Oncology Weekly Report: Jan 8-14, 2024

Breast Cancer

The TORCHLIGHT Trial was a double-blinded Phase 3 trial that evaluated the combination of toripalimab and nab-paclitaxel in 531 patients with metastatic or recurrent triple-negative breast cancer TNBC (1). The study showed significant improvement in progression-free survival in the experimental arm, particularly in PD-L1-positive patients.

The FUTURE-SUPER Trial was a Phase 2 multi-cohort, randomised, controlled trial that studied subtyping-based therapy in 139 patients with metastatic or recurrent triple-negative breast cancer (2). The study reported longer progression-free survival in the subtyping-based group compared to controls.

Glioblastoma

A Phase 1 trial focused on the safety and efficacy of carcinoembryonic antigen-expressing oncolytic measles virus derivative (MV-CEA) in 22 patients with recurrent glioblastoma (3). The trial reported good tolerance, no dose-limiting toxicity, and a median overall survival of 11.6 months. Notably, the one-year survival rate was 45.5%, and the study highlighted the potential of oncolytic MV derivatives for further clinical investigation.

Gastric and gastroesophageal junction adenocarcinoma

The Panda Trial was a Phase 2 clinical trial that assessed neoadjuvant atezolizumab plus chemotherapy in 21 patients with gastric and gastroesophageal junction adenocarcinoma (4). The trial reported a high rate of major pathologic response and a significant difference in immune cell infiltration between responders and non-responders.

Pancreatic and Colorectal Cancers

The phase 1 AMPLIFY-201 trial investigated a lymph-node-targeted, mKRAS-specific amphiphile vaccine, ELI-002 2P, in 25 patients with pancreatic and colorectal cancers and found significant T cell responses and biomarker reduction, suggesting its efficacy in immunotherapy-recalcitrant KRAS-mutated tumors (5).

Chronic Lymphocytic Leukemia, B-cell Non-Hodgkin Lymphoma

A first-in-human Phase 1 trial evaluated nemtabrutinib, a reversible inhibitor of Bruton tyrosine kinase (BTK) and C481S mutant BTK, in 47 patients with relapsed/refractory hematologic malignancies (6). The study found a high incidence of grade ≥3 adverse events but demonstrated an overall response rate of 75% in CLL patients at the recommended phase II dose.

Peripheral T-cell lymphoma (PTCL)

A first-in-human Phase 1 study evaluated EZH2 inhibitor SHR2554 in 28 patients with relapsed or refractory peripheral T-cell lymphoma. The study reported a promising response rate and a manageable safety profile (7).

Follicular Lymphoma

The Phase II ELARA trial investigated tisagenlecleucel in 97 patients with relapsed/refractory follicular lymphoma and found highly durable efficacy and a favorable safety profile, with high complete response rates and no new safety signals (8).

High-risk Neuroblastoma

A Phase 1 trial established the maximum tolerated dose of DFMO in combination with celecoxib, cyclophosphamide, and topotecan for patients with relapsed neuroblastoma (9). The study enrolled 24 patients aged 2 to 30 years with relapsed/refractory high-risk neuroblastoma. The primary outcome focused on the objective response rate and progression-free survival. The study concluded that this combination therapy demonstrated a manageable safety profile and promising antitumor activity.

Advanced/Metastatic Melanoma

The SAFFRON-103 study, a Phase Ib trial, investigated the efficacy and safety of sitravatinib in combination with tislelizumab in patients with unresectable, advanced, or metastatic melanoma (10). The study enrolled 25 patients who had previously shown disease progression on anti-PD-(L)1 monotherapy. The primary endpoint was safety and tolerability, with treatment-emergent adverse events being a key focus. The study concluded that the combination of sitravatinib and tislelizumab demonstrated manageable safety and tolerability profiles in this patient population.

Melanoma

A Phase I study investigated the effect of a novel immunotherapeutic approach in 8 patients with refractory advanced melanoma and found that the treatment was well-tolerated and showed promising early results, including a 50% complete response rate in injected lesions (11).

