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

Famewave

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Solid Tumor; Colorectal Adenocarcinoma; Melanoma; Papillary Thyroid Cancer; Non Small Cell Lung Cancer; Ovarian Cancer; Pancreatic Cancer

Treatments: Drug: Nivolumab and Nal-IRI/5-FU/LV - Expansion; Drug: CM-24, Nivolumab, and Nal-IRI/5-FU/LV - Expansion; Drug: CM-24, Nivolumab, Nab paclitaxel and Gemcitabine - Expansion; Drug: CM-24 and Nivolumab - Dose Escalation; Drug: Nivolumab, Nab paclitaxel and Gemcitabine - Expansion

Study type: Interventional

Funder types: Industry

Identifiers

NCT04731467

FW-2020-1

Details and patient eligibility

About

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.

Enrollment: 79 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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79 participants in 7 patient groups

Part A- Dose escalation of CM24 in combination with nivolumab

Experimental group

Treatment:

Drug: CM-24 and Nivolumab - Dose Escalation

Part C- Expansion cohort of CM24 in combination with nivolumab, nab-paclitaxel and gemcitabine

Experimental group

Treatment:

Drug: CM-24, Nivolumab, Nab paclitaxel and Gemcitabine - Expansion

Part C- Expansion cohort of CM24 in combination with nivolumab and Nal-IRI/5-FU/LV

Experimental group

Treatment:

Drug: CM-24, Nivolumab, and Nal-IRI/5-FU/LV - Expansion

Part D- Expansion cohort of CM24 in combination with nivolumab, nab-paclitaxel and gemcitabine

Experimental group

Treatment:

Drug: CM-24, Nivolumab, Nab paclitaxel and Gemcitabine - Expansion

Part D- Expansion cohort of CM24 in combination with nivolumab and Nal-IRI/5-FU/LV

Experimental group

Treatment:

Drug: CM-24, Nivolumab, and Nal-IRI/5-FU/LV - Expansion

Part D- Expansion cohort of nivolumab in combination with nab-paclitaxel and gemcitabine

Active Comparator group

Treatment:

Drug: Nivolumab, Nab paclitaxel and Gemcitabine - Expansion

Part D- Expansion cohort of nivolumab in combination with Nal-IRI/5-FU/LV

Active Comparator group

Treatment:

Drug: Nivolumab and Nal-IRI/5-FU/LV - Expansion