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

• ClinicalTrials.gov Identifier: NCT04731467
• Recruitment Status: Recruiting
• First Posted: February 1, 2021
• Last Update Posted: March 29, 2021
• Sponsor: Famewave Ltd.
• Collaborator: Bristol-Myers Squibb
• Information provided by (Responsible Party): Purple Biotech Ltd. ( Famewave Ltd. )

Tracking Information

• First Submitted Date: January 24, 2021
• First Posted Date: February 1, 2021
• Last Update Posted Date: March 29, 2021
• Actual Study Start Date: March 19, 2021
• Estimated Primary Completion Date: February 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 28, 2021)

• Part A: Incidence of treatment emergent adverse events [ Time Frame: Up to 24 months ]
  Incidence of treatment emergent adverse events with CM-24 and nivolumab in adults with selected recurrent or metastatic solid tumors
• Part B: Objective Response Rate [ Time Frame: Up to 24 months ]
  Objective Response Rate when phase 2 dose of CM-24 is used in combination with nivolumab in adults with recurrent and/or metastatic non-small cell lung cancer
• Part C: Objective Response Rate [ Time Frame: Up to 24 months ]
  Objective Response Rate when phase 2 dose of CM-24 is used in combination with nivolumab and nab-paclitaxel in adults with metastatic pancreatic cancer

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 28, 2021)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of CM24 in Combination With Nivolumab in Adults With Advanced Solid Tumors
• Official Title: 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
• Brief Summary: This is an open-label, multicenter, multi-dose escalation and dose expansion study in subjects with selected advanced solid tumors (Part A), advanced recurrent immune checkpoint refractory non-small cell lung cancer (NSCLC) (Part B), and metastatic pancreatic cancer (Part C) to evaluate the safety and tolerability of CM-24 in combination with nivolumab. In Part C of the study nab-paclitaxel will be administered subsequent to CM24 and nivolumab.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Solid Tumor
• Non Small Cell Lung Cancer
• Pancreatic Cancer
• Ovarian Cancer
• Papillary Thyroid Cancer
• Melanoma
• Colorectal Adenocarcinoma

Intervention

• Drug: CM-24 and Nivolumab - Dose Escalation
  Dose escalation of CM24 with nivolumab in adult subjects with selected recurrent or metastatic solid tumors
• Drug: CM-24 and Nivolumab - Expansion
  Expansion cohort of CM24 in combination with nivolumab in adult subjects with recurrent or metastatic immune checkpoint refractory non-small cell lung cancer
• Drug: CM-24, Nivolumab, and Nab paclitaxel - Expansion
  Expansion cohort of CM24 in combination with nivolumab and nab-paclitaxel in adult patients with metastatic pancreatic cancer

Study Arms

• Experimental: Dose escalation of CM24 in combination with nivolumab
  Intervention: Drug: CM-24 and Nivolumab - Dose Escalation
• Experimental: Expansion cohort of CM24 in combination with nivolumab
  Intervention: Drug: CM-24 and Nivolumab - Expansion
• Experimental: Expansion cohort of CM24 in combination with nivolumab and nab-paclitaxel
  Intervention: Drug: CM-24, Nivolumab, and Nab paclitaxel - Expansion

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 28, 2021): 74
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2024
• Estimated Primary Completion Date: February 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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);
2. Part B: Subjects with histologically confirmed metastatic or locally advanced non-small cell lung cancer (NSCLC) with documented progression following anti-PD-1/PD-L1 containing therapy; Subjects must have confirmation of progression of disease that is consistent with iCPD during or within 3 months of prior anti-PD1/PDL1 with either two radiographic scans showing disease progression or documented clinical progression (e.g., worsening of symptoms); Subjects could have had a maximum of 1 prior treatment regimen;
3. Part C: Subjects with histologically confirmed metastatic pancreatic adenocarcinoma as defined by NCCN Guidelines; Subjects with islet cell neoplasms are excluded; Subjects could have had a maximum of 1 prior treatment regimen for metastatic disease excluding nab-paclitaxel containing regimens and up to 8 weeks from last chemotherapy treatment; nab-paclitaxel completed more than 6 months prior to study is allowed.
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
2. Part B and C: Received more than 1 prior systemic regimens for the advanced/recurrent and/or metastatic disease
3. History of weight loss >10% over the 2 months prior to Screening;
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. 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;
11. Radiation within two weeks prior to the first study treatment;
12. Treatment with another investigational therapy within 30 days or 5 half-lives of the drug prior to Screening, whichever is longer;
13. 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;
14. Pregnant or lactating women.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Michael Schickler, PhD; +972 3 933 3121; trials@purple-biotech.com

Contact: Naomi Yama, RN, BSN; +972 3 933 3121; trials@purple-biotech.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04731467
• Other Study ID Numbers: FW-2020-1
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Purple Biotech Ltd. ( Famewave Ltd. )
• Study Sponsor: Famewave Ltd.
• Collaborators: Bristol-Myers Squibb

Investigators

• Study Director: Michael Schickler, PhD; Famewave Ltd.

• PRS Account: Purple Biotech Ltd.
• Verification Date: March 2021