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NCT03704467

Phase Ib/II Study of Carboplatin + M6620 + Avelumab in PARPi-resistant Ovarian Cancer

Completed Phase 1 Results posted Last updated 13 November 2020
What this trial tests

Phase 1 trial testing M6620 in Ovarian Cancer in 3 participants. Completed in 6 November 2019.

Timeline
4 March 2019
Primary endpoint
6 November 2019
6 November 2019

Quick facts

Lead sponsorEMD Serono Research & Development Institute, Inc.
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment3
Start date4 March 2019
Primary completion6 November 2019
Estimated completion6 November 2019
Sites13 locations across Belgium, United Kingdom, United States

Drugs / interventions tested

Conditions studied

Sponsor

EMD Serono Research & Development Institute, Inc. — full company profile →

Who can join

18 and older, female only, with Ovarian Cancer. 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.

Part A: Number of Participants With Dose Limiting Toxicities (DLTs) Primary · Up to 3 weeks

DLT: any death not clearly due to underlying disease/extraneous causes/Grade(Gr) \>=3 nonhematologic/Gr\>=4 hematologic toxicity that was probably/definitely related to any of study interventions, individually/combination that occurred during DLT observation period, except for any of following: Gr3 infusion-related reaction; Transient (\<=6hr) Gr3 flu-like symptoms/fever, controlled with medical management; Transient (\<=72hr) Gr3 fatigue, local reactions, headache, nausea/emesis; Gr3 diarrhea, skin toxicity, liver function test increase; Single laboratory values out of normal range and contro

GroupValue95% CI
Part A: Carboplatin + M6620 + Avelumab0
Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs Secondary · Time from first dose of study treatment up to 230 days

An adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were defined as events that started or worsened after first dose of study intervent

TEAEs
GroupValue95% CI
Part A: Carboplatin + M6620 + Avelumab3
Treatment-Related TEAEs
GroupValue95% CI
Part A: Carboplatin + M6620 + Avelumab3
Part A: Number of Participants With Confirmed Best Overall Response (BOR) Secondary · Time from first dose of study treatment up to 230 days

Confirmed BOR according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and as assessed by an Investigator was defined as best response of any of the complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the date of randomization until disease progression/ recurrence (taking the smallest measurement recorded since the start of treatment as reference). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions

Complete Response
GroupValue95% CI
Part A: Carboplatin + M6620 + Avelumab0
Partial Response
GroupValue95% CI
Part A: Carboplatin + M6620 + Avelumab0
Stable Disease
GroupValue95% CI
Part A: Carboplatin + M6620 + Avelumab1
Progressive Disease
GroupValue95% CI
Part A: Carboplatin + M6620 + Avelumab2
Part A: Progression-Free Survival (PFS) Secondary · Time from first dose of study treatment up to 230 days

PFS according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and as assessed by an Investigator was defined as the time from date of randomization until date of the first observation of progressive disease (PD) or death due to any cause within 12 weeks of the last tumor assessment in the absence of documented PD, whichever occurs first. PD was defined as at least a 20% increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions.

Participant 1
GroupValue95% CI
Part A: Carboplatin + M6620 + Avelumab1.9
Participant 2
GroupValue95% CI
Part A: Carboplatin + M6620 + Avelumab2.1
Participant 3
GroupValue95% CI
Part A: Carboplatin + M6620 + Avelumab6.1
Part A: Time to Progression (TTP) Secondary · Time from first dose of study treatment up to 230 days

TTP according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and assessed by an Investigator was defined as the time from first dose of study intervention until progression disease (PD). PD was defined as at least a 20% increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. Participant wise data reported for this outcome measure.

