01/05/2024 Oncology Daily Report

Lymphomas

One study was located; a phase 1b/2 trial that investigated polatuzumab vedotin combined with rituximab and lenalidomide (Pola+R+Len) in patients with relapsed or refractory diffuse large B-cell lymphoma and found that, while the treatment did not meet the prespecified activity threshold, it showed a tolerable safety profile and provided clinical benefit to some patients (1). The study enrolled 57 patients, with a complete response rate of 31% and common adverse events including neutropenia (61%) and thrombocytopenia (14%).

Reference

  1. Abrisqueta P, González-Barca E, Panizo C, Pérez JMA, Miall F, Bastos-Oreiro M, Triguero A, Banerjee L, McMillan A, Seymour E, Hirata J, de Guzman J, Sharma S, Jin HY, Musick L, Diefenbach C. Polatuzumab vedotin plus rituximab and lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma: a cohort of a multicentre, single-arm, phase 1b/2 study. Lancet Haematol. 2024 Jan 5:S2352-3026(23)00345-9. doi: 10.1016/S2352-3026(23)00345-9. Epub ahead of print. PMID: 38190832.

Urological Cancers

A total of 3 studies were located. These included a phase 2 trial that investigated tremelimumab in patients with metastatic urothelial cancer previously treated with PD-1/PD-L1 blockade and found an objective response rate of 8.3%, with two partial responses and stable disease in 20.8% of patients (1); a phase 1 dose-escalation study that investigated AGS15E monotherapy in patients with metastatic urothelial carcinoma, resulting in an objective response rate of 18.3% overall and 27.3% in the CPI-exposed subgroup (2); and a phase 1 trial of stereotactic body radiotherapy (SBRT) using the SIB-VMAT technique in patients with low- and intermediate-risk prostate cancer, demonstrating feasibility and safety with no severe acute toxicities and maximum tolerated dose identified as 50 Gy in five fractions (3).

References

  1. Miller EJ, Rose TL, Maughan BL, Milowsky MI, Bilen MA, Carthon BC, Gao X, Rapisuwon S, Zhao Q, Yu M, Agarwal N, Galsky MD. Phase 2 trial of tremelimumab in patients with metastatic urothelial cancer previously treated with programmed death 1/programmed death ligand 1 blockade. Cancer. 2024 Jan 5. doi: 10.1002/cncr.35179. Epub ahead of print. PMID: 38180804.

  2. Petrylak DP, Eigl BJ, George S, Heath EI, Hotte SJ, Chism DD, Nabell LM, Picus J, Cheng SY, Appleman LJ, Sonpavde GP, Morgans AK, Pourhosseini P, Wu R, Standley L, Croitoru R, Yu EY. Phase I Dose-Escalation Study of the Safety and Pharmacokinetics of AGS15E Monotherapy in Patients with Metastatic Urothelial Carcinoma. Clin Cancer Res. 2024 Jan 5;30(1):63-73. doi: 10.1158/1078-0432.CCR-22-3627. PMID: 37861407; PMCID: PMC10767306.

  3. Deodato F, Ferro M, Bonome P, Pezzulla D, Romano C, Buwenge M, Cilla S, Morganti AG, Macchia G. Stereotactic body radiotherapy (SIB-VMAT technique) to dominant intraprostatic lesion (DIL) for localized prostate cancer: a dose-escalation trial (DESTROY-4). Strahlenther Onkol. 2024 Jan 5. doi: 10.1007/s00066-023-02189-0. Epub ahead of print. PMID: 38180492.

Gynecological Cancers

A total of 5 studies were located. These included a phase II trial that investigated carboplatin, nab-paclitaxel, and pembrolizumab in metastatic triple-negative breast cancer and found an overall response rate of 48.0% (1), a phase II trial that investigated pegylated liposomal doxorubicin, cyclophosphamide, trastuzumab/pertuzumab, and nab-paclitaxel in HER2-positive breast cancer with a pathological complete response rate of 80.2% (2), a phase II trial that evaluated abemaciclib combined with trastuzumab, with or without fulvestrant, in HR+, HER2+ metastatic breast cancer showing a median overall survival of 31.1 months in one arm (3), a phase II trial that examined a combination of ipilimumab and nivolumab in refractory gestational trophoblastic neoplasia with an overall response rate of 75% (4), and a phase II trial that tested olaparib plus durvalumab, with or without bevacizumab, in PARP inhibitor-naïve platinum-sensitive relapsed ovarian cancer, showing an objective response rate of 92.2% in one cohort (5).

