Skip to main content
OpenTrials
Completed

NCT Number: NCT02807844

Phase Ib/II Study of MCS110 in Combination With PDR001 in Patients With Advanced Malignancies

The purpose of this study of MCS110 with PDR001 was to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of the combination of MCS110 with PDR001 in adult patients with solid tumors.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Triple Negative Breast Cancer Breast Diseases Breast Neoplasms Digestive System Diseases Digestive System Neoplasms Endocrine Gland Neoplasms Endocrine System Diseases Endometrial Carcinoma Endometrial Neoplasms Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Melanoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Pancreatic Carcinoma Pancreatic Diseases Pancreatic Neoplasms Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases Triple Negative Breast Neoplasms Urogenital Diseases Urogenital Neoplasms Uterine Diseases Uterine Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Novartis Investigative Site, Wilrijk, Belgium

Loading trial locations.

About this study

Combined treatment with MCS110 and PDR001 was expected to result in Tumor-associated macrophages (TAM) depletion, enhanced T-cell activation and synergistic antitumor activity in the clinical setting.

This study was a Phase Ib/II, multi-center, open label study starting with a Phase Ib dose escalation part followed by a Phase II part. MCS110 and PDR001 were administered i.v. Q3W until the patient experienced unacceptable toxicity, progressive disease as per irRC and/or treatment was discontinued at the discretion of the investigator or the patient. Patients were not to discontinue treatment based on progressive disease per Response evaluation criteria in solid tumors (RECIST) v1.1. During the Phase Ib part of the study, cohorts of patients were treated with increasing doses of MCS110 and PDR001 every 3 weeks until a Recommended Phase 2 Dose (RP2D) was determined for this treatment combination.

To assure that the combination RP2D did not exceed the Maximum tolerated dose (MTD), the combination MCS110 and PDR001 dose escalation was guided by a Bayesian logistic regression model (BLRM) with overdose control (EWOC) principle based on dose limiting toxicity data in the context of available safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) information. Once the MTD and/or RP2D was declared, additional patients were enrolled in the Phase II part in order to assess the preliminary anti-tumor activity of MCS110 in combination with PDR001 in anti-PD1/PD-L1-naive triple negative breast cancer (TNBC), pancreatic (PC), endometrial carcinoma (EC) and anti PD1/PD-L1-resistance melanoma (ME).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Main Inclusion Criteria:

  • Signed informed consent prior to any procedures
  • Phase Ib part: Adult patients with advanced melanoma, endometrial carcinoma, pancreatic or TNBC, with measurable or non-measurable disease who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists.
  • Phase II part: Adult patients with advanced solid tumors who have received standard therapy (no more than 3 prior lines of treatment) or are intolerant of standard therapy, have progressed following their last prior therapy, and fit into one of the following groups:
  • Group 1: TNBC who did not receive prior anti-PD-1/PD-L1 treatment
  • Group 2: Pancreatic adenocarcinoma who did not receive prior anti-PD-1/PD-L1 treatment
  • Group 3: Endometrial carcinoma who did not receive prior anti-PD-1/PD-L1 treatment
  • Group 4: Melanoma who progressed on prior anti-PD-1/PD-L1 treatment.

Main Exclusion Criteria:

  • Patients with the following:
  • Symptomatic central nervous system (CNS) metastases or those requiring local CNS-directed therapy.
  • Abnormal liver, renal, or blood lab values.
  • Impaired cardiac function or clinically significant cardiac disease.
  • Active autoimmune disease or documented autoimmune disease within 3 years of screening.
  • Active infection requiring antibiotic therapy.
  • Known HIV, active hepatitis B or C virus.
  • Concurrent malignant disease.
  • Patients who received systemic anticancer therapy, major surgery, or radiotherapy within 2 weeks of study treatment, or live vaccines within 4 weeks of study treatment.
  • Patients requiring chronic treatment with systemic steroid therapy or any immunosuppressive therapy.
  • Patients who used hematopoietic colony-stimulating growth factors within 2 weeks of study treatment.

Treatment and study plan

MCS110

Drug

MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.

Other names: colony-stimulating factor-1 [CSF-1])

PDR001

Drug

MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.

Primary outcomes

  1. Phase Ib: Percentage of Participants With Adverse Events, as a Measure of Safety

    Time frame: From start of treatment to a maximum timeframe of 116.4 weeks for phase Ib

    Phase Ib: To characterize the safety and tolerability of MCS110 in combination with PDR001 in patients with advanced solid malignancies and to identify a recommended dose combination for Phase II.

  2. Phase II : Overall Response Rate (ORR) - Per RECIST v1.1

    Time frame: 4 years

    Overall Response Rate (ORR) is defined as the proportion of patients with a best overall response assessed by CT scan or MRI of complete response (CR), disappearance of all measurable and non-measurable lesions or partial response (PR), at least a 30% decrease in the sum of diameter of all measurable lesions, taking as reference the baseline sum of diameters,. based on local Investigator assessment, as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1)

  3. Phase II : Bayesian Inference of Overall Response Rate (ORR) - Per RECIST v1.1 - Mean

    Time frame: 4 years

    Overall Response Rate (ORR) is defined as the proportion of patients with a best overall response assessed by CT scan or MRI of complete response (CR), disappearance of all measurable and non-measurable lesions or partial response (PR), at least a 30% decrease in the sum of diameter of all measurable lesions, taking as reference the baseline sum of diameters,. based on local Investigator assessment, as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) - mean (FAS)

  4. Phase II: Clinical Benefit Rate (Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) > 4 Month)) - Per RECIST v1.1

    Time frame: 4 years

    Phase II: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) per investigator based on Response evaluation criteria in solid tumors (RECIST) v1.1

  5. Phase II: Bayesian Inference of Clinical Benefit Rate - Per RECIST v1.1- Mean

    Time frame: 4 years

    Phase II: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) per investigator based on Response evaluation criteria in solid tumors (RECIST) v1.1

  6. Phase Ib: Planned Dose Intensity - MCS110

    Time frame: Measured up to a max of 112.4 weeks

    To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II. Planned dose intensity for MCS110 is cumulative planned dose (mg/kg)/ number of doses scheduled per protocol during treatment period (i.e., this is equivalent to planned dose level).

  7. Phase Ib: Relative Dose Intensity - MCS110

    Time frame: Measured up to a max of 112.4 weeks

    To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II. Relative dose intensity (%) is 100 × dose intensity (mg/kg/3wks)/planned dose intensity (mg/kg/3wks).

  8. Phase Ib: Planned Dose Intensity - PDR001

    Time frame: Measured up to a max of 112.4 weeks

    To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II. Planned dose intensity for PDR001 (mg/3wks) is planned cumulative dose (mg)/ number of doses scheduled per protocol during treatment period (i.e., this is equivalent to planned dose level).

  9. Phase Ib: Relative Dose Intensity - PDR001

    Time frame: Measured up to a max of 112.4 weeks

    To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II. Relative dose intensity (%) is 100 × dose intensity (mg/3wks)/planned dose intensity (mg/3wks).

  10. Phase Ib: Number of Participants With Dose Reductions

    Time frame: Measured up to a max of 112.4 weeks

    To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II.

  11. Phase Ib: Number of Dose Interruptions Per Participant

    Time frame: Measured up to a max of 112.4 weeks

    To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II.

  12. Phase Ib: Number of Subjects With at Least One Dose Interruption

    Time frame: Measured up to a max of 112.4 weeks

    To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II.

  13. Phase Ib: Number of Participants With Dose Limiting Toxicities (DLTs) During the First 2 Cycles of Study Treatment

    Time frame: the first 2 cycles of study treatment; cycle = 21 days (i.e., at day 42)

    Phase Ib: Dose limiting toxicities occurring during the first 2 cycles by system organ class, preferred term and maximum grade for Phase Ib. The National Cancer Institute Common Terminology Criteria for Adverse events (NCI CTCAE) version 4.03 was used for all grading.

