Category: 3. Business

After 6 years of follow-up, toripalimab-tpzi (Loqtorzi) plus chemotherapy maintained its survival advantage over chemotherapy alone in patients with recurrent or metastatic nasopharyngeal carcinoma (NPC), according to long-term overall survival (OS) findings from the phase 3 JUPITER-02 study (NCT03581786).¹

In this exploratory post-hoc analysis, findings from which were presented at the 2025 ESMO Asia Congress, patients treated with toripalimab plus gemcitabine and cisplatin achieved a median OS of 64.8 months vs 33.7 months with chemotherapy alone. This translated to a 31-month improvement and a 38% reduction in the risk of death (HR 0.62; 95% CI, 0.45-0.85). Coherus Oncology, the drug’s developer, stated that these results reinforce the regimen’s role in the recurrent/metastatic setting.

“The new 6-year overall survival follow-up data give us even greater confidence to use toripalimab in patients with NPC that is recurrent or metastatic,” Victoria Villaflor, MD, professor and director of the Head and Neck Oncology Program in the Division of Hematology-Oncology, Department of Medicine, at the University of California Irvine School of Medicine, stated in a news release.

“These data suggest a significant long-term OS benefit for patients living with [recurrent/metastatic] NPC,” Rosh Dias, MD, chief medical officer of Coherus Oncology, added in the news release. “With these long-term data, [toripalimab] in combination with chemotherapy, reinforces the data supporting this regimen as the standard of care for patients living with [recurrent/metastatic] NPC.”

What was the design of JUPITER-02?

The JUPITER-02 was a randomized, double blind, placebo-controlled study that evaluated the addition of PD-1 blockade to standard chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma.

The trial enrolled 289 patients with metastatic or recurrent, locally advanced NPC who had not received previous systemic chemotherapy for recurrent or metastatic disease.² Patients were randomly assigned 1:1 to receive toripalimab at 240 mg every 3 weeks or the corresponding dose of placebo before receiving chemotherapy every 3 weeks for up to 6 cycles, followed by either toripalimab or placebo maintenance for up to 2 years.^2,3 The chemotherapy regimen included 1,000 mg/m² of administered intravenous (IV) gemcitabine administered on days 1 and 8 and 80 mg/m² of IV cisplatin on day 1 of each cycle.

The primary end point was progression-free survival (PFS) according to RECIST 1.1 criteria.² Key secondary end points included OS, overall response rate, disease control rate, duration of response, and safety.

What prior data have been reported from this trial?

In JUPITER-02, the combination reduced the risk of disease progression or death by 48% vs chemotherapy alone (HR, 0.52; 95% CI, 0.36-0.74; P < .0003).⁴ The median PFS was 11.7 months (95% CI, 11.0–not evaluable [NE]) in the combination arm (n = 146) vs 8.0 months (95% CI, 7.0-9.5) in the control arm (n = 143).² The median OS was not reached (95% CI, 38.7 months, not estimable) with the toripalimab combination vs 33.7 months (95% CI, 27.0, 44.2) with chemotherapy alone (95% CI, 27.0-44.2).⁴ This translated to a 37% reduction in the risk of death vs chemotherapy alone (HR, 0.63; 95% CI, 0.45-0.89; P = .0083).

These results supported the 2023 FDA approval of toripalimab in combination with cisplatin and gemcitabine for the first-line treatment of adult patients with metastatic or recurrent locally advanced nasopharyngeal carcinoma.² The FDA also approved toripalimab as monotherapy for patients with recurrent unresectable or metastatic NPC who progressed on or after platinum- containing chemotherapy based on findings from the phase 2 POLARIS-02 trial (NCT02915432).

What are the key safety considerations for toripalimab plus chemotherapy?

Toripalimab is often associated with immune-mediated adverse effects (AEs) such as pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, and skin adverse reactions.¹

The most frequently observed (≥ 20%) AEs with toripalimab plus chemotherapy included nausea, vomiting, decreased appetite, constipation, hypothyroidism, rash, pyrexia, diarrhea, peripheral neuropathy, cough, musculoskeletal pain, upper respiratory infection, insomnia, dizziness, and malaise.