References

  1. Wilkerson AD, Parthasarathy PB, Stabellini N, Mitchell C, Pavicic PG Jr, Fu P, Rupani A, Husic H, Rayman PA, Swaidani S, Abraham J, Budd GT, Moore H, Al-Hilli Z, Ko JS, Baar J, Chan TA, Alban T, Diaz-Montero CM, Montero AJ. Phase II Clinical Trial of Pembrolizumab and Chemotherapy Reveals Distinct Transcriptomic Profiles by Radiologic Response in Metastatic Triple-Negative Breast Cancer. Clin Cancer Res. 2024 Jan 5;30(1):82-93. doi: 10.1158/1078-0432.CCR-23-1349. PMID: 37882661; PMCID: PMC10767305.

  2. Yang JX, Yang YQ, Hu WY, Yang L, Wu J, Wen XX, Yu J, Huang ML, Xu DD, Tie DC, Wang L, Li FF, Li NL. A Phase II Study of Neoadjuvant PLD/Cyclophosphamide and Sequential nab-Paclitaxel Plus Dual HER2 Blockade in HER2-Positive Breast Cancer. Oncologist. 2024 Jan 5;29(1):e15-e24. doi: 10.1093/oncolo/oyad160. PMID: 37279780; PMCID: PMC10769796.

  3. Tolaney SM, Goel S, Nadal J, Denys H, Borrego MR, Litchfield LM, Liu J, Appiah AK, Chen Y, André F. Overall Survival and Exploratory Biomarker Analyses of Abemaciclib plus Trastuzumab with or without Fulvestrant versus Trastuzumab plus Chemotherapy in HR+, HER2+ Metastatic Breast Cancer Patients. Clin Cancer Res. 2024 Jan 5;30(1):39-49. doi: 10.1158/1078-0432.CCR-23-1209. PMID: 37906649; PMCID: PMC10767303.

  4. Patel SP, Othus M, Chae YK, Dennis MJ, Gordon S, Mutch D, Samlowski W, Robinson WRR, Sharon E, Ryan C, Lopez G, Plets M, Blanke C, Kurzrock R. A Phase II Basket Trial of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART SWOG 1609 Cohort 47) in Patients with Gestational Trophoblastic Neoplasia. Clin Cancer Res. 2024 Jan 5;30(1):33-38. doi: 10.1158/1078-0432.CCR-23-2293. PMID: 37882676.

  5. Drew Y, Kim JW, Penson RT, O'Malley DM, Parkinson C, Roxburgh P, Plummer R, Im SA, Imbimbo M, Ferguson M, Rosengarten O, Steeghs N, Kim MH, Gal-Yam E, Tsoref D, Kim JH, You B, De Jonge M, Lalisang R, Gort E, Bastian S, Meyer K, Feeney L, Baker N, Ah-See ML, Domchek SM, Banerjee S; MEDIOLA Investigators. Olaparib plus Durvalumab, with or without Bevacizumab, as Treatment in PARP Inhibitor-Naïve Platinum-Sensitive Relapsed Ovarian Cancer: A Phase II Multi-Cohort Study. Clin Cancer Res. 2024 Jan 5;30(1):50-62. doi: 10.1158/1078-0432.CCR-23-2249. PMID: 37939124; PMCID: PMC10767301.

Cancers of Unknown Prime Origin

One study was located; a phase I trial that investigated LY3405105, a covalent inhibitor of cyclin-dependent kinase 7, in patients with advanced solid tumors and found limited clinical activity with common toxicities such as gastrointestinal events, myelosuppression, fatigue, and asthenia (1). No plans for further development of this drug regimen were indicated.

Reference

  1. Garralda E, Schram AM, Bedard PL, Schwartz GK, Yuen E, McNeely SC, Ribeiro S, Cunningham J, Wang Y, Urunuela A, Xu X, LoRusso P. A Phase I Dose-Escalation Study of LY3405105, a Covalent Inhibitor of Cyclin-Dependent Kinase 7, Administered to Patients With Advanced Solid Tumors. Oncologist. 2024 Jan 5;29(1):e131-e140. doi: 10.1093/oncolo/oyad215. PMID: 37531083; PMCID: PMC10769797.

Thoracic Cancers

A total of 2 studies were located. These included a phase 2 trial that investigated E7389-LF in combination with nivolumab in patients with small cell lung cancer (SCLC) and found an objective response rate of 24.2% with a median progression-free survival of 3.98 months (1), and a phase I/II trial that investigated carboplatin, nab-paclitaxel, and pembrolizumab in patients with advanced non-small cell lung cancer (NSCLC) and found an overall response rate of 35%, with a median progression-free survival of 5.6 months and a median overall survival of 15.4 months (2).

References

  1. Nishio M, Murakami S, Kawakami H, Okishio K, Tamiya M, Kobayashi H, Fujimoto D, Sugawara S, Kozuki T, Oya Y, Izumi H, Shiroyama T, Satouchi M, Yamamoto N, Kaname S, Matsuoka D, Otake Y, Takase T, Semba T, Azuma K. Phase 2 Study of the Liposomal Formulation of Eribulin (E7389-LF) in Combination with Nivolumab: Results from the Small Cell Lung Cancer Cohort. Cancer Res Commun. 2024 Jan 5. doi: 10.1158/2767-9764.CRC-23-0313. Epub ahead of print. PMID: 38181055.

  2. Gentzler RD, Mohindra NA, Jalal SI, Reckamp KL, Hall RD, Hanna NH, Chae YK, Koczywas M, Helenowski IB, Patel JD. Phase I/II Trial of Carboplatin, Nab-paclitaxel, and Pembrolizumab for Advanced Non-Small Cell Lung Cancer: Hoosier Cancer Research Network LUN13-175. Oncologist. 2024 Jan 5;29(1):47-56. doi: 10.1093/oncolo/oyad180. PMID: 37390616; PMCID: PMC10769801.

Gastrointestinal Cancers

A total of 3 studies were located. These included a phase III trial that investigated fluorouracil, leucovorin, and irinotecan plus cetuximab versus cetuximab alone as maintenance therapy in first-line therapy for RAS/BRAF wild-type metastatic colorectal cancer (mCRC) and found that cetuximab alone did not establish noninferiority to continuous FOLFIRI/Cet therapy in terms of progression-free survival (1); a randomized clinical trial that investigated primary surgery followed by selective chemoradiotherapy versus preoperative chemoradiotherapy followed by surgery for locally advanced rectal cancer (LARC) and found that the primary surgery approach was inferior to preoperative CRT in disease-free survival rates (2); and a phase II trial that investigated preoperative chemotherapy with docetaxel, oxaliplatin, and S-1 for gastric cancer with extensive lymph node metastasis (ELM) and found favorable pathological responses with an acceptable toxicity profile, suggesting its potential as a promising treatment approach (3).

References

  1. Pinto C, Orlandi A, Normanno N, Maiello E, Calegari MA, Antonuzzo L, Bordonaro R, Zampino MG, Pini S, Bergamo F, Tonini G, Avallone A, Latiano TP, Rosati G, Cogoni AA, Ballestrero A, Zaniboni A, Roselli M, Tamberi S, Barone C. Fluorouracil, Leucovorin, and Irinotecan Plus Cetuximab Versus Cetuximab as Maintenance Therapy in First-Line Therapy for RAS and BRAF Wild-Type Metastatic Colorectal Cancer: Phase III ERMES Study. J Clin Oncol. 2024 Jan 5:JCO2301021. doi: 10.1200/JCO.23.01021. Epub ahead of print. PMID: 38181312.

  2. Li J, Hu YT, Liu CC, Wang LH, Ju HX, Huang XF, Chi P, Du JL, Wang JP, Xiao Y, Lin GL, Zhang W, Zhao H, Liu M, Song YM, Xu D, Wang JW, Sun LF, Xie HT, Cao HF, Xiao Q, Wang J, Wu QB, Li DC, Dai S, Jiang WZ, Shen L, Yuan Y, Wang ZQ, Ding KF. Primary surgery followed by selective chemoradiotherapy versus preoperative chemoradiotherapy followed by surgery for locally advanced rectal cancer: A Randomized Clinical Trial. Int J Radiat Oncol Biol Phys. 2024 Jan 5:S0360-3016(23)08261-5. doi: 10.1016/j.ijrobp.2023.12.027. Epub ahead of print. PMID: 38185388.