Participant 1
GroupValue95% CI
Part A: Carboplatin + M6620 + Avelumab1.9
Participant 2
GroupValue95% CI
Part A: Carboplatin + M6620 + Avelumab2.1

Adverse events — posted to ClinicalTrials.gov

Time frame: Time from first dose of study treatment up to 230 days. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Part A: Carboplatin + M6620 + Avelumab
Serious: 1/3 (33%)
Deaths: 0/3

Serious adverse events (1 terms)

ReactionSystemPart A: Carboplatin + M662…
PyelonephritisInfections and infestations
Other adverse events (40 terms — click to expand)

ReactionSystemPart A: Carboplatin + M662…
NauseaGastrointestinal disorders
Abdominal painGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
FatigueGeneral disorders
Infusion related reactionInjury, poisoning and procedural complications
Back painMusculoskeletal and connective tissue disorders
InsomniaPsychiatric disorders
AnaemiaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
VertigoEar and labyrinth disorders
HypothyroidismEndocrine disorders
Vision blurredEye disorders
ConstipationGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
ToothacheGastrointestinal disorders
VomitingGastrointestinal disorders
Chest discomfortGeneral disorders
Peripheral swellingGeneral disorders
Drug hypersensitivityImmune system disorders
Tooth infectionInfections and infestations
Tooth fractureInjury, poisoning and procedural complications
Blood urine presentInvestigations
Lymphocyte count decreasedInvestigations
Platelet count decreasedInvestigations
White blood cell count decreasedInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
Flank painMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
HeadacheNervous system disorders
Neuropathy peripheralNervous system disorders
AnxietyPsychiatric disorders
Depressed moodPsychiatric disorders
Bladder painRenal and urinary disorders
HydronephrosisRenal and urinary disorders
CoughRespiratory, thoracic and mediastinal disorders
Night sweatsSkin and subcutaneous tissue disorders
PruritusSkin and subcutaneous tissue disorders
Pruritus generalisedSkin and subcutaneous tissue disorders

Most-reported serious reactions: Pyelonephritis.

Data from ClinicalTrials.gov NCT03704467 adverse events section.

Sponsor's own description

The study was to evaluate the efficacy and safety of avelumab in combination with M6620 + carboplatin in participants with PARPi-resistant, recurrent, platinum sensitive ovarian, primary peritoneal, or fallopian tube cancer.

Publications & conference data

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

  1. Tumor Microenvironment in Ovarian Cancer: Function and Therapeutic Strategy.
    Yang Y, Yang Y, Yang J, Zhao X, et al · · 2020 · cited 168× · PMID 32850861 · DOI 10.3389/fcell.2020.00758
  2. Drug resistance in ovarian cancer: from mechanism to clinical trial.
    Wang L, Wang X, Zhu X, Zhong L, et al · · 2024 · cited 139× · PMID 38539161 · DOI 10.1186/s12943-024-01967-3
  3. Progress towards a clinically-successful ATR inhibitor for cancer therapy.
    Barnieh FM, Loadman PM, Falconer RA. · · 2021 · cited 97× · PMID 34909652 · DOI 10.1016/j.crphar.2021.100017
  4. Cell cycle checkpoints and beyond: Exploiting the ATR/CHK1/WEE1 pathway for the treatment of PARP inhibitor-resistant cancer.
    Gupta N, Huang TT, Horibata S, Lee JM. · · 2022 · cited 89× · PMID 35259479 · DOI 10.1016/j.phrs.2022.106162
  5. Targeting the replication stress response through synthetic lethal strategies in cancer medicine.
    Ngoi NYL, Pham MM, Tan DSP, Yap TA. · · 2021 · cited 78× · PMID 34215565 · DOI 10.1016/j.trecan.2021.06.002
  6. Participation of the ATR/CHK1 pathway in replicative stress targeted therapy of high-grade ovarian cancer.
    Gralewska P, Gajek A, Marczak A, Rogalska A. · · 2020 · cited 68× · PMID 32316968 · DOI 10.1186/s13045-020-00874-6
  7. Emerging strategies for cancer therapy by ATR inhibitors.
    Yano K, Shiotani B. · · 2023 · cited 42× · PMID 37189251 · DOI 10.1111/cas.15845
  8. Harnessing DNA Replication Stress for Novel Cancer Therapy.
    Zhu H, Swami U, Preet R, Zhang J. · · 2020 · cited 30× · PMID 32854236 · DOI 10.3390/genes11090990

Verify or expand the search:

Other trials of M6620

Trials testing the same drug.

Other recruiting trials for Ovarian Cancer

Currently open trials in the same condition.

Other EMD Serono Research & Development Institute, Inc. trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03704467.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing