Assessment of Safety, Tolerability and PK Profile of MSP008-22 in Patients With Advanced Solid Tumours

A Single Ascending Dose, Phase I Trial to Assess Safety, Tolerability and Pharmacokinetic Profile of MSP008-22 in Patients With Advanced Solid Tumours

This is the 'first-in-human' clinical trial of the Investigational Medicinal Product (IMP), Tablet formulation for Oral dosing of MSP008-22, a molecule (new chemical entity) with anticancer properties.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: MSP008-22

Detailed Description

This Single Ascending Dose (SAD) clinical trial is designed to evaluate the safety and tolerability of single oral ascending doses of the IMP in patients with Stage IV of advanced solid tumours including but not limited to Breast cancer including Triple-negative breast cancer, Ovarian cancer, Prostate cancer, Head and Neck squamous cell cancer).

The trial will also assess the pharmacokinetic (PK) profile of MSP008-22 in humans.

The safety, tolerability and PK data from this trial will determine the safety of MSP008-22 for dosing in humans in further clinical trials.

As MSP008-22 has shown efficacy in in vitro studies against various cancer cell lines and in prostate and breast cancer cell lines in xenograft studies, the first in human trial of MSP008-22 is planned in patients of 'Stage-IV of Advanced Solid Tumours (Breast cancer including Triple-negative breast cancer, Ovarian cancer, Prostate cancer, Head and Neck squamous cell cancer and other advanced solid tumors).

• Study Type: Interventional
• Enrollment (Anticipated): 27
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sangeeta Srivastava, PhD; Phone Number: 02261702100; Email: sangeeta@somaiya.com
• Study Contact Backup: Name: Deepa Arora, MD; Phone Number: 9820648395; Email: deepaarora@clinexel.com

Study Locations

• India
  • Maharashtra
    • Navi Mumbai, Maharashtra, India, 410210
      • Advanced Centre for Treatment, Research and Education in Cancer (ACTREC) of TATA Memorial Centre
      • Contact: Dr. Manjunath Nookala Krishnamurthy, MBBS, MD, DM; Phone Number: 9920703438; Email: nk.manjunath@gmail.com
      • Contact: Dr. Vikram Gota, MBBS, MD; Phone Number: 02268735130; Email: vgota@actrec.gov.in

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult patients, willing to provide written informed consent and willing to comply to trial requirements, in age range of 18-60 years (both inclusive), with stage IV - metastatic or unresectable Solid tumours (Breast cancer including TNBC, Ovarian cancer, Prostate cancer, Head and Neck squamous cell cancer).
2. Adequate bone marrow function and hepatic & Renal function
3. Has a performance status of 0 to 1 on Eastern cooperative Oncology Group (ECOG) Performance Scale and a Karnofsky Performance Status (KPS) ≥ 70
4. Adequate laboratory parameters for Haemoglobin levels, Absolute Neutrophil Count (ANC), Platelets, AST/SGOT ≤ 2.5 x ULN (≤ 5 x ULN if known liver involvement/ metastases), ALT/SGPT ≤ 2.5 x ULN (≤ 5 x ULN if known liver involvement/ metastases), Total bilirubin ≤ 1.5 x ULN (unless diagnosis of Gilbert's syndrome in which case < 3.0 times ULN), and Serum creatinine ≤ 1.5 x ULN or estimated GFR ≥ 60 mL/min
5. If male, must agree to use contraception and refrain from donating sperm during the treatment period and for ≥120 days after last dose of trial treatment.
6. If female, is not pregnant or breastfeeding, and agrees to use contraception during the treatment period and for ≥120 days after last dose of trial treatment.