  3. Kurokawa Y, Doki Y, Kitabayashi R, Yoshikawa T, Nomura T, Tsuji K, Goto M, Cho H, Hihara J, Hiki N, Nunobe S, Mizusawa J, Boku N, Terashima M. Short-term outcomes of preoperative chemotherapy with docetaxel, oxaliplatin, and S-1 for gastric cancer with extensive lymph node metastasis (JCOG1704). Gastric Cancer. 2024 Jan 5. doi: 10.1007/s10120-023-01453-7. Epub ahead of print. PMID: 38180622.

Central Nervous System Cancers

One study was located; a phase III trial that investigated metabolic imaging-guided dose escalation of radio-chemotherapy in patients with newly diagnosed glioblastoma (GBM) and found no significant improvement in overall survival among these patients (1). The study, known as the SPECTRO GLIO trial, involved 180 patients who were randomly assigned to receive either a standard dose or a high dose of radiotherapy. The results showed median overall survival of 22.6 months in the high dose group and 22.2 months in the standard dose group, with no increase in toxicity rates. However, for patients with MGMT methylated tumors, the high dose group showed longer median overall survival.

Reference

  1. Laprie A, Noel G, Chaltiel L, Truc G, Sunyach MP, Charissoux M, Magne N, Auberdiac P, Biau J, Ken S, Tensaouti F, Khalifa J, Sidibe I, Roux FE, Vieillevigne L, Catalaa I, Boetto S, Uro-Coste E, Supiot S, Bernier V, Filleron T, Mounier M, Poublanc M, Olivier P, Delord JP, Cohen-Jonathan-Moyal E. Randomized phase III trial of metabolic imaging-guided dose escalation of radio-chemotherapy in patients with newly diagnosed glioblastoma (SPECTRO GLIO trial). Neuro Oncol. 2024 Jan 5;26(1):153-163. doi: 10.1093/neuonc/noad119. PMID: 37417948; PMCID: PMC10768994.

Rare Cancers

One study was located; a phase I/II trial that investigated combined RAF and MEK inhibition in patients with advanced cancer characterized by activating non-V600 BRAF alterations and found that the treatment was well-tolerated but did not sufficiently inhibit activated non-V600 BRAF-mutant tumors in patients (1). The study involved 15 patients with various cancer types, including gastrointestinal, genitourinary, melanoma, and lung cancers. The main outcomes were that one patient had a confirmed partial response, eight experienced stable disease, and six had radiographic or clinical progression.

Reference

  1. Rustgi N, Maria A, Toumbacaris N, Zhao H, Kargus K, Bryant M, Waksmundzki A, Aricescu I, Lefkowitz RA, Li BT, Chou J, Capanu M, de Stanchina E, Misale S, Shia J, Yaeger R. Combined RAF and MEK Inhibition to Treat Activated Non-V600 BRAF-Altered Advanced Cancers. Oncologist. 2024 Jan 5;29(1):15-24. doi: 10.1093/oncolo/oyad247. PMID: 37616543; PMCID: PMC10769795.

Skin Cancers

A total of 1 study was located. This included a phase II trial that investigated the combination of Sotigalimab and Nivolumab in subjects with metastatic melanoma with confirmed disease progression on anti-PD-1 therapy and found an objective response rate (ORR) of 15% (1). The study highlighted that five subjects achieved a partial response, with the median duration of response being at least 26 months. Furthermore, two patients had stable disease for more than six months. While adverse events were reported in 89% of patients, the combination treatment exhibited a favorable safety profile with no serious adverse events, deaths, or discontinuations due to adverse events. The results suggest the potential of this combination in patients resistant to anti-PD-1 therapy, warranting further investigation.

Reference

Weiss SA, Sznol M, Shaheen M, Berciano-Guerrero MÁ, Couselo EM, Rodríguez-Abreu D, Boni V, Schuchter LM, Gonzalez-Cao M, Arance A, Wei W, Ganti AK, Hauke RJ, Berrocal A, Iannotti NO, Hsu FJ, Kluger HM. A Phase II Trial of the CD40 Agonistic Antibody Sotigalimab (APX005M) in Combination with Nivolumab in Subjects with Metastatic Melanoma with Confirmed Disease Progression on Anti-PD-1 Therapy. Clin Cancer Res. 2024 Jan 5;30(1):74-81. doi: 10.1158/1078-0432.CCR-23-0475. PMID: 37535056; PMCID: PMC10767304.