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

• ClinicalTrials.gov Identifier: NCT04731467
• Recruitment Status: Active, not recruiting
• First Posted: February 1, 2021
• Last Update Posted: April 4, 2024
• 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: April 4, 2024
• Actual Study Start Date: March 19, 2021
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 7, 2023)

• 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 C: Safety and tolerability [ Time Frame: Up to 24 months ]
  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
• Part D: Overall survival [ Time Frame: Up to 24 months ]
  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.

Original 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

Current Secondary Outcome Measures (submitted: December 18, 2022)

• 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 gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV 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 gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV 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 gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV 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 gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to 48 months ]
• Overall Survival when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV [ Time Frame: Up to 48 months ]

Original 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 ]

• 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) 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Masking Description:

Parts A and C are non-randomized parts, part D is a randomized part.

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 patients with selected recurrent or metastatic solid tumors
• 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
• 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
• 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
• 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

Study Arms

• Experimental: Part A- Dose escalation of CM24 in combination with nivolumab
  Intervention: Drug: CM-24 and Nivolumab - Dose Escalation
• Experimental: Part C- Expansion cohort of CM24 in combination with nivolumab, nab-paclitaxel and gemcitabine
  Intervention: Drug: CM-24, Nivolumab, Nab paclitaxel and Gemcitabine - Expansion
• Experimental: Part C- Expansion cohort of CM24 in combination with nivolumab and Nal-IRI/5-FU/LV
  Intervention: Drug: CM-24, Nivolumab, and Nal-IRI/5-FU/LV - Expansion
• Experimental: Part D- Expansion cohort of CM24 in combination with nivolumab, nab-paclitaxel and gemcitabine
  Intervention: Drug: CM-24, Nivolumab, Nab paclitaxel and Gemcitabine - Expansion
• Experimental: Part D- Expansion cohort of CM24 in combination with nivolumab and Nal-IRI/5-FU/LV
  Intervention: Drug: CM-24, Nivolumab, and Nal-IRI/5-FU/LV - Expansion
• Active Comparator: Part D- Expansion cohort of nivolumab in combination with nab-paclitaxel and gemcitabine
  Intervention: Drug: Nivolumab, Nab paclitaxel and Gemcitabine - Expansion
• Active Comparator: Part D- Expansion cohort of nivolumab in combination with Nal-IRI/5-FU/LV
  Intervention: Drug: Nivolumab and Nal-IRI/5-FU/LV - Expansion

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: December 18, 2022): 79
• Original Estimated Enrollment (submitted: January 28, 2021): 74
• Estimated Study Completion Date: January 2025
• Estimated Primary Completion Date: December 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); 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Israel, Spain, 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

• Current Responsible Party: Purple Biotech Ltd. ( Famewave Ltd. )
• Original Responsible Party: Same as current
• Current Study Sponsor: Famewave Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Bristol-Myers Squibb

Investigators

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

• PRS Account: Purple Biotech Ltd.
• Verification Date: April 2024