References

1. Coherus announces six-year JUPITER-02 follow-up results showing LOQTORZI plus chemotherapy nearly doubles median overall survival in nasopharyngeal carcinoma. News release. Coherus. December 8, 2025. Accessed December 8, 2025. https://investors.coherus.com/news-releases/news-release-details/coherus-announces-six-year-jupiter-02-follow-results-showing
2. The efficacy and safety study of toripalimab injection combined with chemotherapy for nasophapyngeal cancer. ClinicalTrials.gov. Updated September 2, 2025. Accessed December 8, 2025. https://www.clinicaltrials.gov/ct2/show/NCT03581786
3. FDA approves toripalimab-tpzi for nasopharyngeal carcinoma. FDA. October 27, 2023. Accessed December 8, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-toripalimab-tpzi-nasopharyngeal-carcinoma
4. Coherus and Junshi Biosciences announce FDA approval of Loqtorzi (toripalimab-tpzi) in all lines of treatment for recurrent or metastatic nasopharyngeal carcinoma (NPC). News release. Coherus BioSciences and Shanghai Junshi Biosciences. October 27, 2023. Accessed December 8, 2025. https://investors.coherus.com/news-releases/news-release-details/coherus-and-junshi-biosciences-announce-fda-approval-loqtorzitm

Results from the ongoing phase 1/2 ATALANTA-1 trial (CTIS: 2022-502661-23-00; NCT06561425) indicate that GLPG5101, a novel CD19-targeted chimeric antigen receptor (CAR) T-cell therapy, demonstrated a manageable safety profile and notable efficacy results in patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) including mantle cell lymphoma (MCL).^1,2

Results from the MCL cohort were announced at the 2025 ASH Annual Meeting by Marie Jose Kersten, MD, PhD, professor of hematology at Amsterdam UMC, on December 7, 2025.¹ Previous results were published in Blood on November 5, 2024.²

The therapy showed high and durable antitumor activity across the studied NHL subtypes. In the R/R MCL patient cohort (n = 24), at 9.1 months’ median follow-up, all the patients achieved an overall response, and the complete response (CR) rate was 95.8%.¹

The therapy is distinguished by its use of a fresh, stem-like, early memory T-cell phenotype and a rapid, decentralized manufacturing platform that enables a 7-day vein-to-vein time.

Efficacy was evaluated in 42 patients who had reached the first response assessment. The objective response rate (ORR) was 88% (n = 37/42).² The CR rate was 83% (n = 35/42). Of 11 responding patients in phase 1 of the study, 10 had an ongoing response at the data cutoff and 1 patient completed the study while in CR. In phase 2 of the study, all 21 patients had an ongoing response at the data cut off. Of the total patients, 4 (3 with diffuse large B-cell lymphoma [DLBCL] and 1 with MCL) experienced progression after achieving an initial response.

GLPG5101 demonstrated robust expansion in the body across all tested dose levels and disease indications. Persistent CAR T-cells were detected in peripheral blood for up to 21 months post-infusion, indicating long-term durability.

Minimal residual disease (MRD) negativity in plasma was achieved in 12 of 15 (80%) evaluable patients who had achieved a CR. Crucially, all 11 MRD-negative patients with a minimum of 6 months follow-up remained in ongoing CR at the time of data cut off, linking deep molecular remission to durable clinical benefit.

In the R/R MCL cohort, 90% (n = 9/10) of MRD-evaluable patients were MRD-negative at CR. Additionally, 7 of the 9 MRD-negative patients remained in CR at the time of the data cut off.¹

Safety Profile of GLPG5101

GLPG5101 demonstrated a manageable safety profile with low incidence of high-grade toxicities in the MCL cohort. The reported data reflects treatment-emergent adverse events (TEAEs) reported up to 14 weeks post-infusion.

In phases 1 and 2, any grade cytokine release syndrome (CRS) occurred in 9 vs 10 patients. Grade 3 or higher CRS occurred in 1 vs 0 patients. Any grade immune effector cell–associated neurotoxicity syndrome (ICANS) occurred in 6 vs 4 patients, and grade 3 or higher ICANS occurred in 0 vs 1 patients.

The most frequently reported TEAEs of grade 3 or higher were hematologic. Out of 49 infused patients, 2 died during the treatment period and 1 died during follow-up.

