A Study of CM24 in Combination With Nivolumab in Adults With Advanced Solid Tumors

A Phase 1/2 Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of CM24 in Combination With Nivolumab in Adults With Advanced Solid Tumors

This is an open-label, multicenter, multi-dose escalation and dose expansion study in subjects with selected advanced solid tumors (Part A) and advanced metastatic pancreatic cancer (Parts C & D) to evaluate the safety and tolerability of CM-24 in combination with nivolumab. In Part C of the study gemcitabine/nab-paclitaxel or Nal-IRI/5-FU/LV will be administered subsequent to CM24 and nivolumab. CM24, nivolumab and gemcitabine/nab-paclitaxel or Nal-IRI/5-FU/LV are administered intravenously.

Study Overview

• Status: Active, not recruiting
• Conditions: Melanoma; Pancreatic Cancer; Ovarian Cancer; Solid Tumor; Non Small Cell Lung Cancer; Colorectal Adenocarcinoma; Papillary Thyroid Cancer
• Intervention / Treatment: Drug: CM-24 and Nivolumab - Dose Escalation; Drug: CM-24, Nivolumab, Nab paclitaxel and Gemcitabine - Expansion; Drug: CM-24, Nivolumab, and Nal-IRI/5-FU/LV - Expansion; Drug: Nivolumab, Nab paclitaxel and Gemcitabine - Expansion; Drug: Nivolumab and Nal-IRI/5-FU/LV - Expansion

• Study Type: Interventional
• Enrollment (Estimated): 79
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Michael Schickler, PhD; Phone Number: +972 3 933 3121; Email: trials@purple-biotech.com
• Study Contact Backup: Name: Hadas Nachmanson; Phone Number: +972 526522552; Email: trials@purple-biotech.com

Study Locations

• Israel
  • Haifa, Israel
    • Rambam Health Care Campus
  • Ramat Gan, Israel
    • Sheba Medical Center
• Spain
  • Barcelona, Spain
    • Hospital Clínic Barcelona
  • Barcelona, Spain
    • NEXT Oncology Barcelona
  • Barcelona, Spain
    • Vall d' Hebron Institute of Oncology (VHIO)
  • Madrid, Spain
    • Hospital General Universitario Gregorio Marañón
  • Madrid, Spain
    • Clinica Universidad de Navarra
  • Madrid, Spain
    • Hospital 12 Octubre
  • Madrid, Spain
    • Hospital South Texas Accelerated Research Therapeutics (START) Madrid - CIOCC
  • Madrid, Spain
    • South Texas Accelerated Research Therapeutics (START) Madrid - Hospital Fundacion Jimenez Diaz
  • Pamplona, Spain
    • Clinica Universidad de Navarra - Pamplona
  • Pozuelo de Alarcon, Spain
    • NEXT Oncology Madrid
  • Valencia, Spain
    • Hospital Quirón Salud Valencia
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth Research Institute
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas M.D. Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Part A: Previously treated subjects with recurrent and/or metastatic NSCLC, pancreatic cancer, ovarian cancer, papillary thyroid cancer, colorectal adenocarcinoma and melanoma with documented progression/intolerance following at least one previous therapy (and not more than 2 previous regimens); Part C: Subjects with histologically confirmed advanced metastatic pancreatic adenocarcinoma as defined by NCCN Guidelines; Subjects with islet cell neoplasms are excluded; subjects with a maximum of 1 prior treatment regimen for metastatic disease excluding: nab-paclitaxel containing regimens and up to 8 weeks from last chemotherapy treatment (Arm #1); fluoropyrimidine or irinotecan containing regimens and up to 8 weeks from last chemotherapy treatment (Arm #2).

   Part C, D: Subjects with histologically confirmed advanced metastatic pancreatic adenocarcinoma as defined by NCCN Guidelines; Subjects with islet cell neoplasms are excluded.

