Oncology Daily Report: 01/29/2024

Phase 3 Studies

Prostate Cancer

A phase 3 randomized, controlled study investigated the effect of PSMA-PET/computed tomography (CT) scan prior to salvage radiotherapy (SRT) planning in 193 patients with biochemical recurrence of prostate cancer after radical prostatectomy and found that PSMA-PET findings led to major management changes in SRT planning in 33/102 (32.4%) patients in the investigational arm compared to the control arm (1). The study demonstrated a 23% difference in the frequency of major changes between the control (22% [17/76]) and the PSMA-PET intervention arm (45% [46/102]), with a significant impact on treatment strategies, including a 17.6% difference in treatment escalation frequency between the control arm (12%) and the intervention arm (29%).

Reference

Wong LM, Sutherland T, Perry E, Tran V, Spelman T, Corcoran N, Lawrentschuk N, Woo H, Lenaghan D, Buchan N, Bax K, Symons J, Saeed Goolam A, Chalasani V, Hegarty J, Thomas L, Christov A, Ng M, Khanani H, Lee SF, Taubman K, Tarlinton L. Fluorine-18-labelled Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography or Magnetic Resonance Imaging to Diagnose and Localise Prostate Cancer. A Prospective Single-arm Paired Comparison (PEDAL). Eur Urol Oncol. 2024 Jan 27:S2588-9311(24)00026-9. doi: 10.1016/j.euo.2024.01.002. Epub ahead of print. PMID: 38281891.

Phase 2 Studies

Diffuse Large B-cell CNS Lymphoma (Primary)

A phase 2 single-arm study investigated the effect of high-dose chemotherapy and autologous haematopoietic stem-cell transplantation in 51 patients with primary diffuse large B-cell CNS lymphoma in Germany (1). The study, known as MARTA, was conducted at 15 research hospitals and found that at a median follow-up of 23.0 months, 23 (45%) of patients progressed, relapsed, or died, with a 12-month progression-free survival of 58.8%. The most common grade 3-5 toxicities were thrombocytopenia and leukopenia during induction treatment, and leukopenia during high-dose chemotherapy and autologous HSCT. There were three treatment-related deaths (6%) due to infectious complications.

Reference

Schorb E, Isbell LK, Kerkhoff A, Mathas S, Braulke F, Egerer G, Röth A, Schliffke S, Borchmann P, Brunnberg U, Kroschinsky F, Möhle R, Rank A, Wellnitz D, Kasenda B, Pospiech L, Wendler J, Scherer F, Deckert M, Henkes E, von Gottberg P, Gmehlin D, Backenstraß M, Jensch A, Burger-Martin E, Grishina O, Fricker H, Malenica N, Orbán A, Duyster J, Ihorst G, Finke J, Illerhaus G. High-dose chemotherapy and autologous haematopoietic stem-cell transplantation in older, fit patients with primary diffuse large B-cell CNS lymphoma (MARTA): a single-arm, phase 2 trial. Lancet Haematol. 2024 Jan 29:S2352-3026(23)00371-X. doi: 10.1016/S2352-3026(23)00371-X. Epub ahead of print. PMID: 38301670.

Non-Small Cell Lung Cancer (Advanced)

A multi-cohort, phase II study investigated the safety and efficacy of QL1706 (anti-PD-1 IgG4/CTLA-4 antibody) plus chemotherapy with or without bevacizumab in 91 patients with advanced non-small cell lung cancer, showing an objective response rate of 45% in patients with wild-type EGFR and 54.8% in patients with mutated EGFR (1). Patients with wild-type EGFR had a median progression-free survival of 6.8 months, while those with mutated EGFR had 8.5 months. The study reported treatment-related adverse events, including decreased appetite and anemia, with 33.0% of patients experiencing grade ≥3 adverse events.

Reference

Huang Y, Yang Y, Zhao Y, Zhao H, Zhou N, Zhang Y, Chen L, Zhou T, Chen G, Wu T, Lu L, Xue S, Kang X, Zhang L, Fang W. QL1706 (anti-PD-1 IgG4/CTLA-4 antibody) plus chemotherapy with or without bevacizumab in advanced non-small cell lung cancer: a multi-cohort, phase II study. Signal Transduct Target Ther. 2024 Jan 29;9(1):23. doi: 10.1038/s41392-023-01731-x. PMID: 38282003; PMCID: PMC10822847.

Small Cell Lung Cancer

A phase II study investigated the effect of the liposomal formulation of eribulin (E7389-LF) in combination with nivolumab in 34 patients with unresectable/measurable small cell lung cancer (SCLC) and disease progression after first-line platinum-based chemotherapy with/without an immune checkpoint inhibitor (ICI) and found an objective response rate (ORR) of 24.2% with a median progression-free survival (PFS) of 3.98 months (1). Treatment-related, treatment-emergent adverse events occurred in 97.1% (any grade) and 82.4% (grade ≥3) of enrolled patients, with neutropenia being the most common event.

Reference

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 II 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 29;4(1):226-235. doi: 10.1158/2767-9764.CRC-23-0313. PMID: 38181055; PMCID: PMC10823908.