Study Design and Patient Characteristics

This is an ongoing phase 1/2 study designed to evaluate the safety and efficacy of GLPG5101.

The primary objectives of phases 1 and 2 are to establish the safety, determine the recommended phase 2 dose, and to evaluate the efficacy of GLPG5101. The secondary objectives are to assess manufacturing feasibility, further safety parameters, and additional efficacy metrics such as duration of response and MRD.

The ATALANTA-1 trial enrolled heavily pretreated adult patients with various subtypes of R/R NHL. Patients had a median of 2 prior systemic therapies. Eligible indications included DLBCL, MCL, follicular lymphoma, marginal zone lymphoma, Burkitt lymphoma, and primary central nervous system lymphoma.

In the MCL cohort, the median age of patients in phase 1 was 66.5 years (range, 25–78), and 67 years (range, 40–81) in phase 2. The median range of prior therapies between both phases was 2.5 (range, 1–7) vs 3 (range, 2–11). The majority of patients had received prior Bruton tyrosine kinase inhibitor.¹

As of the data cutoff, 53 patients had undergone leukapheresis, 49 received an infusion, and 47 of the 49 patients received fresh product. In the R/R MCL cohort, 25 patients received CAR T-cell infusion, with 24 patients receiving fresh product.

A 7-day vein-to-vein time was successfully achieved in 43 of the 47 patients (91%) who received the fresh product. In the R/R MCL cohort specifically, 23 of 24 patients achieved a 7-day vein-to-vein time. Short vein-to-vein time eliminated the need for cytotoxic bridging therapy for all patients who received a fresh product.

The final product demonstrated significant enrichment of desired T-cell phenotypes compared to the starting material. The proportion of early T-cell phenotypes (naive/stem cell memory and central memory) was significantly increased in both CD4+ and CD8+ CAR T cells. A median increase in the CD4:CD8 ratio of CAR+ T cells was observed in the final product.

In August 2025, GLPG5101 received a regenerative medicine advanced therapy designation in MCL from the FDA based on preliminary clinical data.³

The interim results from the ATALANTA-1 study provide strong evidence for the potential of GLPG5101 as a novel CAR T-cell therapy for R/R NHL. The rapid, 7-day vein-to-vein manufacturing time is a significant logistical advantage that can accelerate access to treatment for patients with urgent clinical needs.^.

“In conclusion, in the ATALANTA-1 study, we saw deep and durable responses in patients with MCL, including patients with high-risk features, of course with relatively short follow-up,” concluded Kersten during the presentation.¹ “And we saw…a 96% CR in patients with high-risk disease and a duration of response at 9 months of 83%. We have a very favorable safety profile, no grade 3 or higher CRS and only 1 patient with grade 3 ICANS. We would feel very comfortable even in [patients with MCL] to deliver this therapy on an outpatient basis…All in all, we think this product should be further developed.”

REFERENCES

1. Kersten M, Vermaat J, Mutsaers P, et al. High complete response rates and minimal residual disease (MRD) negativity, with durable responses, in high-risk mantle cell lymphoma (MCL) with GLPG5101, a fresh, early memory-enriched CAR T-cell therapy with a 7-day vein-to-vein time: Results from the ATALANTA-1 MCL cohort. Presented at: 2025 ASH Annual Meeting; December 7, 2025; Orlando, Florida. Abstract 662.

2. Kersten M, Saevels K, Willems E, et al. ATALANTA-1: A phase 1/2 trial of GLPG5101, a fresh, stem-like, early memory CD19 CAR T-cell therapy with a 7-day vein-to-vein time, for the treatment of relapsed/refractory non-Hodgkin lymphoma. Blood. 2024;144(suppl 1):93. doi:10.1182/blood-2024-205360.

