Oncology Daily Report: 01/22/2024
Phase 3 Studies
Non-Small-Cell Lung Cancer (Metastatic)
The phase III CheckMate 722 trial (ClinicalTrials.gov identifier: NCT02864251) investigated the effect of nivolumab plus chemotherapy versus chemotherapy alone in 294 patients with epidermal growth factor receptor (EGFR)-mutated metastatic non-small-cell lung cancer (NSCLC) after disease progression on EGFR tyrosine kinase inhibitors and found no significant improvement in progression-free survival (PFS) (median, 5.6 v 5.4 months; HR, 0.75 [95% CI, 0.56 to 1.00]) (1). Median overall survival (OS) was 19.4 months with nivolumab plus chemotherapy versus 15.9 months with chemotherapy, while objective response rate (ORR) was 31.3% versus 26.7%, and median duration of response (DOR) was 6.7 versus 5.6 months, respectively. Grade 3/4 treatment-related adverse events occurred in 44.7% with nivolumab plus chemotherapy and 29.4% with chemotherapy alone.
Reference
Mok T, Nakagawa K, Park K, Ohe Y, Girard N, Kim HR, Wu YL, Gainor J, Lee SH, Chiu CH, Kim SW, Yang CT, Wu CL, Wu L, Lin MC, Samol J, Ichikado K, Wang M, Zhang X, Sylvester J, Li S, Forslund A, Yang JC. Nivolumab Plus Chemotherapy in Epidermal Growth Factor Receptor-Mutated Metastatic Non-Small-Cell Lung Cancer After Disease Progression on Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: Final Results of CheckMate 722. J Clin Oncol. 2024 Jan 22:JCO2301017. doi: 10.1200/JCO.23.01017. Epub ahead of print. PMID: 38252907.
Phase 2 Studies
Acute Myeloid Leukemia
A phase 2 open-label study investigated the effect of epigenetic priming with decitabine followed by cytarabine in 44 patients with previously untreated acute myeloid leukemia (AML) in older patients and found a complete remission (CR/CRi) rate of 59% of all patients, 66.7% of evaluable patients, with 4- and 8-week mortality rates of 2.3% and 9.1%, respectively, and a median overall survival (OS) of 10.7 months (1). This trial was registered at www.clinicaltrials.gov as # NCT01829503.
Reference
Im A, Quann K, Agha M, Raptis A, Redner RL, Hou JZ, Farah R, Dorritie KA, Sehgal AR, Normolle D, Bovbjerg DH, Aggarwal N, Herman J, Lontos K, Boyiadzis M. Phase 2 study of epigenetic priming with decitabine followed by cytarabine for acute myeloid leukemia in older patients. Am J Hematol. 2024 Jan 22. doi: 10.1002/ajh.27212. Epub ahead of print. PMID: 38258329.
Castration-Resistant Prostate Cancer (mCRPC) (Metastatic)
A phase II multicenter study investigated the effect of enzalutamide in 68 patients with mCRPC and measurable metastases, including visceral and/or extra-regional lymph nodes (1). The study found that at the 3-month assessment, 24 patients presented stable disease (SD), 1 patient achieved a complete response (CR), and 23 patients had a partial response (PR), resulting in a 3-month disease control rate (DCR) of 72%. Discontinuations due to adverse events (AEs), disease-related death, or disease progression occurred in 9%, 6%, and 48% of patients, respectively. The most common AEs were fatigue (49%) and hypertension (33%). Basal detection of ARv7 was significantly associated with poor treatment response. The study concluded that enzalutamide is effective in men with mCRPC and measurable metastatic lesions in visceral and/or lymph node sites. Trial Registration: ClinicalTrials.gov Identifier: NCT03103724.
References
Sepe P, Procopio G, Pircher CC, Basso U, Caffo O, Cappelletti V, Claps M, De Giorgi U, Fratino L, Guadalupi V, Miodini P, De Marco C, Perrucci B, Mennitto A, Santini D, Spina F, Stellato M, de Braud F, Verzoni E. A phase II study evaluating the efficacy of enzalutamide and the role of liquid biopsy for evaluation of ARv7 in mCRPC patients with measurable metastases including visceral disease (Excalibur study). Ther Adv Med Oncol. 2024 Jan 22;16:17588359231217958. doi: 10.1177/17588359231217958. PMID: 38264520; PMCID: PMC10804904.
Endometrial Carcinoma and Carcinosarcoma (Advanced)
A phase 2 open-label study investigated the effect of zanidatamab in 16 patients with HER2-overexpressed metastatic endometrial carcinoma and carcinosarcoma who received prior treatment and found an overall response rate (ORR) of 6.2% (1). The study did not meet its primary efficacy endpoint, with a clinical benefit rate of 37.5% observed by 24 weeks. CLINICALTRIALS.gov identifier: NCT04513665.
