MedNess: bite-size biopharma and medtech news

Junshi Biosciences’ and Coherus’ Toripalimab receives Breakthrough Therapy Designation for 1L NPC
On 12^th August, Junshi Biosciences and Coherus announced that the US FDA has granted breakthrough therapy designation (BTD) to Toripalimab (PD-1 inhibitor) in combination with chemotherapy as a frontline treatment option for recurrent or metastatic nasopharyngeal carcinoma (NPC). The designation is based on results from the Phase 3 JUPITER-02 trial.
Background: NPC is a rare but aggressive cancer of the head and neck. It is often diagnosed at advanced stages and has a high relapse rate in early stage. Chemotherapy is the only frontline treatment available with gemcitabine + cisplatin (GC) as the preferred and Category 1 treatment as per the NCCN. Immunotherapy is used in subsequent treatment lines as a Category 2B recommendation.
Details: JUPITER-02 evaluated toripalimab + SoC chemotherapy (GC) vs. GC alone in 289 patients with either primary metastatic or recurrent NPC that is not amenable for local-regional or curative treatment.
At an interim analysis, the trial met the primary endpoint by showcasing a statistically significant improvement in PFS by BICR review (mPFS: 11.7 vs. 8.0 months, p=0.0003). PFS @ 1-year was 49% vs. 28% for toripalimab + GC vs. GC alone. Improvements in PFS were observed regardless of PD-L1 expression.
Key secondary points of ORR (77.4% vs.66.4%, p=0.034) and DoR (10.0 vs. 5.7 months, p=0.001) also demonstrated significant improvements with toripalimab. Although OS data was immature, a 40% risk reduction in death was observed in the toripalimab arm vs. GC alone arm (p_nominal=0.046). 1- and 2-year OS rates were 91.6% vs. 87.1% and 77.8% vs. 63.3%, respectively.
Grade ≥3 Immune mediated AEs were more frequent with toripalimab (7.5% vs. 0.7%), while Grade ≥3 TRAEs, fatal AEs and treatment discontinuations were similar across both arms.
Earlier, toripalimab monotherapy also received BTD form the FDA for recurrent or metastatic NPC following progression on or after platinum-containing chemotherapy.
Implications: In the US, currently there are no approved frontline treatments for NPC. In February 2021, Coherus collaborated with Junshi to co-develop and solely commercialize toripalimab in the US and Canada. Junshi and Coherus expects to complete the rolling submission of the BLA for both 1^st Line (+ chemotherapy) and 2^nd/ 3^rd Line (monotherapy) NPC later in Q3 2021.
Toripalimab is conditionally approved in China for NPC after failure of ≥2 prior lines of systemic therapy and is under review for 1L treatment.

FDA Approves LENVIMA + KEYTRUDA Combination for 1L Treatment of Adult Patients With Advanced RCC
“This approval is based in part on data demonstrating that KEYTRUDA plus LENVIMA significantly reduced the risk of disease progression or death versus sunitinib,” said Dr. Robert Motzer, Jack and Dorothy Byrne Chair in Clinical Oncology, Kidney Cancer Section Head, Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center. “This is a significant milestone for newly diagnosed patients with advanced renal cell carcinoma and introduces a promising combination option in the first-line setting.”

FDA Grants Priority Review to sBLA for KEYTRUDA as Adjuvant Therapy in Certain Patients With RCC Following Surgery
 “The acceptance of our application demonstrates the progress we are making in earlier lines and earlier stages of certain cancers across our oncology portfolio,” said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. “We look forward to working with the FDA towards the goal of bringing the first adjuvant immunotherapy option to appropriate patients with renal cell carcinoma in the U.S.”

Clinical Hold on Eprenetapopt Lymphoid Malignancy Program Announced

• FDA placed a clinical hold on clinical trial evaluating eprenetapopt with acalabrutinib or with venetoclax and rituximab in lymphoid malignancies.
• No additional patients can be enrolled until the clinical hold is resolved, though patients on study deriving clinical benefit can continue to receive study treatment.
• Subsequent to receiving notification of a partial clinical hold on myeloid malignancies program, FDA placed a clinical hold on lymphoid malignancy study.
• The FDA’s concerns referred to the safety and efficacy data from the Phase 3 MDS clinical trial.
• One CLL patient is currently on study treatment receiving eprenetapopt in combination with venetoclax and rituximab and has achieved complete remission (CR).