a novel oncology drug since GSK completed the sale of its targeted cancer drugs to Novartis AG for $16bn in 2015. (Also see “It’s a wrap: GSK and Novartis megadeal completes”—Scrip, 3 Mar, 2015.)
“Our objective is to be one of the lead players in oncology by offering truly transformational benefit for patients,” Hoos said. “We have shifted our portfolio from oncology 1.0 before the Novartis transaction and it’s now called oncology 2.0 after the Novartis transaction where we basically shifted from largely me-too products or follow-on products to now leading-edge innovation that is able to compete with any other oncology company in the industry.”
While dostarlimab will be the seventh PD-1/L1 inhibitor approved in the US, it will be the second approved for endometrial cancer and it will expand PD-1 inhibition for this disease beyond the front-line treatment of microsatellite stability-high (MSI-high) tumors, where market leader Merck & Co. Inc.’s Keytruda (pembrolizumab) is approved.
Dostarlimab was acquired along with Zejula in the $5bn purchase of Tesaro Inc. (Also see “GSK Embraces PARP Promise With Tesaro Buy”—Scrip, 3 Dec, 2018.) GSK is seeking approval for the drug to treat MSI-high and microsatellite-stable (MSS) recurrent endometrial cancer based on the pivotal Phase 1/2 GARNET clinical trial. (Also see “Tesaro’s On The Right Path With Anti-PD-1 Dostarlimab In Endometrial Cancer”—Scrip, 22 Mar, 2019.)
Similar to dostarlimab, Zejula was not the first PARP inhibitor approved in the first-line ovarian cancer maintenance setting, but it is the first one indicated to treat tumors regardless of BRCA mutation status. The top-selling PARP inhibitor – AstraZeneca PLC/Merck’s Lynparza (olaparib)—is approved as a first-line maintenance therapy, but only for women with BRCA-positiveand homologous recombination deficient (HRD)-positive ovarian cancer. (Also see “GSK’s Zejula Wins First-Line Ovarian Cancer Use“—Scrip, 30 Apr, 2020.) [Corrected to reflect the types of cancer for which olaparib is approved.]
“Our portfolio is still smaller than that of many lead players, but we’re coming,” Hoos said. “I think you see that in terms of some of the success stories that we recently had.”
ADVANCES ACROSS FOUR KEYS CATEGORIES
The oncology R&D head explained that GSK’s cancer drug development strategy falls into four major categories, the first and largest of which is immuno-oncology – including belantamab mafodotin, dostarlimab, the inducible T-cell co-stimulator (ICOS) agonist GSK3359609 and several earlier clinical-stage candidates against TIM-3, LAG-3, OX40, STING and TLR4.
The ICOS agonist GSK3359609 already has shown promising activity in combination with Keytruda in recurrent or metastatic PD-1/L1 naive head and neck squamous cell carcinoma (HNSCC) patients, and more data from that open-label study were presented during ASCO. The overall response rate among 34 evaluable patients was 24 percent with eight patients responding, including four complete responses and four partial responses that were durable, lasting six months or more.
In terms of the other cancer drug categories important to GSK, Zejula is included in the synthetic lethality category because of PARP’s role in DNA repair.
In the company’s cell and gene therapy category, the T-cell receptor (TCR) therapy GSK3377794 targeting NY-ESO-1—developed in partnership with Adaptimmune Therapeutics PLC under a deal signed in 2014—has shown efficacy in synovial sarcoma and multiple myeloma. (Also see “$350m Adaptimmune deal shows GSK still does cancer R&D“—Scrip, 2 Jun, 2014.) GSK partnered with Lyell Immunopharma in October on its technology to improve T-cell function and fitness, which it planned to use initially to upgrade GSK3377794. (Also see “Deal Watch: GSK Furthers Cancer Gene Therapy Plans Via Lyell Collaboration“—Scrip, 10 Oct, 2019.)
“We have seen very good data in certain types of soft tissue sarcoma, in multiple myeloma and we’re now testing it in lung cancer,” Hoos said. “There will also be more data coming out this year, actually more substantive data. What I think is the most important to know about this program is it’s the very first cell therapy program across the entire industry that works in solid tumors.”
Being able to treat solid tumors effectively with a cell therapy is important to GSK, because solid tumors are a bigger market than hematological malignancies, making the NY-ESO-1-targeting TCR therapy more attractive commercially and in terms of being able to serve more patients. “That’s our aim—to access solid tumors through the cell therapy story that we’re building at GSK,” Hoos said. “So far, we’re industry-leading in that area, so we are quite excited about that.”
In cancer epigenetics, GSK’s fourth cancer drug development category, the company is