2. Parts C, D: Subjects who have progressed on or after standard of care chemotherapy with a maximum of 1 prior treatment regimen for advanced metastatic disease:

   • Subjects enrolled in arm with gemcitabine/nab-paclitaxel combination should have received a fluoropyrimidine and/or irinotecan containing regimen in the first line of treatment; Prior gemcitabine containing regimen may be allowed only if completed at least 6 months prior to study enrollment.
   • Arm #2: Subjects enrolled in arm with Nal-IRI/5FU/LV combination should have received a gemcitabine and/or nab-paclitaxel containing regimen in the first line of treatment; Prior irinotecan and/or fluoropyrimidine containing regimens may be allowed only if completed at least 6 months prior to study enrollment.
3. Part A: Availability of an archival tumor sample prior to first treatment. Parts C, D: Fresh tumor biopsy must be obtained within 3 months prior to enrollment and after the last systemic treatment was completed.
4. Must have at least 1 measurable lesion per RECIST1.1 with progressing or new tumors since last antitumor therapy;
5. ECOG performance status score of 0 or 1;
6. Adequate safety lab results;
7. Stable brain metastases;
8. WCBP (Women of Childbearing Potential) must have a negative serum pregnancy test at Screening and a negative urine pregnancy test, WCBP must agree to abstain from sex or use an adequate method of contraception, males must abstain from sex with WCBP or use an adequate method of contraception.

Exclusion Criteria:

1. Part A: Received more than two prior systemic regimens for the metastatic disease Parts C and D: Received more than 1 prior systemic regimens for the advanced metastatic disease
2. Part A: History of weight loss >10% over the 2 months prior to Screening;
3. Unresolved AEs > Grade 1 from prior anticancer therapy.
4. Concurrent malignancy requiring treatment;
5. Active, untreated central nervous system (CNS) metastases;
6. Subjects previously treated with an anti PD-1/PD-L1 targeting agent with history immune mediated toxicity;
7. Severely immunocompromised;
8. History of allergy or hypersensitivity to any of the study treatment components;
9. Major surgery within 4 weeks of study administration;
10. Received a live / attenuated vaccine within 30 days of first treatment

