Phase 1b study of berzosertib and cisplatin in patients with advanced triple-negative breast cancer.

Platinum derivatives are commonly used for the treatment of patients with metastatic triple-negative breast cancer (TNBC). However, resistance often develops, leading to treatment failure. This expansion cohort (part C2) of the previously reported phase 1b trial (NCT02157792) is based on the recommended phase 2 dose of the combination of the ataxia-telangiectasia and Rad3-related (ATR) inhibitor berzosertib and cisplatin observed in patients with advanced solid tumors, including TNBC.

Pharmacokinetic Interaction Between the MEK1/MEK2 Inhibitor Trametinib and Oral Contraceptives Containing Norethindrone and Ethinyl Estradiol in Female Patients With Solid Tumors.

This phase 1 postapproval study assessed the effect of the mitogen-activated protein kinase kinase enzyme 1/enzyme 2 inhibitor trametinib (2 mg once daily, repeat dosing) on the pharmacokinetics of combined oral contraceptives (COCs) containing norethindrone (NE; 1 mg daily) and ethinyl estradiol (EE; 0.035 mg daily) in 19 female patients with solid tumors. Compared with NE/EE administered without trametinib, NE/EE administered with steady-state trametinib was associated with a clinically nonrelevant 20% increase in NE exposure (area under the curve [AUC]) and no effect on EE exposure (geometric mean ratio [geo-mean] of NE/EE + trametinib to NE/EE [90%CI]: NE AUC calculated to the end of a dosing interval at steady-state [AUC ] 1.

Preservation of quality of life in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer treated with tucatinib or placebo when added to trastuzumab and capecitabine (HER2CLIMB trial).

Aims: In HER2CLIMB, tucatinib significantly improved progression-free and overall survival in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer. We evaluated the impact of tucatinib on health-related quality of life (HR-QoL) in HER2CLIMB.

Methods: Patients were randomised 2:1 to tucatinib or placebo combined with trastuzumab and capecitabine.

Ramucirumab in Combination with Pembrolizumab in Treatment-Naïve Advanced Gastric or GEJ Adenocarcinoma: Safety and Antitumor Activity from the Phase 1a/b JVDF Trial.

Ramucirumab (anti-VEGFR2) plus pembrolizumab (anti-PD1) demonstrated promising antitumor activity and tolerability among patients with previously treated advanced cancers, supporting growing evidence that combination therapies modulating the tumor microenvironment may expand the spectrum of patients who respond to checkpoint inhibitors. Here we present the results of this combination in first-line patients with metastatic G/GEJ cancer. Twenty-eight patients (≥18 years) with no prior systemic chemotherapy in the advanced/metastatic setting received ramucirumab (8 mg/kg days 1 and 8) plus pembrolizumab (200 mg day 1) every 3 weeks as part of JVDF phase 1a/b study.

Encorafenib, Binimetinib, and Cetuximab in V600E-Mutated Colorectal Cancer.

Background: Patients with metastatic colorectal cancer with the V600E mutation have a poor prognosis, with a median overall survival of 4 to 6 months after failure of initial therapy. Inhibition of BRAF alone has limited activity because of pathway reactivation through epidermal growth factor receptor signaling.

Methods: In this open-label, phase 3 trial, we enrolled 665 patients with V600E-mutated metastatic colorectal cancer who had had disease progression after one or two previous regimens.

A phase 1, open-label, dose-escalation trial of oral TSR-011 in patients with advanced solid tumours and lymphomas.

Background: Anaplastic lymphoma kinase (ALK) gene rearrangements are oncogenic drivers in non-small-cell lung cancer (NSCLC). TSR-011 is a dual ALK and tropomyosin-related kinase (TRK) inhibitor, active against ALK inhibitor resistant tumours in preclinical studies. Here, we report the safety, tolerability and recommended phase 2 dose (RP2D) of TSR-011 in patients with relapsed or refractory ALK- and TRK-positive advanced cancers.