- Jounce Therapeutics' stock fell to a 52-week low Monday as shaky efficacy data from a Phase 1/2 trial of the biotech's lead drug weighed on the company's share price.
- The ICONIC trial is ongoing, testing Jounce's JTX-2011 alone and in combination with Bristol-Myers Squibb's Opdivo for treating solid tumors. But early results presented at the American Society of Clinical Oncology's annual meeting showed few participants experienced partial response (PR) when put on either regimen.
- In the Phase 1 portion, one of four gastric cancer (GC) patients receiving the monotherapy registered a PR. And in Phase 2, one in 28 gastric cancer patients and one in 17 triple negative breast cancer (TNBC) patients on the combo therapy had PRs. Less than half of GC, TNBC, and head and neck squamous cell cancer (HNSCC) patients for whom data was available by the April 4 cutoff date achieved disease control.
Cancer drug companies are investing heavily in combination therapies, hoping their products will prove more safe or effective by pairing them with another treatment. The results of these experiments have been mixed.
Merck & Co., for instance, wowed the ASCO crowds again this year with data showing the risk of disease progression or death for squamous non-small cell lung cancer (NSCLC) patients declined 36% when Keytruda (pembrolizumab) was given with chemotherapy. AbbVie also posted evidence that combining its products Imbruvica (ibrutinib) and Venclexta (venetoclax) has a positive effect on minimal residual disease in a couple types of blood cancer.
But — as data from the weekend illustrates — the clinic has provided plenty of misfires, too. Incyte is a cautionary tale here, as the closely watched ECHO-301 study demonstrated a combo of the biotech's IDO inhibitor epacadostat plus Keytruda performed almost identically to treatment with just Keytruda in advanced melanoma patients.
Early signs are suggesting Jounce's compound could join this latter group too. In the Phase 2, dose-expansion portion of its study, researchers observed disease control in mostly small portions of the various cancer groups: 10 of 28 GC patients; three of 17 TNBC patients; two of 16 HNSCC patients and seven of 12 NSCLC patients.
(Notably, all the HNSCC and NSCLC patients in the data analysis previously failed PD-1 inhibitor therapy. The GC and TNBC patients were PD-1 inhibitor therapy naive, yet around 50-60% of the GC monotherapy, GC combo and TNBC combo groups received at least three prior treatments.)
Tumor shrinkage was observed in eight of the 28 Phase 2 GC patients treated with JTX-2011 plus Opdivo (nivolumab). The rates for the three other groups — TNBC, HNSCC and NSCLC — clocked in respectively at two in 17, one in 16 and four in 12.
Despite the rough start, Jounce intends to forge ahead with ICONIC, including initiating two other dose-escalation cohorts within the trial that would combine JTX-2011 with either Bristol-Myers' Yervoy (ipilimumab) or Keytruda.
"The new ipilimumab combination cohort may enable Jounce to explore a new combination mechanism that is supported by clinical and pre-clinical research," the biotech said in a June 2 statement. "Exploration with pembrolizumab at its approved q3w dose and schedule may allow the Company to evaluate JTX-2011 in combination with a PD-1 inhibitor in earlier lines of therapy."
Jounce shares sunk more than 30% in mid-May upon the release of an abstract detailing some of the data from ICONIC. Investors clearly remained displeased following an ASCO presentation that gave a more complete picture of the trial's early results. Company shares fell an additional 38% on Monday to trade at a year-long low of $6.92 apiece.
Less clear is how the fresh data will affect Jounce's partnership with Celgene, which paid $225 million upfront in July 2016 to secure exclusive options to develop and commercialize JTX-2011 — as well as up to four early-stage programs for B cell, T regulatory cell and tumor-associated macrophage targets. JTX-2011 is a monoclonal antibody that activates a T cell surface protein called inducible T cell co-stimulator.