Exclusion Criteria:

1. Patients who have been treated with most recent radiotherapy, immunotherapy, chemotherapy or investigational drugs within ≤10 days or 5 half-lives (whichever is shorter) from enrolment (screening), and/or who have any unresolved NCI Common Terminology Criteria of Adverse Events (CTCAE) v5.0 > Grade 1 treatment-related side effect, with the exceptions of alopecia
2. Major surgery (excluding placement of vascular access) ≤21 days from beginning of the study drug or minor surgical procedures ≤7 days.
3. Primary immunodeficiency affecting cellular immunity and active autoimmune disease with the exception of Type I Diabetes Mellitus, hypothyroidism requiring hormone replacement only, an autoimmune dermatologic condition that is managed without systemic therapy, or autoimmune arthritis that is managed without systemic therapy or documented history of autoimmune syndrome or disease.
4. Chronic medical condition that requires chronic steroid therapy or immunosuppressive medication.
5. Prior allogeneic or autologous bone marrow transplantation or other solid organ transplantation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: MSP008-22 treatment arm; Oral Escalating doses of MSP008-22- total five doses, each in form of a single dose oral formulation/tablet. Each trial participant will receive only one single oral dose of 05 identified dose levels of MSP008-22. Intra-patient dose escalation will not be carried out

Drug: MSP008-22; It is single group assignment interventional model in this clinical trial, consisting of 5 cohorts of 3 patients in each, to be enrolled such that there exists an overall gender balance for the entire trial and to also ensure including minimum five (5) patients of TNBC and minimum five (5) male patients. The trial will be initiated with dosing of a cohort of 03 patient with the Safe starting dose for MSP008-22. Dosing of the patients for the next higher dose cohort will initiate only after: (i) All 03 patients have been recruited in the lower dose Cohort and if a repeat Cohort at this dose level is recommended, another 03 patients have been recruited at same dose level (ii) all dosed patients have completed the allocated study cohort duration, (iii) safety and pharmacokinetic results have been reviewed by the Independent Dose Escalation Committee (DEC) and approved for dose escalation to next cohort.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose (MTD)	to assess Tolerability of MSP008-22 in Human	10 days post dose
Incidence of dose-limiting toxicities (DLTs)	to assess Safety of MSP008-22 in Human	10 days post-dose
Incidence of Treatment Emergent adverse events (TEAE); % of patients who experience at least 1 Treatment Emergent Adverse Event (TEAE); % of patients who discontinue due to TEAE(s).	to assess Safety of MSP008-22 in Human	30 days post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Cmax	(maximum measured concentration of MSP008-22 in plasma)	72 hours post dose
Plasma AUClast	(area under the plasma concentration time curve of MSP008-22 from hour 0 to last sample with measurable plasma concentrations)	72 hours post dose
Plasma AUCinfinity	(area under the concentration-time curve of MSP008-22 in plasma over the time interval from 0 extrapolated to infinity)	72 hours post dose
plasma tmax	(time from dosing to maximum measured concentration of MSP008-22 in plasma)	72 hours post dose
Plasma t1/2	(terminal half-life of MSP008-22 in plasma)	72 hours post dose
CL/F	(total clearance of MSP008-22 in plasma after administration estimated using formula)	72 hours post dose
Vz/F	(apparent volume of distribution of MSP008-22 during the terminal phase following administration, estimated using formula)	72 hours post dose
Ae	(the total amount of MSP008-22 excreted in urine)	72 hours post dose
Ae %dose	(the percent of MSP008-22 recovered in urine)	72 hours post dose
CLr	(and the apparent renal clearance of MSP008-22)	72 hours post dose

Collaborators and Investigators

• Sponsor: Godavari Biorefineries Limited
• Investigators: Study Director: Deepa Arora, MD, Clinexel Life Sciences Pvt. Limited

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2022
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): January 30, 2023

Study Registration Dates

• First Submitted: July 21, 2022
• First Submitted That Met QC Criteria: July 25, 2022
• First Posted (Actual): July 28, 2022

Study Record Updates

• Last Update Posted (Actual): July 28, 2022
• Last Update Submitted That Met QC Criteria: July 25, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Phase 1; First in Man; SAD; Single Ascending Dose; FIM; MSP008
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: Clinexel-GBL-002; CTRI/2022/06/043504 (Other Identifier: Clinical Trials Registry-India)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No