NCT03087019

Pembrolizumab With or Without Radiation in Patients With Recurrent or Metastatic Adenoid Cystic Carcinoma

Completed Phase 2 Results posted Last updated 14 October 2022

What this trial tests

Phase 2 trial testing Radiation in Adenoid Cystic Carcinoma in 21 participants. Completed in 4 August 2020.

Timeline

25 April 2017

Primary endpoint
4 August 2020

4 August 2020

Quick facts

Lead sponsor	Dana-Farber Cancer Institute
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	21
Start date	25 April 2017
Primary completion	4 August 2020
Estimated completion	4 August 2020
Sites	2 locations across United States

Drugs / interventions tested

• Radiation
• Pembrolizumab (pembrolizumab) — full drug profile →

Conditions studied

• Adenoid Cystic Carcinoma — all drugs for Adenoid Cystic Carcinoma →

Sponsor

Dana-Farber Cancer Institute

Who can join

18 and older, any sex, with Adenoid Cystic Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Patients Demonstrating Objective Response In Non-Irradiated Lesions (Tumor Size on Scans) Primary · 2 years

Objective response will be assessed in non-irradiated lesions among all eligible and treated patients pursuing RECIST 1.1. Per RECIST guidelines for target lesions, Complete Response (CR): disappearance of all target lesions; Partial Response (PR): \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): \>20% increase in sum of the longest diameter (LD) of measured lesions, referencing the smallest sum LD, or new lesions; Stable Disease (SD): neither PR nor PD. Objective response refers to tumor shrinkage at least qualifying as PR.

Group	Value	95% CI
Pembrolizumab + Radiation	0
Pembrolizumab	0

Progression Free Survival (Time From Randomization to Disease Progression or Death) Secondary · 2 years

Progression-free survival is defined as the time from randomization to disease progression or death, whichever occurs first. Patients who are alive without disease progression will be censored at the date of last disease assessment. Progression-free survival will be evaluated using both RECIST 1.1 and immune-related response criteria (irRC), and both sets of results will be reported in each arm. Per RECIST criteria, progression is defined as a \>=20% increase in the sum of the longest diameter of the measured lesions, referencing the smallest longest diameter sum, or the appearance of at least

Group	Value	95% CI
Pembrolizumab + Radiation	4.5	2.4 – 20.6
Pembrolizumab	6.6	2.4 – 13.1

Overall Survival (Time From Randomization to Death) Secondary · 2 years

Overall survival is defined as the time from randomization to death or date last known alive. Overall survival will be evaluated using both RECIST 1.1 and immune-related response criteria (irRC), and both sets of results will be reported in each arm. will be evaluated using both RECIST 1.1 and immune-related response criteria (irRC), and both sets of results will be reported in each arm.

Group	Value	95% CI
Pembrolizumab + Radiation	NA	10.1 – NA
Pembrolizumab	27.2	22.9 – NA

Number of Participants With Complete Response (Absence of Non-irradiated Lesions on Scans) Secondary · 2 years

Complete disappearance of all measurable non-irradiated lesions. All lymph nodes must be non-pathological in size (\<10 mm short axis).

Group	Value	95% CI
Pembrolizumab + Radiation	0
Pembrolizumab	0

Number of Participants With Partial Response (Tumor Size on Scans) Secondary · 2 years

At least a 30% decrease in the longest diameter valuated using RECIST 1.1.

Group	Value	95% CI
Pembrolizumab + Radiation	0
Pembrolizumab	0

Number of Treatment-Emergent Adverse Events Secondary · 2 years

All patients who receive treatment, regardless of eligibility, will be evaluable for toxicity. Toxicity will be graded according to NCI CTCAE, Version 4.0. The proportions of patients with various toxicities will be reported by treatment arm.

Group	Value	95% CI
Pembrolizumab + Radiation	51
Pembrolizumab	24

Adverse events — posted to ClinicalTrials.gov

Time frame: 2 years. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pembrolizumab + Radiation

Serious: 3/10 (30%)

Deaths: 1/10

Pembrolizumab

Serious: 4/10 (40%)

Deaths: 1/10

Serious adverse events (15 terms)

Reaction	System	Pembrolizumab + Radiation	Pembrolizumab
Wound Infection	Infections and infestations	—	—
Hyperthydroidism	Endocrine disorders	—	—
Pneumonia	Respiratory, thoracic and mediastinal disorders	—	—
Dysphagia	Gastrointestinal disorders	—	—
Elevated ALT	Investigations	—	—
Elevated AST	Investigations	—	—
Elevated Alkaline Phosphatase	Investigations	—	—
Elevated Total Bilirubin	Investigations	—	—
Aspiration Pneumonia	Respiratory, thoracic and mediastinal disorders	—	—
Diarrhea	Gastrointestinal disorders	—	—
Generalized Muscle Weakness	Musculoskeletal and connective tissue disorders	—	—
Chest Tightness	General disorders	—	—
Paresthesia (tongue)	Nervous system disorders	—	—
Confusion	Psychiatric disorders	—	—
Movement Disorder (tongue and lips)	Nervous system disorders	—	—

