Related Experiment Video
Updated: Jan 25, 2026
A Procedure to Study Stress-Induced Relapse of Heroin Seeking after Punishment-Imposed Abstinence
Published on: March 23, 2022
Durvalumab in Combination with Olaparib in Patients with Relapsed SCLC: Results from a Phase II Study
Anish Thomas1, Rasa Vilimas1, Christopher Trindade2
1Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
Purpose:
Despite high tumor mutationburden, immune checkpoint blockade has limited efficacy in SCLC. We hypothesized that poly (ADP-ribose) polymerase inhibition could render SCLC more susceptible to immune checkpoint blockade.
Methods:
A single-arm, phase II trial (NCT02484404) enrolled patients with relapsed SCLC who received durvalumab, 1500 mg every 4 weeks, and olaparib, 300 mg twice a day. The primary outcome was objective response rate. Correlative studies included mandatory collection of pretreatment and during-treatment biopsy specimens, which were assessed to define SCLC immunephenotypes: desert (CD8-positive T-cell prevalence low), excluded (CD8-positive T cells in stroma immediately adjacent/within tumor), and inflamed (CD8-positive T cells in direct contact with tumor).
Results:
A total of 20 patients were enrolled. Their median age was 64 years, and most patients (60%) had platinum-resistant/refractory disease. Of 19 evaluable patients, two were observed to have partial or complete responses (10.5%), including a patient with EGFR-transformed SCLC. Clinical benefit was observed in four patients (21.1% [95% confidence interval: 6.1%-45.6%]) with confirmed responses or prolonged stable disease (≥8 months). The most common treatment-related adverse events were anemia (80%), lymphopenia (60%), and leukopenia (50%). Nine of 14 tumors (64%) exhibited an excluded phenotype; 21% and 14% of tumors exhibited the inflamed and desert phenotypes, respectively. Tumor responses were observed in all instances in which pretreatment tumors showed an inflamed phenotype. Of the five tumors without an inflamed phenotype at baseline, no during-treatment increase in T-cell infiltration or programmed death ligand 1 expression on tumor-infiltrating immune cells was observed.
Conclusions:
The study combination did not meet the preset bar for efficacy. Pretreatment and during-treatment biopsy specimens suggested that tumor immune phenotypes may be relevant for SCLC responses to immune checkpoint blockade combinations. The predictive value of preexisting CD8-positive T-cell infiltrates observed in this study needs to be confirmed in larger cohorts.
Insights
This study combined poly (ADP-ribose) polymerase inhibition with immune checkpoint blockade in small cell lung cancer (SCLC). The combination showed limited efficacy, but tumor immune phenotypes may predict response to immunotherapy.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Small cell lung cancer (SCLC) has high tumor mutation burden but limited response to immune checkpoint blockade.
- Poly (ADP-ribose) polymerase (PARP) inhibition is being investigated to enhance immunotherapy efficacy.
Purpose of the Study:
- To evaluate the efficacy of combining durvalumab (immune checkpoint blockade) with olaparib (PARP inhibitor) in patients with relapsed SCLC.
- To explore the relationship between SCLC immune phenotypes and response to the combination therapy.
Main Methods:
- A single-arm, phase II clinical trial (NCT02484404) enrolled 20 patients with relapsed SCLC.
- Patients received durvalumab and olaparib. Pretreatment and on-treatment biopsies were analyzed to define tumor immune phenotypes (desert, excluded, inflamed).
Main Results:
- The combination therapy did not meet the primary efficacy endpoint. Objective response rate was 10.5% in evaluable patients.
- Clinical benefit was observed in 21.1% of patients. An inflamed phenotype at baseline correlated with tumor response.
- Common adverse events included anemia, lymphopenia, and leukopenia.
Conclusions:
- The combination of durvalumab and olaparib did not demonstrate significant efficacy in relapsed SCLC.
- Tumor immune phenotypes, particularly the inflamed phenotype, may be predictive of response to immune checkpoint blockade combinations in SCLC.
- Further validation in larger cohorts is needed to confirm the predictive value of CD8-positive T-cell infiltrates.
Related Concept Videos
02:39Phase Diagrams
02:31Phase Transitions
01:15Bioavailability Study Design: Healthy Subjects Versus Patients
01:28Inductance: Single-Phase And Three-Phase Line
Single-Phase Two-Wire Line:
A single-phase line consists of two solid cylindrical conductors, denoted as x and y. Each conductor carries phasor currents ix and iy, respectively. Given that the sum of these currents is...
01:25Capacitance: Single-Phase And Three-Phase Line
Single-Phase Lines
Consider a single-phase, two-wire transmission line with equal phase spacing energized by a voltage source. One conductor carries a uniform positive charge, while the other carries an equal negative charge. The capacitance C of the line can be derived from the voltage V between the conductors. For a one-meter section of the line, the capacitance is given...
01:19Phase Changes
A substance melts or freezes at a temperature called its melting point and boils or condenses at its boiling point. These temperatures depend on pressure. High pressure favors the denser form of the substance, so typically, high pressure...