Programmed death (ligand) 1 (PD-[L]1) inhibitor-based regimens are the standard of care in first-line metastatic non-small cell lung cancer (mNSCLC) and novel combinations are needed to further improve outcomes. Sacituzumab govitecan (SG), a Trop-2-directed antibody-drug conjugate, demonstrated clinical activity and manageable safety in pretreated patients with mNSCLC. The ongoing, global, open-label, multicohort, Phase 2 EVOKE-02 study (NCT05186974) is evaluating SG + pembrolizumab (pembro) ± platinum agent as first-line treatment for mNSCLC.

8039 Background: MagnetisMM-3 (NCT04649359) is an open-label, multicenter, registrational phase 2 study evaluating the efficacy and safety of elranatamab monotherapy in pts with RRMM; pts naïve to BCMA-directed therapies were enrolled in Cohort A. Methods: Eligible pts were refractory to at least 1 PI, 1 IMiD, and 1 anti-CD38 antibody. Pts received SC elranatamab in 28-d cycles with step-up doses of 12 mg on C1D1 and 32 mg on C1D4 followed by 76 mg QW beginning C1D8. Pts treated for 6 cycles and achieving partial response (PR) or better with response persisting ≥2 mo were switched to 76 mg Q2W, 46 and 58 pts are included in the Q2W efficacy and safety analyses, respectively. Results: Overall, 123 pts received elranatamab. Median pt age was 68.0 y (range, 36−89), 63.4% of pts had an ECOG PS ≥1 and median prior lines of therapy was 5.0 (2−22); 96.7% and 42.3% of pts were triple-class- and penta-drug refractory, respectively. At data cutoff (~12 mo after last pt initial dose), the median follow up was 12.8 mo (0.2−22.7); 34.1% of pts remained on treatment. Most common reasons for permanent treatment discontinuation were progressive disease (39.0%) and adverse events (AE; 13.8%). Objective response rate per blinded independent central review (BICR) was 61% (95% CI 51.8−69.6), with 39 (31.7%) pts with complete response (CR) or stringent CR (sCR); very good partial response (VGPR) and PR were achieved in 29 (23.6%) and 7 (5.7%) pts, respectively. MRD-negativity (threshold 10–5) was achieved by 92.0% (n = 23/25) of evaluable pts. Median duration of response (mDOR) has not been reached (95% CI 12.9−NE) and DOR at 12 mo was 74.1% (95% CI 60.5−83.6). In pts with CR/sCR or VGPR, mDOR was not reached by 12 mo; in pts with PR, mDOR was 5.2 mo (95% CI 1.6−NE). There were 46 responders by BICR who switched to Q2W dosing ≥24 wk prior to the data cut-off; among these pts, 80.4% maintained/improved their response ≥24 wk after the switch. Median progression-free and overall survival have not been reached by 12 mo, and the respective rates (95% CI) at 12 mo were 57.1% (47.2−65.9) and 62.0% (52.8−70.0). Most common Grade 3/4 treatment emergent AEs were hematologic; Grade 3/4 non-hematologic events reported in ≥5% of pts were COVID-pneumonia (10.6%), hypokalemia (9.8%), pneumonia (7.3%), sepsis (6.5%), hypertension (6.5%), ALT increased (5.7%), and SARS-COV-2 test positive (5.7%). Among pts who switched to Q2W dosing, the incidence of Grade 3/4 AEs decreased by > 10% after the switch. Conclusions: Elranatamab remains efficacious and well tolerated in pts with RRMM after > 1 y of follow-up. Updated analysis with a median follow up of ~15 mo, the longest of all phase 2 BCMA-CD3 bispecific antibody studies, including the outcome of pts who switched to the Q2W dosing, will be presented. These results support continued elranatamab development for pts with MM. Clinical trial information: NCT04649359 .

TPS8601 Background: Taletrectinib (AB-106/DS-6051b) is a next-generation, brain-penetrant, ROS1/ NTRK tyrosine kinase inhibitor (TKI) and has shown clinically meaningful effect and safety profile in ROS1+ Non-Small Cell Lung Cancer (NSCLC) patients in phase 1 studies (Fujiwara et al, Oncotarget 2018; 9(34): 23729-23737; Ou et al, JTO Clin Res Rep. 2020 Oct 21;2(1):100108). Taletrectinib has also demonstrated activity against ROS1 G2032R resistance mutation and CNS metastases in the ongoing phase 2 TRUST study (NCT04395677) in China. Also, taletrectinib has shown preliminary efficacy against NTRK positive solid tumors in an ongoing phase 2 study (NCT04617054). Methods: TRUST-II study (NCT04919811) is a phase 2, global, multicenter, open-label, single-arm multi-cohort study evaluating the efficacy and safety of taletrectinib for ROS1 fusion-positive advanced metastatic NSCLC and other solid tumors. Taletrectinib will be given at 600 mg once daily in 21-day cycle. The patients with ROS1 fusions detected by local tests are eligible to enroll with retrospective confirmation by a central laboratory. The study consists of four cohorts: cohort 1: systemic chemotherapy naïve or ≤ one prior line and ROS1 TKI naïve NSCLC (N = 53); cohort 2: previously treated with one ROS1 TKI (crizotinib or entrectinib) and with progression who are either chemotherapy naïve or ≤ one line of platinum and/or pemetrexed based therapy for NSCLC (N = 46); cohort 3: ≤ 2 prior ROS1 TKIs and with progression who are either chemotherapy naïve or ≤ 2 lines of platinum and/or pemetrexed based therapy for NSCLC (N = 10); and cohort 4: systemic chemotherapy naïve or ≤ 2 prior lines of chemotherapy, but ROS1-TKI naïve ROS1 positive solid tumor other than NSCLC (N = 10). The primary endpoint is objective response rate (ORR) (RECIST v1.1) by independent review committee (IRC) assessment for cohorts 1 and 2. Key secondary endpoints include IRC-assessed duration of response, IRC-assessed intra-cranial ORR, progression free survival (PFS), overall survival (OS), and safety. This study is currently recruiting in Japan, Republic of Korea, and USA. Additional accrual is planned in Canada, China, and European Union. Clinical trial information: NCT04919811.

Taletrectinib (AB-106/DS-6051b) is a next-generation, brain-penetrant, ROS1/ NTRK tyrosine kinase inhibitor (TKI) and has shown clinically meaningful effect and safety profile in ROS1+ Non-Small Cell Lung Cancer (NSCLC) patients in phase 1 studies (Fujiwara et al, Oncotarget 2018; 9(34): 23729-23737; Ou et al, JTO Clin Res Rep. 2020 Oct 21;2(1):100108). Taletrectinib has also demonstrated activity against ROS1 G2032R resistance mutation and CNS metastases in the ongoing phase 2 TRUST study (NCT04395677) in China. Also, taletrectinib has shown preliminary efficacy against NTRK-positive solid tumors in an ongoing phase 2 study (NCT04617054). TRUST-II study (NCT04919811) is a phase 2, global, multicenter, open-label, single-arm multi-cohort study evaluating the efficacy and safety of taletrectinib for ROS1 fusion-positive advanced metastatic NSCLC and other solid tumors. Taletrectinib will be given at 600 mg once daily in 21-day cycle. The patients with ROS1 fusions detected by local tests are eligible to enroll with retrospective confirmation by a central laboratory. The study consists of four cohorts: cohort 1: systemic chemotherapy naïve or ≤ one prior line and ROS1 TKI naïve NSCLC (N=53); cohort 2: previously treated with one ROS1 TKI (crizotinib or entrectinib) and with progression who are either chemotherapy naïve or ≤ one line of platinum and/or pemetrexed based therapy for NSCLC (N=46); cohort 3: ≤ 2 prior ROS1 TKIs and with progression who are either chemotherapy naïve or ≤ 2 lines of platinum and/or pemetrexed based therapy for NSCLC (N=10); and cohort 4: systemic chemotherapy naïve or ≤ 2 prior lines of chemotherapy, but ROS1-TKI naïve ROS1-positive solid tumor other than NSCLC ( N=10). The primary endpoint is objective response rate (ORR) (RECIST v1.1) by independent review committee (IRC) assessment for cohorts 1 and 2. Key secondary endpoints include IRC-assessed duration of response, IRC-assessed intra-cranial ORR, progression free survival (PFS), overall survival (OS), and safety. This study is currently recruiting in Japan, Republic of Korea, and USA. Additional accrual is planned in Canada, China, and European Union. NCT04919811. The authors. AnHeart Therapeutic Inc.

Taletrectinib (AB-106/DS-6051b) is a next-generation, brain-penetrant, ROS1/ NTRK tyrosine kinase inhibitor (TKI) and has shown clinically meaningful effect and safety profile in ROS1+ Non-Small Cell Lung Cancer (NSCLC) patients in phase 1 studies (Fujiwara et al, Oncotarget 2018; 9(34): 23729-23737; Ou et al, JTO Clin Res Rep. 2020 Oct 21;2(1):100108). Taletrectinib has also demonstrated activity against ROS1 G2032R resistance mutation and CNS metastases in the ongoing phase 2 TRUST study (NCT04395677) in China. Also, taletrectinib has shown preliminary efficacy against NTRK positive solid tumors in an ongoing phase 2 study (NCT04617054)

Trilaciclib, an intravenous (IV) kinase inhibitor that protects hematopoeitic stem and progenitor cells during chemotherapy exposure, is FDA approved to decrease the incidence of chemotherapy-induced myelosuppression in patients (pts) with extensive-stage small cell lung cancer based on data from three randomized, placebo-controlled phase II trials. In another randomized phase II trial in pts with triple-negative breast cancer, administering trilaciclib prior to chemotherapy had limited myeloprotective effects, but improved overall survival (OS).

TPS3115 Background: NKTR-214 is an investigational cytokine designed to target CD122 (IL-2Rβ) expressed on immune cells (CD8+ T cells and NK cells) in order to expand these tumor-killing cells. NKTR-214 monotherapy increases newly proliferative CD8+ T cells and NK cells in tumors and increases cell surface PD-1 and PD-L1 expression, demonstrating a potentially synergistic mechanism with anti-PD-1 therapy. NKTR-214 plus nivolumab resulted in rapid tumor responses in pts with metastatic melanoma (mM), non-small cell lung cancer (mNSCLC), and renal cell carcinoma. Given the early efficacy data and favorable safety profile of NKTR-214 plus nivolumab, PROPEL will evaluate the clinical benefit, safety and tolerability of NKTR-214 combined with pembrolizumab or atezolizumab. Methods: PROPEL (NCT03138889) will enroll approximately 60 pts in 2 separate arms concurrently. The first arm will evaluate NKTR-214 plus pembrolizumab in up to 30 select pts with locally advanced or mM, mNSCLC, or locally advanced or metastatic urothelial bladder cancer (UBC) within the FDA-approved pembrolizumab indications and dosage regimen. The second arm will evaluate NKTR-214 plus atezolizumab in up to 30 select pts with locally advanced or metastatic UBC or mNSCLC within the FDA-approved atezolizumab indications and dosage regimen. NKTR-214 is administered intravenously over 30 (±5) minutes every 3 weeks in an outpatient setting; the first studied dose of NKTR-214 will be 0.006 mg/kg. The primary objectives are to evaluate safety and tolerability and to define the maximum tolerated dose or recommended phase 2 dose of NKTR-214 combined with pembrolizumab or atezolizumab. The secondary objectives are to evaluate preliminary anti-tumor activity and efficacy by assessing overall survival and progression-free survival. In addition, the study will assess the immunological effects of treatment and the association between efficacy measures and PD-L1 expression in tumors. Treatment may continue beyond progression if there is clinical benefit as determined by the investigator. Enrollment is ongoing in the U.S. Clinical trial information: NCT03138889.