Other adverse events (36 terms — click to expand)

Reaction	System	Pembrolizumab + Radiation	Pembrolizumab
Diarrhea	Gastrointestinal disorders	—	—
Fatigue	General disorders	—	—
Skin/Subcutaneous Tissue Disorders - Other	Skin and subcutaneous tissue disorders	—	—
Pneumonitis	Respiratory, thoracic and mediastinal disorders	—	—
Alanine Aminotransferase Increased	Investigations	—	—
Aspartate Aminotransferase Increased	Investigations	—	—
Endocrine Disorders - Other	Endocrine disorders	—	—
Hypothyroidism	Endocrine disorders	—	—
Musculoskeletal and Connective Tissue Disorder - Other	Musculoskeletal and connective tissue disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Alkaline Phosphatase Increased	Investigations	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—
Anorexia	Metabolism and nutrition disorders	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Back Pain	Musculoskeletal and connective tissue disorders	—	—
Chills	General disorders	—	—
Creatinine Increased	Investigations	—	—
Dry Mouth	Gastrointestinal disorders	—	—
Dysgeusia	Nervous system disorders	—	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—	—
Gastroesophageal Reflux Disease	Gastrointestinal disorders	—	—
Gastrointestinal Disorders - Other	Gastrointestinal disorders	—	—
General Disorders and Administration Site Conditions - Other	General disorders	—	—
Hepatobiliary Disorders - Other	Hepatobiliary disorders	—	—
Hypercalcemia	Metabolism and nutrition disorders	—	—
Hypertension	Vascular disorders	—	—
Hyperthyroidism	Endocrine disorders	—	—
Hyponatremia	Metabolism and nutrition disorders	—	—
Hypophosphatemia	Metabolism and nutrition disorders	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—
Neck Pain	Musculoskeletal and connective tissue disorders	—	—
Nervous System Disorders - Other	Nervous system disorders	—	—
Pain	General disorders	—	—
Pruritis	Skin and subcutaneous tissue disorders	—	—
Skin Hyperpigmentation	Skin and subcutaneous tissue disorders	—	—
Vomiting	Gastrointestinal disorders	—	—

Most-reported serious reactions: Wound Infection, Hyperthydroidism, Pneumonia, Dysphagia, Elevated ALT, Elevated AST, Elevated Alkaline Phosphatase, Elevated Total Bilirubin.

Data from ClinicalTrials.gov NCT03087019 adverse events section.

Sponsor's own description

This research study is studying immunotherapy with or without radiation therapy as a possible treatment for adenoid cystic carcinoma.

The immunotherapy involved in this study is:

* Pembrolizumab (MK-3475 or KEYTRUDA).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. A Randomized Phase 2 Study of Pembrolizumab With or Without Radiation in Patients With Recurrent or Metastatic Adenoid Cystic Carcinoma.
   Mahmood U, Bang A, Chen YH, Mak RH, et al · · 2021 · cited 86× · PMID 32781104 · DOI 10.1016/j.ijrobp.2020.08.018
2. Combination Strategies to Augment Immune Check Point Inhibitors Efficacy - Implications for Translational Research.
   Varayathu H, Sarathy V, Thomas BE, Mufti SS, et al · · 2021 · cited 62× · PMID 34123767 · DOI 10.3389/fonc.2021.559161
3. Optimizing the Treatment Schedule of Radiotherapy Combined With Anti-PD-1/PD-L1 Immunotherapy in Metastatic Cancers.
   Kong Y, Ma Y, Zhao X, Pan J, et al · · 2021 · cited 34× · PMID 33859942 · DOI 10.3389/fonc.2021.638873
4. Combination therapy with PD-1/PD-L1 blockade: An overview of ongoing clinical trials.
   Johnson CB, Win SY. · · 2018 · cited 26× · PMID 29632719 · DOI 10.1080/2162402x.2017.1408744
5. Salivary glands adenoid cystic carcinoma: a molecular profile update and potential implications.
   da Silva FJ, Carvalho de Azevedo J, Ralph ACL, Pinheiro JJV, et al · · 2023 · cited 18× · PMID 37476370 · DOI 10.3389/fonc.2023.1191218
6. PD-L1 and PD-L2 Expression Levels Are Low in Primary and Secondary Adenoid Cystic Carcinomas of the Orbit: Therapeutic Implications.
   Wolkow N, Jakobiec FA, Afrogheh AH, Kidd M, et al · · 2020 · cited 15× · PMID 31990894 · DOI 10.1097/iop.0000000000001585
7. The endoscopic endonasal approach for sinonasal and nasopharyngeal adenoid cystic carcinoma.
   Kashiwazaki R, Turner MT, Geltzeiler M, Fernandez-Miranda JC, et al · · 2020 · cited 15× · PMID 31194275 · DOI 10.1002/lary.28100
8. Adenoid cystic carcinoma: insights from molecular characterization and therapeutic advances.
   Jia Y, Liu Y, Yang H, Yao F. · · 2024 · cited 7× · PMID 39263605 · DOI 10.1002/mco2.734