3. Galapagos NV announces U.S. FDA Regenerative Medicine Advanced Therapy (RMAT) designation granted to GLPG5101 for the treatment of relapsed/refractory mantle cell lymphoma. News release. Galapagos NV. Published February 10, 2025. Accessed August 12, 2025. https://tinyurl.com/vkvnfvps

The first-in-class mutant calreticulin (CALR)–targeted monoclonal antibody INCA033989 has been granted breakthrough therapy designation by the FDA for the treatment of patients with essential thrombocythemia harboring a type 1 CALR mutation who are resistant or intolerant to at least 1 cytoreductive therapy.¹

Data from the phase 1 INCA033989-101 (NCT05936359) and INCA033989-102 (NCT06034002) trials supported the designation. Findings from the trials presented during the 2025 European Hematology Association Congress demonstrated that no dose-limiting toxicities (DLTs) were reported in patients treated across dose levels (n = 49) and the maximum tolerated dose was not reached.² At the data cutoff, most patients remained on treatment (98%) and the median duration of treatment exposure was 22.6 weeks (range, 0.6-69.2%). Updated results from the studies are planned to be presented during the 2025 ASH Annual Meeting.¹

“Incyte has long been committed to improving outcomes for patients with MPNs, and this Breakthrough Therapy designation underscores the potential of INCA033989 to be a novel therapy that could significantly transform the treatment of patients [with] essential thrombocythemia, who today have limited treatment options,” Pablo J. Cagnoni, MD, president and head of research and development at Incyte, stated in a news release. “The designation allows us to expedite the development pathway for INCA033989 in patients with type 1 mutations.”

How were these phase 1 studies designed?

The essential thrombocytopenia cohort of INCA033989-101 and INCA033989-102 trials enrolled patients with a diagnosis of essential thrombocytopenia per 2022 World Health Organization criteria.² Patients also needed to have disease harboring a CALR exon 9 mutation, documented resistance or intolerance to at least 1 previous line of cytoreductive therapy, a platelet count of more than 450 × 10⁹/L, and high-risk disease. High-risk disease was defined as being at least 60 years old, having a history of thrombosis, history of major bleeding without any clearly documented alternative explanation, or extreme thrombosis.

INCA033989-101 enrolled patients outside the US and INCA033989-102 was a US-only study. Patients received intravenous INCA033989 every 2 weeks at doses ranging from 24 mg to 2500 mg.

The primary end points were the incidences of DLTs and treatment-emergent adverse effects (TEAEs). Secondary end points included response rate per European LeukemiaNet criteria, symptom improvement per the Myeloproliferative Neoplasm Symptom Assessment Form total symptom score, changes in allele burden of mutant CALR, and pharmacokinetic measures.

What additional safety and efficacy data have been reported with INCA033989?

Additional findings from these studies showed that the best overall response rates among patients treated at the 24-mg to 250-mg dose levels were 80% and 86%, respectively. Respective complete response (CR) rates were 68% and 82% in patients who were treated in the 400-mg to 2500-mg dose range.

Most evaluable patients (89%; n = 34/38) achieved a reduction in the variant allele frequency (VAF) of mutant CALR. Forty-seven percent of these patients experienced a reduction of more than 20% of mutant CALR VAF, and 21% achieved a greater than 50% reduction. A reduction of at least 20% of mutant CALR VAF occurred within 6 cycles for all 18 responders, and all molecular responders achieved a hematological response of either a CR or a partial response.

Further safety data revealed that any-grade TEAEs occurred at a rate of 85.7%, including treatment-related (61.2%), grade 3 or higher (26.5%), and serious (6.1%) TEAEs. Treatment discontinuation (2.0%) and dose reduction (2.0%) due to TEAEs also occurred. Most TEAEs were grade 1 to 2 in severity and the most frequent grade 3 or higher TEAE was a transient increase in asymptomatic lipase levels (6.1%).

“Looking ahead, we plan to initiate a phase 3 program evaluating INCA033989 in patients [with] essential thrombocythemia with all types of CALR mutations in mid-2026, following alignment with regulators in the first half of next year,” Cagnoni noted in the news release.¹

References

1. Incyte’s first-in-class mutCALR-targeted monoclonal antibody, INCA033989, granted breakthrough therapy designation by U.S. FDA. News release. Incyte. December 7, 2025. Accessed December 8, 2025. https://incytecorp.gcs-web.com/news-releases/news-release-details/incytes-first-class-mutcalr-targeted-monoclonal-antibody
2. Mascarenhas J, Ali H, Yacoub A, et al. INCA33989 is a novel, first-in-class, mutant calreticulin-specific monoclonal antibody that demonstrates safety and efficacy in patients with essential thrombocythemia (ET). Presented at: 2025 European Hematology Association Congress; June 12-15, 2025; Milan, Italy. Abstract LB4002