Non-Small-Cell Lung Cancer 

A registrational Phase 1-2 trial investigated the effect of repotrectinib in patients with ROS1 fusion-positive non-small-cell lung cancer and found durable clinical activity with manageable adverse events, particularly in patients who had not previously received a ROS1 tyrosine kinase inhibitor (12).

References

  1. Jiang Z, Ouyang Q, Sun T, Zhang Q, Teng Y, Cui J, et al. Toripalimab plus nab-paclitaxel in metastatic or recurrent triple-negative breast cancer: a randomized phase 3 trial. Nat Med. 2024.

  2. Fan L, Wang ZH, Ma LX, Wu SY, Wu J, Yu KD, et al. Optimising first-line subtyping-based therapy in triple-negative breast cancer (FUTURE-SUPER): a multi-cohort, randomised, phase 2 trial. Lancet Oncol. 2024.

  3. Galanis E, Dooley KE, Keith Anderson S, Kurokawa CB, Carrero XW, Uhm JH, et al. Carcinoembryonic antigen-expressing oncolytic measles virus derivative in recurrent glioblastoma: a phase 1 trial. Nat Commun. 2024;15(1):493.

  4. Verschoor YL, van de Haar J, van den Berg JG, van Sandick JW, Kodach LL, van Dieren JM, et al. Neoadjuvant atezolizumab plus chemotherapy in gastric and gastroesophageal junction adenocarcinoma: the phase 2 PANDA trial. Nat Med. 2024.

  5. Pant S, Wainberg ZA, Weekes CD, Furqan M, Kasi PM, Devoe CE, et al. Lymph-node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: the phase 1 AMPLIFY-201 trial. Nat Med. 2024.

  6. Woyach JA, Stephens DM, Flinn IW, Bhat SA, Savage RE, Chai F, et al. First-in-Human Study of the Reversible BTK Inhibitor Nemtabrutinib in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia and B-Cell Non-Hodgkin Lymphoma. Cancer Discov. 2024;14(1):66-75.

  7. Song Y, Jin Z, Li ZM, Liu Y, Li L, He C, et al. Enhancer of zeste homolog 2 inhibitor SHR2554 in relapsed or refractory peripheral T-cell lymphoma: data from the first-in-human phase 1 study. Clin Cancer Res. 2024.

  8. Dreyling M, Fowler NH, Dickinson M, Martínez-López J, Kolstad A, Butler J, et al. Durable Response After Tisagenlecleucel in Adults With Relapsed/Refractory Follicular Lymphoma: ELARA Trial Update. Blood. 2024.

  9. Hogarty MD, Ziegler DS, Franson A, Chi YY, Tsao-Wei D, Liu K, et al. Phase 1 study of high-dose DFMO, celecoxib, cyclophosphamide and topotecan for patients with relapsed neuroblastoma: a New Approaches to Neuroblastoma Therapy trial. Br J Cancer. 2024.

  10. Wang X, Pan H, Cui J, Chen X, Yoon WH, Carlino MS, et al. SAFFRON-103: a phase Ib study of sitravatinib plus tislelizumab in anti-PD-(L)1 refractory/resistant advanced melanoma. Immunotherapy. 2024.

  11. Tijtgat J, Geeraerts X, Boisson A, Stevens L, Vounckx M, Dirven I, et al. Intratumoral administration of the immunologic adjuvant AS01(B) in combination with autologous CD1c (BDCA-1)(+)/CD141 (BDCA-3)(+) myeloid dendritic cells plus ipilimumab and intravenous nivolumab in patients with refractory advanced melanoma. J Immunother Cancer. 2024;12(1).

  12. Drilon A, Camidge DR, Lin JJ, Kim SW, Solomon BJ, Dziadziuszko R, et al. Repotrectinib in ROS1 Fusion-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2024;390(2):118-31.