Phase 1/2 Studies

Non-Small-Cell Lung Cancer (Advanced ALK-Positive)

A multicenter, open-label, single-arm, phase I/II study investigated the effect of ficonalkib (SY-3505) in 127 patients with advanced ALK-positive non-small-cell lung cancer resistant to second-generation ALK tyrosine kinase inhibitors (1). The study determined 600 mg daily as the recommended phase II dose after a dose-escalation and dose-expansion phase. The objective response rate was 38.3% in phase I and 47.5% in phase II for patients receiving 600 mg daily, with an intracranial objective response rate of 37.5% in patients with measurable brain lesions at baseline. Treatment-related adverse events occurred in 85.5% of patients in phase I, with 19.4% experiencing ≥ grade 3 events, and 90.9% of patients in phase II, with 14.8% experiencing ≥ grade 3 events.

Reference

Shi Y, Hu X, Li X, Gong C, Wang K, Li Y, Zhang S, Luo Y, Wang P, Jiang L, Meng X, Dong X, Wang H, Yang R, Mei Q, Liu B, Yang L, Sun Y. Ficonalkib (SY-3505) in Advanced ALK-Positive Non-Small-Cell Lung Cancer: A Multicenter, Open-Label, Single-Arm, Phase I/Ⅱ Study. J Thorac Oncol. 2024 Jan 29:S1556-0864(24)00035-2. doi: 10.1016/j.jtho.2024.01.015. Epub ahead of print. PMID: 38295954.

Phase 1 Studies

Acute myeloid leukemia

Two phase 1b studies investigated the safety, pharmacokinetics, and efficacy of quizartinib in combination with standard induction and consolidation chemotherapy in 14 patients with newly diagnosed acute myeloid leukemia in Japan and China (1). No dose-limiting toxicities were observed at dose levels up to 40 mg/day. Grade 3 or higher quizartinib-related treatment-emergent adverse events included febrile neutropenia, hematologic toxicities, and infections. QT prolongation was observed in 5 patients. The studies confirmed the tolerability of the quizartinib dose and chemotherapy regimens used in the QuANTUM-First study.

Reference

Qi J, Choi I, Ota S, Ichikawa S, Fujishima N, Iida H, Sugiura I, Sugiura K, Murata Y, Inoue H, Ohwada S, Wang J. Safety and Pharmacokinetics of Quizartinib Combination Therapy With Standard Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia: Results from Two Phase 1 Trials in Japan and China. Clin Pharmacol Drug Dev. 2024 Jan 29. doi: 10.1002/cpdd.1353. Epub ahead of print. PMID: 38284515.

Castration-Resistant Prostate Cancer (Metastatic)

A phase I open label, repeated dose-escalation and expansion study investigated the effect of [(225)Ac]Ac-PSMA-I&T in up to 30 patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) after at least one line of chemotherapy and/or one line of nonsteroidal antiandrogen and found the trial aims to assess the safety and tolerability to recommend the optimal dose for the phase II trial (1). The trial was conducted as an investigator-initiated, single-center trial and registered under ClinicalTrials.gov (NCT05902247).

Reference

Ling SW, van der Veldt AAM, Konijnenberg M, Segbers M, Hooijman E, Bruchertseifer F, Morgenstern A, de Blois E, Brabander T. Evaluation of the tolerability and safety of [225Ac]Ac-PSMA-I&T in patients with metastatic prostate cancer: a phase I dose escalation study. BMC Cancer. 2024 Jan 29;24(1):146. doi: 10.1186/s12885-024-11900-y. PMID: 38287346; PMCID: PMC10826262.

Glioblastoma

A Phase I open-label study investigated the effect of r-(-)-gossypol (AT-101) in 16 patients with newly diagnosed glioblastoma and 56 patients with recurrent glioblastoma, finding that AT-101 can be safely administered with radiation therapy and TMZ in patients with newly diagnosed glioblastoma without unique toxicity to CNS tumors (1). Median survival times for newly diagnosed patients were 15.2 and 18.2 months for Arm I and Arm II, respectively. For recurrent glioblastoma, the median OS was 5.7 months, with 29% of patients achieving stable disease as best response.

Reference

Fiveash JB, Ye X, Peerboom DM, Mikkelsen T, Chowdhary S, Rosenfeld M, Lesser GJ, Fisher J, Desideri S, Grossman S, Leopold L, Nabors LB. Clinical trials of R-(-)-gossypol (AT-101) in newly diagnosed and recurrent glioblastoma: NABTT 0602 and NABTT 0702. PLoS One. 2024 Jan 29;19(1):e0291128. doi: 10.1371/journal.pone.0291128. PMID: 38285688; PMCID: PMC10824421.

Solid Tumors (Advanced)

A phase I open-label, multicenter, first-in-human study investigated the effect of gartisertib, an oral inhibitor of ataxia telangiectasia and Rad3-related protein (ATR), ± carboplatin in 97 patients with advanced solid tumours and found that gartisertib was generally well-tolerated at lower doses; however, unexpected liver toxicity prevented further dose escalation (1). The recommended phase II dose (RP2D) for gartisertib was determined as 250 mg once daily in cohort A2. Despite general tolerability, the development of gartisertib was discontinued due to liver toxicity issues.

Reference

Burris HA, Berlin J, Arkenau T, Cote GM, Lolkema MP, Ferrer-Playan J, Kalapur A, Bolleddula J, Locatelli G, Goddemeier T, Gounaris I, de Bono J. A phase I study of ATR inhibitor gartisertib (M4344) as a single agent and in combination with carboplatin in patients with advanced solid tumours. Br J Cancer. 2024 Jan 29. doi: 10.1038/s41416-023-02436-2. Epub ahead of print. PMID: 38287179.