Secondary outcomes

  1. Phase II : Overall Response Rate (ORR) - Per irRC

    Time frame: 4 years

    Phase II: Overall Response Rate (Complete response (CR) or Partial response (PR)) (with confirmation) as per investigator based on immune related Response criteria (irRC) (FAS)

  2. Phase Ib: Overall Response Rate (ORR)

    Time frame: 4 years

    Phase Ib: Overall Response Rate (Complete response (CR) or Partial response (PR)), per RECIST v1.1 and per immune related Response criteria (irRC)

  3. Phase II : Bayesian Inference of Overall Response Rate (ORR) - Per irRC - Mean

    Time frame: 4 years

    Phase II: Overall Response Rate (Complete response (CR) or Partial response (PR)) (with confirmation) as per investigator based on immune related Response criteria (irRC)- mean (FAS)

  4. Phase 1b: Clinical Benefit Rate (CBR)

    Time frame: 4 years

    Phase 1b: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) per RECIST v1.1 and per immune related Response criteria (irRC)

  5. Phase II: Clinical Benefit Rate (Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) > 4 Month)) - Per irRC

    Time frame: 4 years

    Phase II: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) per immune related Response criteria (irRC)

  6. Phase II: Bayesian Inference of Clinical Benefit Rate - Per irRC - Mean

    Time frame: 4 years

    Phase II: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) per investigator based on immune related Response criteria (irRC)- mean (FAS)

  7. Phase 1b and Phase II: Progression Free Survival Based on Investigator Assessment as Per RECIST v1.1 and Per Immune Related Response Criteria (irRC) - Using Kaplan-Meier Method - Median

    Time frame: Up to year 4

    Phase 1b and Phase II: Progression Free Survival. Progression is defined as a 20% increase in the sum of diameter of measurable lesions taking as reference the smallest sum of diameter recorded at or after baseline, or worsening of non-measurable lesions or the appearance of new lesions, using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) or Per Immune Related Response Criteria (irRC). Unlike RECIST 1.1, PD per irRC requires confirmation at a new assessment after at least 4 weeks - using Kaplan-Meier method - Median.

  8. Phase 1b and Phase II: Overall Survival - Using Kaplan-Meier Method - Median

    Time frame: Up to year 4

    Phase 1b and Phase II: Overall Survival - using Kaplan-Meier method - Median

  9. Phase 1b and Phase II: Duration of Response (DOR)

    Time frame: 4 years

    Phase 1b and Phase II: Duration of Response (DOR) per RECIST v1.1 and per immune related Response criteria (irRC)

  10. Phase 1b and Phase II: Disease Control Rate (DCR)

    Time frame: 4 years

    Phase 1b and Phase II: Disease Control Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) per RECIST v1.1 and per immune related Response criteria (irRC)

  11. Phase II: Percentage of Participants With Adverse Events, as a Measure of Safety

    Time frame: From start of treatment to a maximum timeframe of 92.4 weeks for phase II.

    Phase II: To further characterize the safety and tolerability of MCS110 given in combination with PDR001

  12. Phase Ib and Phase II: Immunogenicity MCS110

    Time frame: 4 years

    Phase Ib and Phase II: Presence of anti-MCS110 antibodies

  13. Phase Ib and Phase II: Immunogenicity PDR001

    Time frame: 4 years

    Phase Ib and Phase II: Presence of anti-PDR001 antibodies

  14. Phase Ib and Phase II: Pharmacokinetics of MCS110 - AUClast and AUCinf

    Time frame: cycle 1 (day 21) and cycle 4 (day 84)

    Phase Ib and Phase II: PK Parameters - AUClast, which is the AUC from time zero to the last measurable concentration sampling time (tlast) (mass × time

    × volume-1); and AUCinf, which is the AUC from time zero to infinity (mass × time × volume-1) - MCS110

  15. Phase Ib and Phase II: Pharmacokinetics of PDR001 - AUClast and AUCinf

    Time frame: cycle 1 (day 21) and cycle 4 (day 84)

    Phase Ib and Phase II: Pharmacokinetics (PK) Parameters - AUClast, which is the AUC from time zero to the last measurable concentration sampling time (tlast) (mass × time

    × volume-1); and AUCinf, which is the AUC from time zero to infinity (mass × time × volume-1) and AUCinf - PDR001

  16. Phase Ib and Phase II: Pharmacokinetics of MCS110 - Cmax and Clast

    Time frame: cycle 1 (day 21) and cycle 4 (day 84)

    Phase Ib and Phase II: PK Parameters - Cmax, which is the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass × volume-1); and Clast - MCS110

