Jazz Pharmaceuticals wasn’t able to ride a breakthrough FDA nod to a pivotal trial win for conditionally approved small cell lung cancer (SCLC) drug Zepzelca. But after talking with the FDA, the company and partner PharmaMar see a new path forward.
In previously treated SCLC, the combination of Zepzelca and doxorubicin failed to extend patients’ lives over physician’s choice of doxorubicin-based chemo or Hycamtin, according to data presented at the 2021 World Conference on Lung Cancer virtual meeting.
Jazz and PharmaMar first unveiled the phase 3 ATLANTIS failure in December. Now we know patients who mostly got the Zepzelca regimen as their second-line treatment lived a median 8.6 months, versus 7.6 months in the control arm.
If successful, the trial could have served as the confirmatory trial to convert Zepzelca’s accelerated approval earned last June into a full one. In a previous single-arm study, Zepzelca monotherapy shrunk tumors in 35% of relapsed SCLC patients as measured by investigator assessment. The response lasted a median 5.3 months.
Pascal Besman, chief operating officer at PharmaMar, noted that the ATLANTIS study used a 2-mg/m2 dose of Zepzelca, which is lower than the FDA-approved dose of 3.2-mg/m2. Although the Zepzelca-doxorubicin combo didn’t improve survival, “the overall results support the activity and tolerability of Zepzelca monotherapy in second-line therapy,” Besman said in an email interview.
As ATLANTIS investigator Luis Paz-Ares, M.D., Ph.D., noted in a prepared presentation, the research team ran a so-called exposure-response analysis to gauge Zepzelca’s contribution on patient survival. The model predicted that single-agent Zepzelca, at the 3.2-mg/m2 dose, would have had a statistically significant advantage over the control arm at prolonging the lives of patients in the ATLANTIS study.
Jazz stands “firmly behind the favorable benefit/risk profile of monotherapy Zepzelca” in second-line SCLC as shown in its phase 2 trial, the company’s chief medical officer, Rob Iannone, M.D., said in a separate email interview.
For now, Zepzelca will remain on the market. Jazz and PharmaMar have agreed “in principle” with the FDA to run another phase 3 as the confirmatory trial, Besman said.
The three-arm trial will test Zepzelca monotherapy at 3.2 mg/m2, and a second experimental arm will combine the drug at 2 mg/m2 with Pfizer’s Camptosar (irinotecan).
Second-line patients in the control arm will get physician’s choice or either Camptosar or Hycamtin. The trial, expected to launch this year, will also support a regulatory filing to the European Medicines Agency, Besman added.
In addition, Jazz is collecting data from an observational phase 4 trial to understand Zepzelca’s real-world profile in second-line SCLC, Iannone noted.
Meanwhile, Jazz is also looking to move Zepzelca earlier in the treatment line. Through a partnership with Roche, a phase 3 trial dubbed ImForte will test Zepzelca with immunotherapy as a first-line maintenance therapy for patients with extensive-stage SCLC after induction chemotherapy. If successful, the new regimen could pressure AstraZeneca and its Imfinzi, which is currently dominating the front-line SCLC space.