Reference
Lumish M, Chui MH, Zhou Q, Iasonos A, Sarasohn D, Cohen S, Friedman C, Grisham R, Konner J, Kyi C, Rubinstein M, Troso-Sandoval T, Aghajanian C, Makker V. A phase 2 trial of zanidatamab in HER2-overexpressed advanced endometrial carcinoma and carcinosarcoma (ZW25-IST-2). Gynecol Oncol. 2024 Jan 22;182:75-81. doi: 10.1016/j.ygyno.2023.12.028. Epub ahead of print. PMID: 38262242.
Non-Small Cell Lung Cancer (NSCLC)
A phase 2 study compared nivolumab combined with docetaxel versus nivolumab monotherapy in 22 patients with previously treated advanced NSCLC (1). The study observed a significantly longer median progression-free survival (PFS) in the nivolumab plus docetaxel group (4.0 months) compared to the nivolumab group (2.0 months). The objective response rate was 10.0% in the nivolumab group and 25% in the nivolumab + docetaxel group. Disease control was higher in the nivolumab plus docetaxel arm (40.0% versus 83.3%). An improvement in overall survival (OS) was noted in the nivolumab + docetaxel arm but was not statistically significant (10.0 months versus 7.2 months). The study suggests that adding docetaxel to nivolumab may benefit NSCLC patients progressing on platinum-based chemotherapy.
Reference
Wang Y, Hao Q, Nie J, Dai L, Hu W, Zhang J, Chen X, Ma X, Tian G, Han J, Han S, Wu D, Long J, Zhang Z, Fang J. Nivolumab combined docetaxel versus nivolumab in patients with previously treated nonsmall cell lung cancer: a phase 2 study. Anticancer Drugs. 2024 Jan 22. doi: 10.1097/CAD.0000000000001569. Epub ahead of print. PMID: 38240789.
Phase 1 Studies
Cutaneous Squamous Cell Carcinoma
A Phase I study investigated the effect of cemiplimab in 12 kidney transplant recipients with advanced cutaneous squamous cell carcinoma. Patients received cemiplimab 350 mg intravenously once every 3 weeks for up to 2 years and were assessed for response every 8 weeks (1). No kidney rejection or loss was observed. A response to cemiplimab was observed in five of 11 evaluable patients (46%), including two with durable responses beyond a year. Treatment-related grade 3 or greater adverse events occurred in five patients (42%). This study was funded by Regeneron Pharmaceuticals and its ClinicalTrials.gov identifier is NCT04339062.
Reference
Hanna GJ, Dharanesswaran H, Giobbie-Hurder A, Harran JJ, Liao Z, Pai L, Tchekmedyian V, Ruiz ES, Waldman AH, Schmults CD, Riella LV, Lizotte P, Paweletz CP, Chandraker AK, Murakami N, Silk AW. Cemiplimab for Kidney Transplant Recipients With Advanced Cutaneous Squamous Cell Carcinoma. J Clin Oncol. 2024 Jan 22:JCO2301498. doi: 10.1200/JCO.23.01498. Epub ahead of print. PMID: 38252908.
Recurrent Ovarian, Primary Peritoneal, Fallopian Tube, Endometrial Cancer, or Triple Negative Breast Cancer
A Phase I study investigated the effect of mirvetuximab soravtansine and gemcitabine in 20 patients with FRα-positive recurrent ovarian, primary peritoneal, fallopian tube, endometrial cancer, or triple negative breast cancer (1). The MTD/RP2D was MIRV 6 mg/kg AIBW D1 and gemcitabine 800 mg/m2 IV, D1 and D8, every 21 days. At this dose, 5/7 patients demonstrated a partial response (PR), including 2 confirmed ovarian responses whose time-to-progression and duration of response were 7.9/5.4 and 8.0/5.7 months respectively. Nine of 20 patients (45%) achieved PR as their best response, with 3/20 patients or 15% confirmed PR.
Reference
Cristea MC, Stewart D, Synold T, Ruel N, Mortimer J, Wang E, Jung A, Wilczynski S, Konecny GE, Eng M, Kilpatrick L, Han E, Dellinger T, Hakim A, Lee S, Morgan RJ, Wakabayashi MT, Frankel PH. A phase I study of Mirvetuximab Soravtansine and gemcitabine in patients with FRα-positive recurrent ovarian, primary peritoneal, fallopian tube, or endometrial cancer, or triple negative breast cancer. Gynecol Oncol. 2024 Jan 22;182:124-131. doi: 10.1016/j.ygyno.2023.12.017. Epub ahead of print. PMID: 38262235.