Near-Term Oncology Pipeline Review: Expect More Agents Targeted to Small Patient Populations

January 2022 Vol 13, No 1


Oncology Pipeline

A number of innovative therapies in oncology have made it to market recently, with a wealth of products on the verge of approval. With 75% of pharmaceutical research and development focused on cancer and oncology, a panel moderated by Doug Long, vice president, Industry Relations at IQVIA, discussed cancer pharmaceutical trends and explored the near-term innovative agents coming to market.

The US oncology therapeutics market has reached $71 billion. While COVID-19 has slowed the growth of sales, total growth in the oncology market is being driven by the targeted oncology category, said Mr Long. COVID has not had an impact on the number of launches in the oncology space, as 2020 and 2021 have seen similar rates of product launches as 2019.

Dipti Shah, PharmD, senior clinical program manager at CVS Specialty, provided an overview of the oncology therapeutics landscape, highlighting a handful of especially innovative products, some in niche areas.

Recently Approved Agents

In 2021, tivozanib received FDA approval for the treatment of relapsed/refractory (R/R) renal-cell carcinoma (RCC). Although an improvement in progression-free survival was demonstrated with tivozanib compared with sorafenib in patients with advanced RCC, overall survival data favored sorafenib, she observed.

Umbralisib was granted FDA approval for the treatment of marginal-zone lymphoma (MZL). About 7500 patients per year are diagnosed with MZL. “An additional therapy in this space is going to give patients choice, especially with its good side effect profile in clinical trials,” she said.

Tepotinib gained approval for the treatment of metastatic non–small-cell lung cancer (NSCLC) harboring MET exon 14 skipping alterations. Only about 3% to 4% of patients with NSCLC have such alterations, but their prognosis is poor, said Dr Shah.

Lisocabtagene maraleucel is a gene therapy that was approved for the treatment of R/R large B-cell lymphoma (BCL). In the single-arm, open-label TRANSCEND trial conducted in patients with R/R BCL, the overall response rate with lisocabtagene was 73%. Of the 104 patients who achieved a complete response, 65% had remission lasting at least 6 months, and 62% had remission lasting at least 9 months. Ten-year follow-up with these patients will be very important and will ultimately be the driver of value behind these therapies, said panelist Cheryl Allen, PharmD, executive vice president, Industry Relations & Business Development, Asembia.

Sotorasib is an oral therapy that targets KRAS, approved for the treatment of patients with KRAS G12C–mutated NSCLC. “It is important to note that KRAS has multiple biomarkers within itself,” said Dr Shah. “Only those patients with a G12C mutation will respond to this therapy.” This type of mutation represents <3% of patients with NSCLC, she said.

Mobocertinib is an oral tyrosine kinase inhibitor that was approved for the treatment of EGFR exon 20 insertion–positive metastatic NSCLC. EGFR exon 20 insertion mutations occur in 4% to 12% of EGFR-mutated NSCLCs and approximately 2% of all NSCLCs.

Pipeline Agents

Dr Shah highlighted 3 oncolytics (pacritinib, ublituximab, and magrolimab) expected to gain FDA approval in late 2021 or 2022, and another is expected to gain a new indication (nivolumab).

Pacritinib is an oral macrocyclic Janus kinase (JAK) inhibitor that is being developed for the treatment of myelofibrosis and may represent a good option in patients with severe thrombocytopenia, said Dr Shah. Its unique mechanism of action, inhibiting JAK2 and IRAK1 without inhibiting JAK1, may reduce the risk of cytopenias and immune dysfunction associated with other JAK inhibitors.

A biologics license application was accepted by the FDA for the CD20-directed monoclonal antibody ublituximab (in combination with umbralisib) for the treatment of patients with chronic lymphocytic leukemia and small lymphocytic leukemia. Expected approval is March 2022.

An application for the use of nivolumab in combination with ipilimumab or chemotherapy in the first-line setting for patients with unresectable advanced, recurrent, or metastatic esophageal squamous-cell carcinoma (ESCC) was accepted by the FDA.

The filings were based on results from the pivotal phase 3 CheckMate-648 trial, in which nivolumab plus ipilimumab and nivolumab plus chemotherapy demonstrated a statistically significant and clinically meaningful benefit in overall survival compared with chemotherapy in patients with unresectable advanced or metastatic ESCC with tumor cell PD-L1 expression ≥1% as well as in the all-randomized population. Expected approval is May 2022.

Magrolimab is an anti-CD47 monoclonal antibody being studied in combination with azacitidine as first-line treatment for patients with intermediate-, high-, or very high-risk myelodysplastic syndrome. The combination showed a complete response of 42% compared with 20% for azacitidine monotherapy in a phase 1b trial. Approval is expected in the third quarter of 2022.

Tremendous Unmet Need

“Despite amazing new drugs, some patients aren’t benefiting sufficiently or at all. There’s still tremendous unmet need in oncology, which is why the huge pipeline of activity,” said Jeffrey Bockman, PhD, executive vice president, Head of Oncology Practice, Cello Health BioConsulting. That pipeline is filled with a plethora of nonimmuno-oncologic targeted agents, but immuno-oncology and precision medicine are driving pipeline value, he said.

Clinical benefit (aka, value), not simply price, is becoming a focus even for early-stage drug developers, said Dr Bockman, especially so for multicomponent high-priced immuno-oncology regimens.

Dr Allen made a case for value-based oncology determinations with the increase in innovation.

Right now, much of the cost of therapy is the payers’ burden, and the patient is generally not involved. Manufacturer financial support is limited to commercially insured patients.

To make better decisions with increased competition in the oncology space, “head-to-head studies are needed to see what this will do ultimately for the payer base,” she said.

Last modified: August 10, 2023

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