  17. Phase Ib and Phase II: Pharmacokinetics of PDR001 - Cmax and Clast

    Time frame: cycle 1 (day 21) and cycle 4 (day 84)

    Phase Ib and Phase II: PK Parameters - Cmax, which is the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass × volume-1); and Clast - PDR001

  18. Phase Ib and Phase II: Pharmacokinetics of MCS110 - Tmax

    Time frame: cycle 1 (day 21) and cycle 4 (day 84)

    Phase Ib and Phase II: PK Parameters - Tmax, which is the time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time) - MCS110

  19. Phase Ib and Phase II: Pharmacokinetics of PDR001 - Tmax

    Time frame: cycle 1 (day 21) and cycle 4 (day 84)

    Phase Ib and Phase II: PK Parameters - Tmax, which is the time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time) - PDR001

  20. Phase Ib and Phase II: Pharmacokinetics of MCS110 - T1/2

    Time frame: cycle 1 (day 21) and cycle 4 (day 84)

    Phase Ib and Phase II: PK Parameters - T1/2, which is the terminal half-life associated with the terminal slope of a semi logarithmic concentration time curve (time) - MCS110

  21. Phase Ib and Phase II: Pharmacokinetics of PDR001 - T1/2

    Time frame: cycle 1 (day 21) and cycle 4 (day 84)

    Phase Ib and Phase II: PK Parameters - T1/2, which is the terminal half-life associated with the terminal slope of a semi logarithmic concentration time curve (time) - PDR001

  22. Phase Ib and Phase II: Pharmacokinetics of MCS110 - CL

    Time frame: cycle 1 (day 21) and cycle 4 (day 84)

    Phase Ib and Phase II: PK Parameters - CL, which is the total body clearance of drug from the plasma (volume × time-1) - MCS110

  23. Phase Ib and Phase II: Pharmacokinetics of PDR001 - CL

    Time frame: cycle 1 (day 21) and cycle 4 (day 84)

    Phase Ib and Phase II: PK Parameters - CL, which is the total body clearance of drug from the plasma (volume × time-1) - PDR001

  24. Phase Ib and Phase II: Pharmacokinetics of MCS110 - Vz

    Time frame: cycle 1 (day 21) and cycle 4 (day 84)

    Phase Ib and Phase II: PK Parameters - Vz, which is the apparent volume of distribution during terminal phase (volume) - MCS110

  25. Phase Ib and Phase II: Pharmacokinetics of PDR001 - Vz

    Time frame: cycle 1 (day 21) and cycle 4 (day 84)

    Phase Ib and Phase II: PK Parameters - Vz, which is the apparent volume of distribution during terminal phase (volume) - PDR001

  26. Phase Ib and Phase II: Pharmacokinetics of MCS110 - Accumulation Ratio (AR)

    Time frame: cycle 4 (day 84)

    Phase Ib and Phase II: PK Parameters - Accumulation ratio (AR), which is the AUClast (multiple Dose)/AUClast (single dose) (for cycle 4 only) - MCS110

  27. Phase Ib and Phase II: Pharmacokinetics of PDR001 - Accumulation Ratio (AR)

    Time frame: cycle 4 (day 84)

    Phase Ib and Phase II: PK Parameters - Accumulation ratio (AR), which is the AUClast (multiple Dose)/AUClast (single dose) (for cycle 4 only) - PDR001

  28. Phase Ib and Phase II: All Collected Deaths

    Time frame: For ontreatment deaths: up to maximum timeframe of 116.4 weeks for phase Ib and 92.4 weeks for phase II. For total deaths: up to 3.8 years

    On treatment deaths are reported from the start of treatment until end of study treatment plus 30 days, up to maximum duration of 116.4 weeks for phase Ib and 92.4 weeks for phase II. Deaths post treatment survival follow up are reported after the on-treatment period, up to a maximum timeframe of 46 months (3.8 years).

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

A Phase Ib/II, Open Label, Multicenter Study of MCS110 in Combination With PDR001 in Patients With Advanced Malignancies

Important dates

Study start
2016
Primary completion
2020
Study completion
2020
First posted
Jun 21, 2016
Registry last updated
Aug 11, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.