Clinical trial · Interventional
A Study of GDC-0575 Alone and in Combination With Gemcitabine in Participants With Refractory Solid Tumors or Lymphoma
An Open-label, Phase I, Dose Escalation Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GDC-0575 Administered Alone and in Combination With Gemcitabine in Patients With Refractory Solid Tumors or Lymphoma
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This open-label, multicenter, Phase I, dose-escalation study will evaluate the safety, tolerability, and pharmacokinetics (PK) of GDC-0575 administered alone or in combination with gemcitabine in participants with refractory solid tumors or lymphoma. In Stage 1, cohorts of participants will receive multiple ascending oral doses of GDC-0575 alone or in combination with intravenous gemcitabine. In Stage 2, participants will receive GDC-0575 orally in combination with intravenous gemcitabine at or below the maximum tolerated dose determined in Stage 1. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs, up to approximately 5 years.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Lymphoma, Solid Tumor | Lymphoma | ONTOLOGY_EXACT | 0.85 |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| GDC-0575 | Drug | — | UNRESOLVED |
| Gemcitabine | Drug | Gemcitabine | ALIAS |
Design
Arms and outcomes
Arms (4)
- type
- EXPERIMENTAL
- label
- Stage 1 Arm 1: GDC-0575 Monotherapy
- description
- Participants will receive escalating doses of GDC-0575, administered orally, for 3 consecutive days, starting on Days 1, 8, and 15 of each 21-day cycle.
- interventionNames
- Drug: GDC-0575
- type
- EXPERIMENTAL
- label
- Stage 1 Arm 2a: GDC-0575 + Gemcitabine (750 or 1000 mg/m^2)
- description
- Participants will receive gemcitabine 750 milligrams per meter square (mg/m\^2) or 1000 mg/m\^2, intravenously, on Days 1 and 8 followed by escalating doses of GDC-0575 orally, on Days 2 and 9 of each 21-day cycle.
- interventionNames
- Drug: GDC-0575
- Drug: Gemcitabine
- type
- EXPERIMENTAL
- label
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 * Histologically or cytologically documented, locally advanced or metastatic solid tumors or lymphoma for which standard therapy either does not exist or has proven ineffective or intolerable * Life expectancy greater than or equal to (\>=) 12 weeks, in the opinion of the investigator * Adequate hematologic, liver, and renal function * For Stage 2: Participants with human epidermal growth factor receptor 2 (HER2) negative, estrogen-receptor (ER) negative, and progesterone-receptor (PR) negative breast cancer * For Stage 2: Participants with non-mucinous, platinum-resistant ovarian cancer with documented radiographic progression or relapse according to RECIST within 6 months of receiving platinum-based chemotherapy * For Stage 2: Participants with histologically or cytologically confirmed diagnosis of squamous non-small cell lung cancer (NSCLC); mixed histology that is predominantly squamous is acceptable Exclusion Criteria: * History of prior significant toxicity from a same class of agents as GDC-0575 or gemcitabine requiring discontinuation of treatment * All acute toxicities related to prior therapy must have resolved prior to study entry, except for alopecia and mild neuropathy * Current severe, uncontrolled systemic disease (including but not limited to clinically significant cardiovascular, pulmonary, or renal disease or ongoing or active infection) excluding the cancer under study * History of significant cardiac dysfunction * History of malabsorption or other condition that would interfere with enteral absorption * Known human immunodeficiency virus (HIV) infection * Pregnancy, lactation or breastfeeding * Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms * Current use of alpha-adrenergic receptor blockers For Combination Arm only: * Any contraindication to gemcitabine therapy * More than two regimens of cytotoxic chemotherapy for the treatment of locally advanced or metastatic cancer * History of receiving high-dose chemotherapy requiring bone marrow or stem cell support * Irradiation to more than 25% of bone marrow-bearing areas
References
Publications (1)
- DERIVEDItaliano A, Infante JR, Shapiro GI, Moore KN, LoRusso PM, Hamilton E, Cousin S, Toulmonde M, Postel-Vinay S, Tolaney S, Blackwood EM, Mahrus S, Peale FV, Lu X, Moein A, Epler J, DuPree K, Tagen M, Murray ER, Schutzman JL, Lauchle JO, Hollebecque A, Soria JC. Phase I study of the checkpoint kinase 1 inhibitor GDC-0575 in combination with gemcitabine in patients with refractory solid tumors. Ann Oncol. 2018 May 1;29(5):1304-1311. doi: 10.1093/annonc/mdy076. PMID 29788155