11. Clinically relevant serious co-morbid medical conditions including, but not limited to:

    • Active infection;
    • Recent (within six months of Screening) cardiac disease, myocardial infarction, or severe or unstable angina;
    • History of serious arrhythmia;
    • Chronic obstructive or chronic restrictive pulmonary disease, pulmonary hypertension history of or active interstitial lung disease or pneumonitis;
    • Prior organ allograft;
    • Subjects with active, known or suspected autoimmune disease;
    • History of active or latent tuberculosis infection;
    • Positive test for HIV, HBV, or HCV;
12. Radiation within two weeks prior to the first study treatment;
13. Treatment with another investigational therapy within 30 days or 5 half-lives of the drug prior to Screening, whichever is longer;
14. Treatment with botanical preparations (e.g., herbal supplements or traditional Chinese medicines) intended for general health support or to treat the disease under study within 2 weeks prior to treatment;
15. Pregnant or lactating women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A- Dose escalation of CM24 in combination with nivolumab	Drug: CM-24 and Nivolumab - Dose Escalation; Dose escalation of CM24 with nivolumab in adult patients with selected recurrent or metastatic solid tumors
Experimental: Part C- Expansion cohort of CM24 in combination with nivolumab, nab-paclitaxel and gemcitabine	Drug: CM-24, Nivolumab, Nab paclitaxel and Gemcitabine - Expansion; Expansion cohort of CM24 in combination with nivolumab, nab-paclitaxel and gemcitabine in adult patients with advanced metastatic pancreatic cancer
Experimental: Part C- Expansion cohort of CM24 in combination with nivolumab and Nal-IRI/5-FU/LV	Drug: CM-24, Nivolumab, and Nal-IRI/5-FU/LV - Expansion; Expansion cohort of CM24 in combination with nivolumab and Nal-IRI/5-FU/LV in adult patients with advanced metastatic pancreatic cancer
Experimental: Part D- Expansion cohort of CM24 in combination with nivolumab, nab-paclitaxel and gemcitabine	Drug: CM-24, Nivolumab, Nab paclitaxel and Gemcitabine - Expansion; Expansion cohort of CM24 in combination with nivolumab, nab-paclitaxel and gemcitabine in adult patients with advanced metastatic pancreatic cancer
Experimental: Part D- Expansion cohort of CM24 in combination with nivolumab and Nal-IRI/5-FU/LV	Drug: CM-24, Nivolumab, and Nal-IRI/5-FU/LV - Expansion; Expansion cohort of CM24 in combination with nivolumab and Nal-IRI/5-FU/LV in adult patients with advanced metastatic pancreatic cancer
Active Comparator: Part D- Expansion cohort of nivolumab in combination with nab-paclitaxel and gemcitabine	Drug: Nivolumab, Nab paclitaxel and Gemcitabine - Expansion; Expansion cohort of nivolumab in combination with nab-paclitaxel and gemcitabine in adult patients with advanced metastatic pancreatic cancer
Active Comparator: Part D- Expansion cohort of nivolumab in combination with Nal-IRI/5-FU/LV	Drug: Nivolumab and Nal-IRI/5-FU/LV - Expansion; Expansion cohort of nivolumab in combination with Nal-IRI/5-FU/LV in adult patients with advanced metastatic pancreatic cancer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Incidence of treatment emergent adverse events	Incidence of treatment emergent adverse events with CM-24 and nivolumab in adults with selected recurrent or metastatic solid tumors	Up to 24 months
Part C: Safety and tolerability	Incidence of treatment emergent adverse events with CM-24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV in adults with advanced metastatic pancreatic cancer	Up to 24 months
Part D: Overall survival	This is an exploratory randomized sub-study with the objective of estimating the efficacy of CM24 and nivolumab with chemotherapy (Nal-IRI/5-FU/LV or gemcitabine/ nab-paclitaxel) and chemotherapy only (Nal- IRI/5-FU/LV or gemcitabine/nab-paclitaxel) as measured by overall survival.	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum serum concentration [Cmax]	Maximum serum concentration [Cmax] of CM24	Up to 24 months
Time of maximum concentration [Tmax]	Time of maximum concentration [Tmax] of CM24	Up to 24 months
Area under the serum concentration curve [AUC]	Area under the serum concentration curve [AUC] of CM24	Up to 24 months
Half life	Half life of CM24	Up to 24 months
Drug clearance	Drug clearance of CM24	Up to 24 months
Volume of distribution	Volume of distribution of CM24	Up to 24 months
Serum ADA parameters	Serum ADA parameters of CM24 as measured by percentage of patients who are positive for the presence of anti-drug antibodies	Up to 24 months
Objective Response Rate when CM24 is used in combination with nivolumab		Up to 24 months
Disease Control Rate when CM24 is used in combination with nivolumab		Up to 24 months
Median Duration of Response when CM24 is used in combination with nivolumab		Up to 24 months
Median Time to Response when CM24 is used in combination with nivolumab		Up to 24 months
Progression Free Survival when CM24 is used in combination with nivolumab		Up to 48 months
Overall Survival when CM24 is used in combination with nivolumab		Up to 48 months
Population pharmacokinetics when CM24 is used in combination with nivolumab as measured by the maximum plasma concentration [Cmax]		Up to 24 months
Population pharmacokinetics when CM24 is used in combination with nivolumab as measured by the average area under the concentration curve [AUC]		Up to 24 months
Population pharmacokinetics when CM24 is used in combination with nivolumab as measured by the median area under the concentration curve [AUC]		Up to 24 months
Population pharmacokinetics when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV as measured by the maximum plasma concentration [Cmax]		Up to 24 months
Population pharmacokinetics when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV as measured by the average area under the concentration curve [AUC]		Up to 24 months
Population pharmacokinetics when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV as measured by the median area under the concentration curve [AUC]		Up to 24 months
Disease Control Rate when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV		Up to 24 months
Duration of Response when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV		Up to 24 months
Time to Response when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV		Up to 24 months
Progression Free Survival when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV		Up to 48 months
Overall Survival when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV		Up to 48 months

Collaborators and Investigators

• Sponsor: Famewave Ltd.
• Collaborators: Bristol-Myers Squibb
• Investigators: Study Director: Michael Schickler, PhD, Famewave Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2021
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: January 24, 2021
• First Submitted That Met QC Criteria: January 28, 2021
• First Posted (Actual): February 1, 2021

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: nivolumab; nab-paclitaxel; Abraxane; Opdivo; CM24
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Thyroid Diseases; Head and Neck Neoplasms; Adenocarcinoma, Papillary; Thyroid Neoplasms; Thyroid Cancer, Papillary; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Paclitaxel; Fluorouracil; Nivolumab; Albumin-Bound Paclitaxel; Gemcitabine
• Other Study ID Numbers: FW-2020-1

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